PMC:7417114 / 24025-29736 JSONTXT

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(Iressa)\n(non-small cell lung cancer; EGFR) EGFR, GAK Antifibrotic (119) (116) (178) (118)\nAfatinib (Gilotrif)\n(non-small cell lung cancer, advanced squamous cell carcinoma; Her2/EGFR) EGFR, GAK Anti-inflammatory, antifibrotic (116) (178) (179)\nLapatinib (Tykerb and Tyverb)\n(breast cancer; Erb1/Erb2, EGFR) EGFR Antifibrotic (116) (178)\nOsimertinib (Tagrisso)’\n(non-small cell lung cancer; EGFR) EGFR\n(60)** AZ5104, active metabolite of osimertinib, downregulates Th17-related cytokine production via inhibition of SRC-ERK-STAT3\n(127)\nErlotinib (Tarceva)\n(non-small cell lung cancer, pancreatic cancer; Erb1, EGFR) EGFR, GAK\nKd ABL1 (310nM)\n(48) Antifibrotic (116) (178)\nNeratinib (Nerlynx)\n(breast cancer; Her2/EGFR) EGFR\nPazopanib (Votrient)\n(renal cell carcinoma, advanced soft tissue sarcoma; multi-targeted; c-KIT, FGFR, PDGFR, VEGFR) KIT Anti-inflammatory potential, antifibrotic\n(136)\nSorafenib (Nexavar)\n(renal cell carcinoma, hepatocellular carcinoma, thyroid cancer; multi-targeted; PDGFR, VEGFR, RAF) KIT, RET Antifibrotic (125) (126) (187)\nSunitinib malate (Sutent)\n(renal cell carcinoma, gastrointestinal stromal tumor; multi-targeted; PDGFR, VEGFR) AAK1, AXL, GAK, JAK1, KIT, RET Anti-inflammatory potential, cytokine suppression, antifibrotic (137) (135) (107)\nAxitinib (Inlyta)\n(renal cell carcinoma; c-KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3) ABL1, ABL2, KIT Anti-inflammatory and cytokine suppression (128)\nVandetanib (Caprelsa)\n(medullary thyroid carcinoma; EGFR, RET, VEGFR) ABL2, EGFR, GAK, RET, SRC\nKd ABL1 (270nM) (48)\nRegorafenib (Stivarga)\n(colorectal cancer, gastrointestinal stromal tumor, hepatocellular cancer; PDGFRβ, Raf-1, TIE2, VEGFR1/2/3) KIT, RET\nIbrutinib (Imbruvica)\n(mantel cell lymphoma, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, Small lymphocytic lymphoma, marginal zone lymphoma; BTK) EGFR, RET Anti-inflammatory (132) (133)\nPalbociclib (Ibrance)\n(breast cancer; CDK4, CDK6) CDK6\nAbemaciclib (Verzenio and Verzenios)\n(breast cancer, CDK4,CDK6) CDK6\nIC50 (10 nmol/L)\nCDK9\nIC50 (57 nmol/L)\n(188)** Abemaciclib in combination with anastrozole led to increased cytokine signaling and immune activation\n(189)\nAlvocidib\n(orphan drug status, acute myeloid leukemia; CDK1, CDK2, CDK4, CDK9) CDK9 Anti-inflammatory (134)\nCeritinib (Zykadia)\n(non-small cell lung cancer; ALK, IGF1R, InsR, STK22D)\nCrizotinib (Xalkori)\n(non-small cell lung cancer; ALK/ROS1) ABL1, AXL\nMasitinib (Masivet)\n(orphan drug status, potential amyotrophic lateral sclerosis drug; FAK, FGFR3, KIT, LCK, PDGFR) ABL1, KIT,\nLYN\nNintedanib (Ofev and Vargatef)\n(idiopathic pulmonary fibrosis, non-small cell lung cancer; FGFR, PDGFR, VEGFR) AAK1, ABL1, AXL, JAK2, JAK3, KIT, RET, YES1 Anti-inflammatory, cytokine suppression, antifibrotic (129) (130) (131)"}

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main therapeutic targets) Selected Kinase Target Affinity(antiviral and pulmonary benefit)KINOMEscan(kd\u003c100 nM) Anti-inflammatory activity, cytokine suppression, antifibrotic activity\nMidostaurin (Rydapt)\n(acute myeloid leukemia, systemic mastocytosis; multi-targeted; FLT3-ITD, D816V-c-KIT) AAK1, JAK2, JAK3,\nKd KIT (220nM),\nKd RET (350nM)\n(48) Anti-inflammatory and cytokine suppression (107)\nLestaurtinib\n(orphan drug status, acute myeloid leukemia; multi-targeted; FLT3, JAK2, TrkA, TrkB, TrkC) AAK1, AXL, FYN, GAK, JAK1, JAK2, JAK3, RET\nKd KIT (150nM)* Anti-inflammatory and cytokine suppression (107)\nGilteritinib (Xospata)\n(acute myeloid leukemia;\nFLT3-ITD; AXL) AXL\nIC50 (41 nM)\n(49)**\nDasatinib (Sprycel)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia; multi-targeted; BCR-ABL, SRC) ABL1, ABL2, CSK, FYN, GAK, KIT, LYN, SRC, YES Anti-inflammatory, cytokine suppression, antifibrotic (100) (99) (102) (103) (104) (101)\nImatinib Mesylate (Gleevec (US)/Glivec (Europe/Australia)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia, gastrointestinal stromal tumor, chronic eosinophilic leukemia, hypereosinophilic syndrome, systemic mastocytosis; 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Inhibitor (brand name)(indication; main therapeutic targets) Selected Kinase Target Affinity(antiviral and pulmonary benefit)KINOMEscan(kd\u003c100 nM) Anti-inflammatory activity, cytokine suppression, antifibrotic activity\nMidostaurin (Rydapt)\n(acute myeloid leukemia, systemic mastocytosis; multi-targeted; FLT3-ITD, D816V-c-KIT) AAK1, JAK2, JAK3,\nKd KIT (220nM),\nKd RET (350nM)\n(48) Anti-inflammatory and cytokine suppression (107)\nLestaurtinib\n(orphan drug status, acute myeloid leukemia; multi-targeted; FLT3, JAK2, TrkA, TrkB, TrkC) AAK1, AXL, FYN, GAK, JAK1, JAK2, JAK3, RET\nKd KIT (150nM)* Anti-inflammatory and cytokine suppression (107)\nGilteritinib (Xospata)\n(acute myeloid leukemia;\nFLT3-ITD; AXL) AXL\nIC50 (41 nM)\n(49)**\nDasatinib (Sprycel)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia; multi-targeted; BCR-ABL, SRC) ABL1, ABL2, CSK, FYN, GAK, KIT, LYN, SRC, YES Anti-inflammatory, cytokine suppression, antifibrotic (100) (99) (102) (103) (104) (101)\nImatinib Mesylate (Gleevec (US)/Glivec (Europe/Australia)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia, gastrointestinal stromal tumor, chronic eosinophilic leukemia, hypereosinophilic syndrome, systemic mastocytosis; myelodysplastic syndrome; BCR-ABL, KIT, FIP1L1-PDGFRalpha) ABL1, ABL2, KIT Anti-inflammatory, cytokine suppression/immunomodulatory, antifibrotic (91) (92) (90) (79) (94) (95) (96) (93) (77)\nNilotinib (Tasigna)\n(chronic myeloid leukemia; BCR-ABL) ABL1, ABL2, KIT Antifibrotic ((80) (81) (82) (83) (84) (85) (86)\nPonatinib (Iclusig)\n(chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia; BCR-ABL) ABL1, ABL2, KIT, RET, SRC Cytokine suppression (78)\nSaracatinib\n(orphan drug status, idiopathic pulmonary fibrosis; ABL, SRC, LCK, FGR, BLK) ABL1\nFYN, LYN, SRC, YES1\nIC50 v-ABL (30 nM); IC50 FYN (10 nM); IC50 LYN (5 nM) (isolated protein kinase assay) (186)** Antifibrotic (100) (99) (105)\nBosutinib (Bosulif)\n(chronic myeloid leukemia; ABL, SRC) ABL1, ABL2, AXL, CSK, EGFR, FYN, GAK, LYN, SRC, YES Anti-inflammatory, cytokine suppression, and antifibrotic (104) (87) (88)\nBaricitinib (Olumiant)\n(rheumatoid arthritis; JAK1, JAK2) JAK1, JAK2, TYK2\nKd AAK1 (17 nM); Kd GAK (136 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression (106) (107) (108)\nRuxolitinib (Jakafi)\n(myelofibrosis, polycythemia vera; JAK1, JAK2) GAK, JAK1, JAK2, JAK3, TYK2\nKd AAK1 (100 nM); Kd GAK (120 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, antifibrotic (107)\nFedratinib (Inrebic)\n(myelofibrosis; JAK2) AAK1, ABL1, FYN, GAK, JAK2, SRC\nKd AAK1 32 nM; Kd GAK 1 nM (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, (107) (115)\nTofacitinib (XELJANZ XR)\n(ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis; JAK1, JAK3) JAK1, JAK2, JAK3, TYK2\nNo AAK1 inhibitory activity (47) Anti-inflammatory and cytokine suppression (109) (110) (107) (111)\nGefitinib (Iressa)\n(non-small cell lung cancer; EGFR) EGFR, GAK Antifibrotic (119) (116) (178) (118)\nAfatinib (Gilotrif)\n(non-small cell lung cancer, advanced squamous cell carcinoma; Her2/EGFR) EGFR, GAK Anti-inflammatory, antifibrotic (116) (178) (179)\nLapatinib (Tykerb and Tyverb)\n(breast cancer; Erb1/Erb2, EGFR) EGFR Antifibrotic (116) (178)\nOsimertinib (Tagrisso)’\n(non-small cell lung cancer; EGFR) EGFR\n(60)** AZ5104, active metabolite of osimertinib, downregulates Th17-related cytokine production via inhibition of SRC-ERK-STAT3\n(127)\nErlotinib (Tarceva)\n(non-small cell lung cancer, pancreatic cancer; Erb1, EGFR) EGFR, GAK\nKd ABL1 (310nM)\n(48) Antifibrotic (116) (178)\nNeratinib (Nerlynx)\n(breast cancer; Her2/EGFR) EGFR\nPazopanib (Votrient)\n(renal cell carcinoma, advanced soft tissue sarcoma; multi-targeted; c-KIT, FGFR, PDGFR, VEGFR) KIT Anti-inflammatory potential, antifibrotic\n(136)\nSorafenib (Nexavar)\n(renal cell carcinoma, hepatocellular carcinoma, thyroid cancer; multi-targeted; PDGFR, VEGFR, RAF) KIT, RET Antifibrotic (125) (126) (187)\nSunitinib malate (Sutent)\n(renal cell carcinoma, gastrointestinal stromal tumor; multi-targeted; PDGFR, VEGFR) AAK1, AXL, GAK, JAK1, KIT, RET Anti-inflammatory potential, cytokine suppression, antifibrotic (137) (135) (107)\nAxitinib (Inlyta)\n(renal cell carcinoma; c-KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3) ABL1, ABL2, KIT Anti-inflammatory and cytokine suppression (128)\nVandetanib (Caprelsa)\n(medullary thyroid carcinoma; EGFR, RET, VEGFR) ABL2, EGFR, GAK, RET, SRC\nKd ABL1 (270nM) (48)\nRegorafenib (Stivarga)\n(colorectal cancer, gastrointestinal stromal tumor, hepatocellular cancer; PDGFRβ, Raf-1, TIE2, VEGFR1/2/3) KIT, RET\nIbrutinib (Imbruvica)\n(mantel cell lymphoma, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, Small lymphocytic lymphoma, marginal zone lymphoma; BTK) EGFR, RET Anti-inflammatory (132) (133)\nPalbociclib (Ibrance)\n(breast cancer; CDK4, CDK6) CDK6\nAbemaciclib (Verzenio and Verzenios)\n(breast cancer, CDK4,CDK6) CDK6\nIC50 (10 nmol/L)\nCDK9\nIC50 (57 nmol/L)\n(188)** Abemaciclib in combination with anastrozole led to increased cytokine signaling and immune activation\n(189)\nAlvocidib\n(orphan drug status, acute myeloid leukemia; CDK1, CDK2, CDK4, CDK9) CDK9 Anti-inflammatory (134)\nCeritinib (Zykadia)\n(non-small cell lung cancer; ALK, IGF1R, InsR, STK22D)\nCrizotinib (Xalkori)\n(non-small cell lung cancer; ALK/ROS1) ABL1, AXL\nMasitinib (Masivet)\n(orphan drug status, potential amyotrophic lateral sclerosis drug; FAK, FGFR3, KIT, LCK, PDGFR) ABL1, KIT,\nLYN\nNintedanib (Ofev and Vargatef)\n(idiopathic pulmonary fibrosis, non-small cell lung cancer; FGFR, PDGFR, VEGFR) AAK1, ABL1, AXL, JAK2, JAK3, KIT, RET, YES1 Anti-inflammatory, cytokine suppression, antifibrotic (129) (130) (131)"}

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Inhibitor (brand name)(indication; main therapeutic targets) Selected Kinase Target Affinity(antiviral and pulmonary benefit)KINOMEscan(kd\u003c100 nM) Anti-inflammatory activity, cytokine suppression, antifibrotic activity\nMidostaurin (Rydapt)\n(acute myeloid leukemia, systemic mastocytosis; multi-targeted; FLT3-ITD, D816V-c-KIT) AAK1, JAK2, JAK3,\nKd KIT (220nM),\nKd RET (350nM)\n(48) Anti-inflammatory and cytokine suppression (107)\nLestaurtinib\n(orphan drug status, acute myeloid leukemia; multi-targeted; FLT3, JAK2, TrkA, TrkB, TrkC) AAK1, AXL, FYN, GAK, JAK1, JAK2, JAK3, RET\nKd KIT (150nM)* Anti-inflammatory and cytokine suppression (107)\nGilteritinib (Xospata)\n(acute myeloid leukemia;\nFLT3-ITD; AXL) AXL\nIC50 (41 nM)\n(49)**\nDasatinib (Sprycel)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia; multi-targeted; BCR-ABL, SRC) ABL1, ABL2, CSK, FYN, GAK, KIT, LYN, SRC, YES Anti-inflammatory, cytokine suppression, antifibrotic (100) (99) (102) (103) (104) (101)\nImatinib Mesylate (Gleevec (US)/Glivec (Europe/Australia)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia, gastrointestinal stromal tumor, chronic eosinophilic leukemia, hypereosinophilic syndrome, systemic mastocytosis; myelodysplastic syndrome; BCR-ABL, KIT, FIP1L1-PDGFRalpha) ABL1, ABL2, KIT Anti-inflammatory, cytokine suppression/immunomodulatory, antifibrotic (91) (92) (90) (79) (94) (95) (96) (93) (77)\nNilotinib (Tasigna)\n(chronic myeloid leukemia; BCR-ABL) ABL1, ABL2, KIT Antifibrotic ((80) (81) (82) (83) (84) (85) (86)\nPonatinib (Iclusig)\n(chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia; BCR-ABL) ABL1, ABL2, KIT, RET, SRC Cytokine suppression (78)\nSaracatinib\n(orphan drug status, idiopathic pulmonary fibrosis; ABL, SRC, LCK, FGR, BLK) ABL1\nFYN, LYN, SRC, YES1\nIC50 v-ABL (30 nM); IC50 FYN (10 nM); IC50 LYN (5 nM) (isolated protein kinase assay) (186)** Antifibrotic (100) (99) (105)\nBosutinib (Bosulif)\n(chronic myeloid leukemia; ABL, SRC) ABL1, ABL2, AXL, CSK, EGFR, FYN, GAK, LYN, SRC, YES Anti-inflammatory, cytokine suppression, and antifibrotic (104) (87) (88)\nBaricitinib (Olumiant)\n(rheumatoid arthritis; JAK1, JAK2) JAK1, JAK2, TYK2\nKd AAK1 (17 nM); Kd GAK (136 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression (106) (107) (108)\nRuxolitinib (Jakafi)\n(myelofibrosis, polycythemia vera; JAK1, JAK2) GAK, JAK1, JAK2, JAK3, TYK2\nKd AAK1 (100 nM); Kd GAK (120 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, antifibrotic (107)\nFedratinib (Inrebic)\n(myelofibrosis; JAK2) AAK1, ABL1, FYN, GAK, JAK2, SRC\nKd AAK1 32 nM; Kd GAK 1 nM (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, (107) (115)\nTofacitinib (XELJANZ XR)\n(ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis; JAK1, JAK3) JAK1, JAK2, JAK3, TYK2\nNo AAK1 inhibitory activity (47) Anti-inflammatory and cytokine suppression (109) (110) (107) (111)\nGefitinib (Iressa)\n(non-small cell lung cancer; EGFR) EGFR, GAK Antifibrotic (119) (116) (178) (118)\nAfatinib (Gilotrif)\n(non-small cell lung cancer, advanced squamous cell carcinoma; Her2/EGFR) EGFR, GAK Anti-inflammatory, antifibrotic (116) (178) (179)\nLapatinib (Tykerb and Tyverb)\n(breast cancer; Erb1/Erb2, EGFR) EGFR Antifibrotic (116) (178)\nOsimertinib (Tagrisso)’\n(non-small cell lung cancer; EGFR) EGFR\n(60)** AZ5104, active metabolite of osimertinib, downregulates Th17-related cytokine production via inhibition of SRC-ERK-STAT3\n(127)\nErlotinib (Tarceva)\n(non-small cell lung cancer, pancreatic cancer; Erb1, EGFR) EGFR, GAK\nKd ABL1 (310nM)\n(48) Antifibrotic (116) (178)\nNeratinib (Nerlynx)\n(breast cancer; Her2/EGFR) EGFR\nPazopanib (Votrient)\n(renal cell carcinoma, advanced soft tissue sarcoma; multi-targeted; c-KIT, FGFR, PDGFR, VEGFR) KIT Anti-inflammatory potential, antifibrotic\n(136)\nSorafenib (Nexavar)\n(renal cell carcinoma, hepatocellular carcinoma, thyroid cancer; multi-targeted; PDGFR, VEGFR, RAF) KIT, RET Antifibrotic (125) (126) (187)\nSunitinib malate (Sutent)\n(renal cell carcinoma, gastrointestinal stromal tumor; multi-targeted; PDGFR, VEGFR) AAK1, AXL, GAK, JAK1, KIT, RET Anti-inflammatory potential, cytokine suppression, antifibrotic (137) (135) (107)\nAxitinib (Inlyta)\n(renal cell carcinoma; c-KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3) ABL1, ABL2, KIT Anti-inflammatory and cytokine suppression (128)\nVandetanib (Caprelsa)\n(medullary thyroid carcinoma; EGFR, RET, VEGFR) ABL2, EGFR, GAK, RET, SRC\nKd ABL1 (270nM) (48)\nRegorafenib (Stivarga)\n(colorectal cancer, gastrointestinal stromal tumor, hepatocellular cancer; PDGFRβ, Raf-1, TIE2, VEGFR1/2/3) KIT, RET\nIbrutinib (Imbruvica)\n(mantel cell lymphoma, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, Small lymphocytic lymphoma, marginal zone lymphoma; BTK) EGFR, RET Anti-inflammatory (132) (133)\nPalbociclib (Ibrance)\n(breast cancer; CDK4, CDK6) CDK6\nAbemaciclib (Verzenio and Verzenios)\n(breast cancer, CDK4,CDK6) CDK6\nIC50 (10 nmol/L)\nCDK9\nIC50 (57 nmol/L)\n(188)** Abemaciclib in combination with anastrozole led to increased cytokine signaling and immune activation\n(189)\nAlvocidib\n(orphan drug status, acute myeloid leukemia; CDK1, CDK2, CDK4, CDK9) CDK9 Anti-inflammatory (134)\nCeritinib (Zykadia)\n(non-small cell lung cancer; ALK, IGF1R, InsR, STK22D)\nCrizotinib (Xalkori)\n(non-small cell lung cancer; ALK/ROS1) ABL1, AXL\nMasitinib (Masivet)\n(orphan drug status, potential amyotrophic lateral sclerosis drug; FAK, FGFR3, KIT, LCK, PDGFR) ABL1, KIT,\nLYN\nNintedanib (Ofev and Vargatef)\n(idiopathic pulmonary fibrosis, non-small cell lung cancer; FGFR, PDGFR, VEGFR) AAK1, ABL1, AXL, JAK2, JAK3, KIT, RET, YES1 Anti-inflammatory, cytokine suppression, antifibrotic (129) (130) (131)"}

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Inhibitor (brand name)(indication; main therapeutic targets) Selected Kinase Target Affinity(antiviral and pulmonary benefit)KINOMEscan(kd\u003c100 nM) Anti-inflammatory activity, cytokine suppression, antifibrotic activity\nMidostaurin (Rydapt)\n(acute myeloid leukemia, systemic mastocytosis; multi-targeted; FLT3-ITD, D816V-c-KIT) AAK1, JAK2, JAK3,\nKd KIT (220nM),\nKd RET (350nM)\n(48) Anti-inflammatory and cytokine suppression (107)\nLestaurtinib\n(orphan drug status, acute myeloid leukemia; multi-targeted; FLT3, JAK2, TrkA, TrkB, TrkC) AAK1, AXL, FYN, GAK, JAK1, JAK2, JAK3, RET\nKd KIT (150nM)* Anti-inflammatory and cytokine suppression (107)\nGilteritinib (Xospata)\n(acute myeloid leukemia;\nFLT3-ITD; AXL) AXL\nIC50 (41 nM)\n(49)**\nDasatinib (Sprycel)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia; multi-targeted; BCR-ABL, SRC) ABL1, ABL2, CSK, FYN, GAK, KIT, LYN, SRC, YES Anti-inflammatory, cytokine suppression, antifibrotic (100) (99) (102) (103) (104) (101)\nImatinib Mesylate (Gleevec (US)/Glivec (Europe/Australia)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia, gastrointestinal stromal tumor, chronic eosinophilic leukemia, hypereosinophilic syndrome, systemic mastocytosis; myelodysplastic syndrome; BCR-ABL, KIT, FIP1L1-PDGFRalpha) ABL1, ABL2, KIT Anti-inflammatory, cytokine suppression/immunomodulatory, antifibrotic (91) (92) (90) (79) (94) (95) (96) (93) (77)\nNilotinib (Tasigna)\n(chronic myeloid leukemia; BCR-ABL) ABL1, ABL2, KIT Antifibrotic ((80) (81) (82) (83) (84) (85) (86)\nPonatinib (Iclusig)\n(chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia; BCR-ABL) ABL1, ABL2, KIT, RET, SRC Cytokine suppression (78)\nSaracatinib\n(orphan drug status, idiopathic pulmonary fibrosis; ABL, SRC, LCK, FGR, BLK) ABL1\nFYN, LYN, SRC, YES1\nIC50 v-ABL (30 nM); IC50 FYN (10 nM); IC50 LYN (5 nM) (isolated protein kinase assay) (186)** Antifibrotic (100) (99) (105)\nBosutinib (Bosulif)\n(chronic myeloid leukemia; ABL, SRC) ABL1, ABL2, AXL, CSK, EGFR, FYN, GAK, LYN, SRC, YES Anti-inflammatory, cytokine suppression, and antifibrotic (104) (87) (88)\nBaricitinib (Olumiant)\n(rheumatoid arthritis; JAK1, JAK2) JAK1, JAK2, TYK2\nKd AAK1 (17 nM); Kd GAK (136 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression (106) (107) (108)\nRuxolitinib (Jakafi)\n(myelofibrosis, polycythemia vera; JAK1, JAK2) GAK, JAK1, JAK2, JAK3, TYK2\nKd AAK1 (100 nM); Kd GAK (120 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, antifibrotic (107)\nFedratinib (Inrebic)\n(myelofibrosis; JAK2) AAK1, ABL1, FYN, GAK, JAK2, SRC\nKd AAK1 32 nM; Kd GAK 1 nM (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, (107) (115)\nTofacitinib (XELJANZ XR)\n(ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis; JAK1, JAK3) JAK1, JAK2, JAK3, TYK2\nNo AAK1 inhibitory activity (47) Anti-inflammatory and cytokine suppression (109) (110) (107) (111)\nGefitinib (Iressa)\n(non-small cell lung cancer; EGFR) EGFR, GAK Antifibrotic (119) (116) (178) (118)\nAfatinib (Gilotrif)\n(non-small cell lung cancer, advanced squamous cell carcinoma; Her2/EGFR) EGFR, GAK Anti-inflammatory, antifibrotic (116) (178) (179)\nLapatinib (Tykerb and Tyverb)\n(breast cancer; Erb1/Erb2, EGFR) EGFR Antifibrotic (116) (178)\nOsimertinib (Tagrisso)’\n(non-small cell lung cancer; EGFR) EGFR\n(60)** AZ5104, active metabolite of osimertinib, downregulates Th17-related cytokine production via inhibition of SRC-ERK-STAT3\n(127)\nErlotinib (Tarceva)\n(non-small cell lung cancer, pancreatic cancer; Erb1, EGFR) EGFR, GAK\nKd ABL1 (310nM)\n(48) Antifibrotic (116) (178)\nNeratinib (Nerlynx)\n(breast cancer; Her2/EGFR) EGFR\nPazopanib (Votrient)\n(renal cell carcinoma, advanced soft tissue sarcoma; multi-targeted; c-KIT, FGFR, PDGFR, VEGFR) KIT Anti-inflammatory potential, antifibrotic\n(136)\nSorafenib (Nexavar)\n(renal cell carcinoma, hepatocellular carcinoma, thyroid cancer; multi-targeted; PDGFR, VEGFR, RAF) KIT, RET Antifibrotic (125) (126) (187)\nSunitinib malate (Sutent)\n(renal cell carcinoma, gastrointestinal stromal tumor; multi-targeted; PDGFR, VEGFR) AAK1, AXL, GAK, JAK1, KIT, RET Anti-inflammatory potential, cytokine suppression, antifibrotic (137) (135) (107)\nAxitinib (Inlyta)\n(renal cell carcinoma; c-KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3) ABL1, ABL2, KIT Anti-inflammatory and cytokine suppression (128)\nVandetanib (Caprelsa)\n(medullary thyroid carcinoma; EGFR, RET, VEGFR) ABL2, EGFR, GAK, RET, SRC\nKd ABL1 (270nM) (48)\nRegorafenib (Stivarga)\n(colorectal cancer, gastrointestinal stromal tumor, hepatocellular cancer; PDGFRβ, Raf-1, TIE2, VEGFR1/2/3) KIT, RET\nIbrutinib (Imbruvica)\n(mantel cell lymphoma, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, Small lymphocytic lymphoma, marginal zone lymphoma; BTK) EGFR, RET Anti-inflammatory (132) (133)\nPalbociclib (Ibrance)\n(breast cancer; CDK4, CDK6) CDK6\nAbemaciclib (Verzenio and Verzenios)\n(breast cancer, CDK4,CDK6) CDK6\nIC50 (10 nmol/L)\nCDK9\nIC50 (57 nmol/L)\n(188)** Abemaciclib in combination with anastrozole led to increased cytokine signaling and immune activation\n(189)\nAlvocidib\n(orphan drug status, acute myeloid leukemia; CDK1, CDK2, CDK4, CDK9) CDK9 Anti-inflammatory (134)\nCeritinib (Zykadia)\n(non-small cell lung cancer; ALK, IGF1R, InsR, STK22D)\nCrizotinib (Xalkori)\n(non-small cell lung cancer; ALK/ROS1) ABL1, AXL\nMasitinib (Masivet)\n(orphan drug status, potential amyotrophic lateral sclerosis drug; FAK, FGFR3, KIT, LCK, PDGFR) ABL1, KIT,\nLYN\nNintedanib (Ofev and Vargatef)\n(idiopathic pulmonary fibrosis, non-small cell lung cancer; FGFR, PDGFR, VEGFR) AAK1, ABL1, AXL, JAK2, JAK3, KIT, RET, YES1 Anti-inflammatory, cytokine suppression, antifibrotic (129) (130) (131)"}

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Inhibitor (brand name)(indication; main therapeutic targets) Selected Kinase Target Affinity(antiviral and pulmonary benefit)KINOMEscan(kd\u003c100 nM) Anti-inflammatory activity, cytokine suppression, antifibrotic activity\nMidostaurin (Rydapt)\n(acute myeloid leukemia, systemic mastocytosis; multi-targeted; FLT3-ITD, D816V-c-KIT) AAK1, JAK2, JAK3,\nKd KIT (220nM),\nKd RET (350nM)\n(48) Anti-inflammatory and cytokine suppression (107)\nLestaurtinib\n(orphan drug status, acute myeloid leukemia; multi-targeted; FLT3, JAK2, TrkA, TrkB, TrkC) AAK1, AXL, FYN, GAK, JAK1, JAK2, JAK3, RET\nKd KIT (150nM)* Anti-inflammatory and cytokine suppression (107)\nGilteritinib (Xospata)\n(acute myeloid leukemia;\nFLT3-ITD; AXL) AXL\nIC50 (41 nM)\n(49)**\nDasatinib (Sprycel)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia; multi-targeted; BCR-ABL, SRC) ABL1, ABL2, CSK, FYN, GAK, KIT, LYN, SRC, YES Anti-inflammatory, cytokine suppression, antifibrotic (100) (99) (102) (103) (104) (101)\nImatinib Mesylate (Gleevec (US)/Glivec (Europe/Australia)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia, gastrointestinal stromal tumor, chronic eosinophilic leukemia, hypereosinophilic syndrome, systemic mastocytosis; myelodysplastic syndrome; BCR-ABL, KIT, FIP1L1-PDGFRalpha) ABL1, ABL2, KIT Anti-inflammatory, cytokine suppression/immunomodulatory, antifibrotic (91) (92) (90) (79) (94) (95) (96) (93) (77)\nNilotinib (Tasigna)\n(chronic myeloid leukemia; BCR-ABL) ABL1, ABL2, KIT Antifibrotic ((80) (81) (82) (83) (84) (85) (86)\nPonatinib (Iclusig)\n(chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia; BCR-ABL) ABL1, ABL2, KIT, RET, SRC Cytokine suppression (78)\nSaracatinib\n(orphan drug status, idiopathic pulmonary fibrosis; ABL, SRC, LCK, FGR, BLK) ABL1\nFYN, LYN, SRC, YES1\nIC50 v-ABL (30 nM); IC50 FYN (10 nM); IC50 LYN (5 nM) (isolated protein kinase assay) (186)** Antifibrotic (100) (99) (105)\nBosutinib (Bosulif)\n(chronic myeloid leukemia; ABL, SRC) ABL1, ABL2, AXL, CSK, EGFR, FYN, GAK, LYN, SRC, YES Anti-inflammatory, cytokine suppression, and antifibrotic (104) (87) (88)\nBaricitinib (Olumiant)\n(rheumatoid arthritis; JAK1, JAK2) JAK1, JAK2, TYK2\nKd AAK1 (17 nM); Kd GAK (136 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression (106) (107) (108)\nRuxolitinib (Jakafi)\n(myelofibrosis, polycythemia vera; JAK1, JAK2) GAK, JAK1, JAK2, JAK3, TYK2\nKd AAK1 (100 nM); Kd GAK (120 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, antifibrotic (107)\nFedratinib (Inrebic)\n(myelofibrosis; JAK2) AAK1, ABL1, FYN, GAK, JAK2, SRC\nKd AAK1 32 nM; Kd GAK 1 nM (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, (107) (115)\nTofacitinib (XELJANZ XR)\n(ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis; JAK1, JAK3) JAK1, JAK2, JAK3, TYK2\nNo AAK1 inhibitory activity (47) Anti-inflammatory and cytokine suppression (109) (110) (107) (111)\nGefitinib (Iressa)\n(non-small cell lung cancer; EGFR) EGFR, GAK Antifibrotic (119) (116) (178) (118)\nAfatinib (Gilotrif)\n(non-small cell lung cancer, advanced squamous cell carcinoma; Her2/EGFR) EGFR, GAK Anti-inflammatory, antifibrotic (116) (178) (179)\nLapatinib (Tykerb and Tyverb)\n(breast cancer; Erb1/Erb2, EGFR) EGFR Antifibrotic (116) (178)\nOsimertinib (Tagrisso)’\n(non-small cell lung cancer; EGFR) EGFR\n(60)** AZ5104, active metabolite of osimertinib, downregulates Th17-related cytokine production via inhibition of SRC-ERK-STAT3\n(127)\nErlotinib (Tarceva)\n(non-small cell lung cancer, pancreatic cancer; Erb1, EGFR) EGFR, GAK\nKd ABL1 (310nM)\n(48) Antifibrotic (116) (178)\nNeratinib (Nerlynx)\n(breast cancer; Her2/EGFR) EGFR\nPazopanib (Votrient)\n(renal cell carcinoma, advanced soft tissue sarcoma; multi-targeted; c-KIT, FGFR, PDGFR, VEGFR) KIT Anti-inflammatory potential, antifibrotic\n(136)\nSorafenib (Nexavar)\n(renal cell carcinoma, hepatocellular carcinoma, thyroid cancer; multi-targeted; PDGFR, VEGFR, RAF) KIT, RET Antifibrotic (125) (126) (187)\nSunitinib malate (Sutent)\n(renal cell carcinoma, gastrointestinal stromal tumor; multi-targeted; PDGFR, VEGFR) AAK1, AXL, GAK, JAK1, KIT, RET Anti-inflammatory potential, cytokine suppression, antifibrotic (137) (135) (107)\nAxitinib (Inlyta)\n(renal cell carcinoma; c-KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3) ABL1, ABL2, KIT Anti-inflammatory and cytokine suppression (128)\nVandetanib (Caprelsa)\n(medullary thyroid carcinoma; EGFR, RET, VEGFR) ABL2, EGFR, GAK, RET, SRC\nKd ABL1 (270nM) (48)\nRegorafenib (Stivarga)\n(colorectal cancer, gastrointestinal stromal tumor, hepatocellular cancer; PDGFRβ, Raf-1, TIE2, VEGFR1/2/3) KIT, RET\nIbrutinib (Imbruvica)\n(mantel cell lymphoma, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, Small lymphocytic lymphoma, marginal zone lymphoma; BTK) EGFR, RET Anti-inflammatory (132) (133)\nPalbociclib (Ibrance)\n(breast cancer; CDK4, CDK6) CDK6\nAbemaciclib (Verzenio and Verzenios)\n(breast cancer, CDK4,CDK6) CDK6\nIC50 (10 nmol/L)\nCDK9\nIC50 (57 nmol/L)\n(188)** Abemaciclib in combination with anastrozole led to increased cytokine signaling and immune activation\n(189)\nAlvocidib\n(orphan drug status, acute myeloid leukemia; CDK1, CDK2, CDK4, CDK9) CDK9 Anti-inflammatory (134)\nCeritinib (Zykadia)\n(non-small cell lung cancer; ALK, IGF1R, InsR, STK22D)\nCrizotinib (Xalkori)\n(non-small cell lung cancer; ALK/ROS1) ABL1, AXL\nMasitinib (Masivet)\n(orphan drug status, potential amyotrophic lateral sclerosis drug; FAK, FGFR3, KIT, LCK, PDGFR) ABL1, KIT,\nLYN\nNintedanib (Ofev and Vargatef)\n(idiopathic pulmonary fibrosis, non-small cell lung cancer; FGFR, PDGFR, VEGFR) AAK1, ABL1, AXL, JAK2, JAK3, KIT, RET, YES1 Anti-inflammatory, cytokine suppression, antifibrotic (129) (130) (131)"}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T73","span":{"begin":0,"end":16},"obj":"http://purl.obolibrary.org/obo/GO_0033673"},{"id":"T74","span":{"begin":1984,"end":1988},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T75","span":{"begin":2979,"end":2983},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T76","span":{"begin":2985,"end":2989},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T77","span":{"begin":3120,"end":3124},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T78","span":{"begin":3126,"end":3130},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T79","span":{"begin":3243,"end":3247},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T80","span":{"begin":3249,"end":3253},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T81","span":{"begin":3332,"end":3336},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T82","span":{"begin":3338,"end":3342},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T83","span":{"begin":3419,"end":3438},"obj":"http://purl.obolibrary.org/obo/GO_0001816"},{"id":"T84","span":{"begin":3551,"end":3555},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T85","span":{"begin":3557,"end":3561},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T86","span":{"begin":3654,"end":3658},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T87","span":{"begin":3660,"end":3664},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T88","span":{"begin":3762,"end":3766},"obj":"http://purl.obolibrary.org/obo/GO_0005007"},{"id":"T89","span":{"begin":4414,"end":4418},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T90","span":{"begin":4438,"end":4442},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T91","span":{"begin":4782,"end":4786},"obj":"http://purl.obolibrary.org/obo/GO_0005006"},{"id":"T92","span":{"begin":5063,"end":5072},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T93","span":{"begin":5576,"end":5580},"obj":"http://purl.obolibrary.org/obo/GO_0005007"}],"text":"Kinase Inhibitor (brand name)(indication; main therapeutic targets) Selected Kinase Target Affinity(antiviral and pulmonary benefit)KINOMEscan(kd\u003c100 nM) Anti-inflammatory activity, cytokine suppression, antifibrotic activity\nMidostaurin (Rydapt)\n(acute myeloid leukemia, systemic mastocytosis; multi-targeted; FLT3-ITD, D816V-c-KIT) AAK1, JAK2, JAK3,\nKd KIT (220nM),\nKd RET (350nM)\n(48) Anti-inflammatory and cytokine suppression (107)\nLestaurtinib\n(orphan drug status, acute myeloid leukemia; multi-targeted; FLT3, JAK2, TrkA, TrkB, TrkC) AAK1, AXL, FYN, GAK, JAK1, JAK2, JAK3, RET\nKd KIT (150nM)* Anti-inflammatory and cytokine suppression (107)\nGilteritinib (Xospata)\n(acute myeloid leukemia;\nFLT3-ITD; AXL) AXL\nIC50 (41 nM)\n(49)**\nDasatinib (Sprycel)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia; multi-targeted; BCR-ABL, SRC) ABL1, ABL2, CSK, FYN, GAK, KIT, LYN, SRC, YES Anti-inflammatory, cytokine suppression, antifibrotic (100) (99) (102) (103) (104) (101)\nImatinib Mesylate (Gleevec (US)/Glivec (Europe/Australia)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia, gastrointestinal stromal tumor, chronic eosinophilic leukemia, hypereosinophilic syndrome, systemic mastocytosis; myelodysplastic syndrome; BCR-ABL, KIT, FIP1L1-PDGFRalpha) ABL1, ABL2, KIT Anti-inflammatory, cytokine suppression/immunomodulatory, antifibrotic (91) (92) (90) (79) (94) (95) (96) (93) (77)\nNilotinib (Tasigna)\n(chronic myeloid leukemia; BCR-ABL) ABL1, ABL2, KIT Antifibrotic ((80) (81) (82) (83) (84) (85) (86)\nPonatinib (Iclusig)\n(chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia; BCR-ABL) ABL1, ABL2, KIT, RET, SRC Cytokine suppression (78)\nSaracatinib\n(orphan drug status, idiopathic pulmonary fibrosis; ABL, SRC, LCK, FGR, BLK) ABL1\nFYN, LYN, SRC, YES1\nIC50 v-ABL (30 nM); IC50 FYN (10 nM); IC50 LYN (5 nM) (isolated protein kinase assay) (186)** Antifibrotic (100) (99) (105)\nBosutinib (Bosulif)\n(chronic myeloid leukemia; ABL, SRC) ABL1, ABL2, AXL, CSK, EGFR, FYN, GAK, LYN, SRC, YES Anti-inflammatory, cytokine suppression, and antifibrotic (104) (87) (88)\nBaricitinib (Olumiant)\n(rheumatoid arthritis; JAK1, JAK2) JAK1, JAK2, TYK2\nKd AAK1 (17 nM); Kd GAK (136 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression (106) (107) (108)\nRuxolitinib (Jakafi)\n(myelofibrosis, polycythemia vera; JAK1, JAK2) GAK, JAK1, JAK2, JAK3, TYK2\nKd AAK1 (100 nM); Kd GAK (120 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, antifibrotic (107)\nFedratinib (Inrebic)\n(myelofibrosis; JAK2) AAK1, ABL1, FYN, GAK, JAK2, SRC\nKd AAK1 32 nM; Kd GAK 1 nM (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, (107) (115)\nTofacitinib (XELJANZ XR)\n(ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis; JAK1, JAK3) JAK1, JAK2, JAK3, TYK2\nNo AAK1 inhibitory activity (47) Anti-inflammatory and cytokine suppression (109) (110) (107) (111)\nGefitinib (Iressa)\n(non-small cell lung cancer; EGFR) EGFR, GAK Antifibrotic (119) (116) (178) (118)\nAfatinib (Gilotrif)\n(non-small cell lung cancer, advanced squamous cell carcinoma; Her2/EGFR) EGFR, GAK Anti-inflammatory, antifibrotic (116) (178) (179)\nLapatinib (Tykerb and Tyverb)\n(breast cancer; Erb1/Erb2, EGFR) EGFR Antifibrotic (116) (178)\nOsimertinib (Tagrisso)’\n(non-small cell lung cancer; EGFR) EGFR\n(60)** AZ5104, active metabolite of osimertinib, downregulates Th17-related cytokine production via inhibition of SRC-ERK-STAT3\n(127)\nErlotinib (Tarceva)\n(non-small cell lung cancer, pancreatic cancer; Erb1, EGFR) EGFR, GAK\nKd ABL1 (310nM)\n(48) Antifibrotic (116) (178)\nNeratinib (Nerlynx)\n(breast cancer; Her2/EGFR) EGFR\nPazopanib (Votrient)\n(renal cell carcinoma, advanced soft tissue sarcoma; multi-targeted; c-KIT, FGFR, PDGFR, VEGFR) KIT Anti-inflammatory potential, antifibrotic\n(136)\nSorafenib (Nexavar)\n(renal cell carcinoma, hepatocellular carcinoma, thyroid cancer; multi-targeted; PDGFR, VEGFR, RAF) KIT, RET Antifibrotic (125) (126) (187)\nSunitinib malate (Sutent)\n(renal cell carcinoma, gastrointestinal stromal tumor; multi-targeted; PDGFR, VEGFR) AAK1, AXL, GAK, JAK1, KIT, RET Anti-inflammatory potential, cytokine suppression, antifibrotic (137) (135) (107)\nAxitinib (Inlyta)\n(renal cell carcinoma; c-KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3) ABL1, ABL2, KIT Anti-inflammatory and cytokine suppression (128)\nVandetanib (Caprelsa)\n(medullary thyroid carcinoma; EGFR, RET, VEGFR) ABL2, EGFR, GAK, RET, SRC\nKd ABL1 (270nM) (48)\nRegorafenib (Stivarga)\n(colorectal cancer, gastrointestinal stromal tumor, hepatocellular cancer; PDGFRβ, Raf-1, TIE2, VEGFR1/2/3) KIT, RET\nIbrutinib (Imbruvica)\n(mantel cell lymphoma, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, Small lymphocytic lymphoma, marginal zone lymphoma; BTK) EGFR, RET Anti-inflammatory (132) (133)\nPalbociclib (Ibrance)\n(breast cancer; CDK4, CDK6) CDK6\nAbemaciclib (Verzenio and Verzenios)\n(breast cancer, CDK4,CDK6) CDK6\nIC50 (10 nmol/L)\nCDK9\nIC50 (57 nmol/L)\n(188)** Abemaciclib in combination with anastrozole led to increased cytokine signaling and immune activation\n(189)\nAlvocidib\n(orphan drug status, acute myeloid leukemia; CDK1, CDK2, CDK4, CDK9) CDK9 Anti-inflammatory (134)\nCeritinib (Zykadia)\n(non-small cell lung cancer; ALK, IGF1R, InsR, STK22D)\nCrizotinib (Xalkori)\n(non-small cell lung cancer; ALK/ROS1) ABL1, AXL\nMasitinib (Masivet)\n(orphan drug status, potential amyotrophic lateral sclerosis drug; FAK, FGFR3, KIT, LCK, PDGFR) ABL1, KIT,\nLYN\nNintedanib (Ofev and Vargatef)\n(idiopathic pulmonary fibrosis, non-small cell lung cancer; FGFR, PDGFR, VEGFR) AAK1, ABL1, AXL, JAK2, JAK3, KIT, RET, YES1 Anti-inflammatory, cytokine suppression, antifibrotic (129) (130) (131)"}

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Inhibitor (brand name)(indication; main therapeutic targets) Selected Kinase Target Affinity(antiviral and pulmonary benefit)KINOMEscan(kd\u003c100 nM) Anti-inflammatory activity, cytokine suppression, antifibrotic activity\nMidostaurin (Rydapt)\n(acute myeloid leukemia, systemic mastocytosis; multi-targeted; FLT3-ITD, D816V-c-KIT) AAK1, JAK2, JAK3,\nKd KIT (220nM),\nKd RET (350nM)\n(48) Anti-inflammatory and cytokine suppression (107)\nLestaurtinib\n(orphan drug status, acute myeloid leukemia; multi-targeted; FLT3, JAK2, TrkA, TrkB, TrkC) AAK1, AXL, FYN, GAK, JAK1, JAK2, JAK3, RET\nKd KIT (150nM)* Anti-inflammatory and cytokine suppression (107)\nGilteritinib (Xospata)\n(acute myeloid leukemia;\nFLT3-ITD; AXL) AXL\nIC50 (41 nM)\n(49)**\nDasatinib (Sprycel)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia; multi-targeted; BCR-ABL, SRC) ABL1, ABL2, CSK, FYN, GAK, KIT, LYN, SRC, YES Anti-inflammatory, cytokine suppression, antifibrotic (100) (99) (102) (103) (104) (101)\nImatinib Mesylate (Gleevec (US)/Glivec (Europe/Australia)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia, gastrointestinal stromal tumor, chronic eosinophilic leukemia, hypereosinophilic syndrome, systemic mastocytosis; myelodysplastic syndrome; BCR-ABL, KIT, FIP1L1-PDGFRalpha) ABL1, ABL2, KIT Anti-inflammatory, cytokine suppression/immunomodulatory, antifibrotic (91) (92) (90) (79) (94) (95) (96) (93) (77)\nNilotinib (Tasigna)\n(chronic myeloid leukemia; BCR-ABL) ABL1, ABL2, KIT Antifibrotic ((80) (81) (82) (83) (84) (85) (86)\nPonatinib (Iclusig)\n(chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia; BCR-ABL) ABL1, ABL2, KIT, RET, SRC Cytokine suppression (78)\nSaracatinib\n(orphan drug status, idiopathic pulmonary fibrosis; ABL, SRC, LCK, FGR, BLK) ABL1\nFYN, LYN, SRC, YES1\nIC50 v-ABL (30 nM); IC50 FYN (10 nM); IC50 LYN (5 nM) (isolated protein kinase assay) (186)** Antifibrotic (100) (99) (105)\nBosutinib (Bosulif)\n(chronic myeloid leukemia; ABL, SRC) ABL1, ABL2, AXL, CSK, EGFR, FYN, GAK, LYN, SRC, YES Anti-inflammatory, cytokine suppression, and antifibrotic (104) (87) (88)\nBaricitinib (Olumiant)\n(rheumatoid arthritis; JAK1, JAK2) JAK1, JAK2, TYK2\nKd AAK1 (17 nM); Kd GAK (136 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression (106) (107) (108)\nRuxolitinib (Jakafi)\n(myelofibrosis, polycythemia vera; JAK1, JAK2) GAK, JAK1, JAK2, JAK3, TYK2\nKd AAK1 (100 nM); Kd GAK (120 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, antifibrotic (107)\nFedratinib (Inrebic)\n(myelofibrosis; JAK2) AAK1, ABL1, FYN, GAK, JAK2, SRC\nKd AAK1 32 nM; Kd GAK 1 nM (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, (107) (115)\nTofacitinib (XELJANZ XR)\n(ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis; JAK1, JAK3) JAK1, JAK2, JAK3, TYK2\nNo AAK1 inhibitory activity (47) Anti-inflammatory and cytokine suppression (109) (110) (107) (111)\nGefitinib (Iressa)\n(non-small cell lung cancer; EGFR) EGFR, GAK Antifibrotic (119) (116) (178) (118)\nAfatinib (Gilotrif)\n(non-small cell lung cancer, advanced squamous cell carcinoma; Her2/EGFR) EGFR, GAK Anti-inflammatory, antifibrotic (116) (178) (179)\nLapatinib (Tykerb and Tyverb)\n(breast cancer; Erb1/Erb2, EGFR) EGFR Antifibrotic (116) (178)\nOsimertinib (Tagrisso)’\n(non-small cell lung cancer; EGFR) EGFR\n(60)** AZ5104, active metabolite of osimertinib, downregulates Th17-related cytokine production via inhibition of SRC-ERK-STAT3\n(127)\nErlotinib (Tarceva)\n(non-small cell lung cancer, pancreatic cancer; Erb1, EGFR) EGFR, GAK\nKd ABL1 (310nM)\n(48) Antifibrotic (116) (178)\nNeratinib (Nerlynx)\n(breast cancer; Her2/EGFR) EGFR\nPazopanib (Votrient)\n(renal cell carcinoma, advanced soft tissue sarcoma; multi-targeted; c-KIT, FGFR, PDGFR, VEGFR) KIT Anti-inflammatory potential, antifibrotic\n(136)\nSorafenib (Nexavar)\n(renal cell carcinoma, hepatocellular carcinoma, thyroid cancer; multi-targeted; PDGFR, VEGFR, RAF) KIT, RET Antifibrotic (125) (126) (187)\nSunitinib malate (Sutent)\n(renal cell carcinoma, gastrointestinal stromal tumor; multi-targeted; PDGFR, VEGFR) AAK1, AXL, GAK, JAK1, KIT, RET Anti-inflammatory potential, cytokine suppression, antifibrotic (137) (135) (107)\nAxitinib (Inlyta)\n(renal cell carcinoma; c-KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3) ABL1, ABL2, KIT Anti-inflammatory and cytokine suppression (128)\nVandetanib (Caprelsa)\n(medullary thyroid carcinoma; EGFR, RET, VEGFR) ABL2, EGFR, GAK, RET, SRC\nKd ABL1 (270nM) (48)\nRegorafenib (Stivarga)\n(colorectal cancer, gastrointestinal stromal tumor, hepatocellular cancer; PDGFRβ, Raf-1, TIE2, VEGFR1/2/3) KIT, RET\nIbrutinib (Imbruvica)\n(mantel cell lymphoma, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, Small lymphocytic lymphoma, marginal zone lymphoma; BTK) EGFR, RET Anti-inflammatory (132) (133)\nPalbociclib (Ibrance)\n(breast cancer; CDK4, CDK6) CDK6\nAbemaciclib (Verzenio and Verzenios)\n(breast cancer, CDK4,CDK6) CDK6\nIC50 (10 nmol/L)\nCDK9\nIC50 (57 nmol/L)\n(188)** Abemaciclib in combination with anastrozole led to increased cytokine signaling and immune activation\n(189)\nAlvocidib\n(orphan drug status, acute myeloid leukemia; CDK1, CDK2, CDK4, CDK9) CDK9 Anti-inflammatory (134)\nCeritinib (Zykadia)\n(non-small cell lung cancer; ALK, IGF1R, InsR, STK22D)\nCrizotinib (Xalkori)\n(non-small cell lung cancer; ALK/ROS1) ABL1, AXL\nMasitinib (Masivet)\n(orphan drug status, potential amyotrophic lateral sclerosis drug; FAK, FGFR3, KIT, LCK, PDGFR) ABL1, KIT,\nLYN\nNintedanib (Ofev and Vargatef)\n(idiopathic pulmonary fibrosis, non-small cell lung cancer; FGFR, PDGFR, VEGFR) AAK1, ABL1, AXL, JAK2, JAK3, KIT, RET, YES1 Anti-inflammatory, cytokine suppression, antifibrotic (129) (130) (131)"}

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Inhibitor (brand name)(indication; main therapeutic targets) Selected Kinase Target Affinity(antiviral and pulmonary benefit)KINOMEscan(kd\u003c100 nM) Anti-inflammatory activity, cytokine suppression, antifibrotic activity\nMidostaurin (Rydapt)\n(acute myeloid leukemia, systemic mastocytosis; multi-targeted; FLT3-ITD, D816V-c-KIT) AAK1, JAK2, JAK3,\nKd KIT (220nM),\nKd RET (350nM)\n(48) Anti-inflammatory and cytokine suppression (107)\nLestaurtinib\n(orphan drug status, acute myeloid leukemia; multi-targeted; FLT3, JAK2, TrkA, TrkB, TrkC) AAK1, AXL, FYN, GAK, JAK1, JAK2, JAK3, RET\nKd KIT (150nM)* Anti-inflammatory and cytokine suppression (107)\nGilteritinib (Xospata)\n(acute myeloid leukemia;\nFLT3-ITD; AXL) AXL\nIC50 (41 nM)\n(49)**\nDasatinib (Sprycel)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia; multi-targeted; BCR-ABL, SRC) ABL1, ABL2, CSK, FYN, GAK, KIT, LYN, SRC, YES Anti-inflammatory, cytokine suppression, antifibrotic (100) (99) (102) (103) (104) (101)\nImatinib Mesylate (Gleevec (US)/Glivec (Europe/Australia)\n(chronic myeloid leukemia, Ph+acute lymphoblastic leukemia, gastrointestinal stromal tumor, chronic eosinophilic leukemia, hypereosinophilic syndrome, systemic mastocytosis; myelodysplastic syndrome; BCR-ABL, KIT, FIP1L1-PDGFRalpha) ABL1, ABL2, KIT Anti-inflammatory, cytokine suppression/immunomodulatory, antifibrotic (91) (92) (90) (79) (94) (95) (96) (93) (77)\nNilotinib (Tasigna)\n(chronic myeloid leukemia; BCR-ABL) ABL1, ABL2, KIT Antifibrotic ((80) (81) (82) (83) (84) (85) (86)\nPonatinib (Iclusig)\n(chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia; BCR-ABL) ABL1, ABL2, KIT, RET, SRC Cytokine suppression (78)\nSaracatinib\n(orphan drug status, idiopathic pulmonary fibrosis; ABL, SRC, LCK, FGR, BLK) ABL1\nFYN, LYN, SRC, YES1\nIC50 v-ABL (30 nM); IC50 FYN (10 nM); IC50 LYN (5 nM) (isolated protein kinase assay) (186)** Antifibrotic (100) (99) (105)\nBosutinib (Bosulif)\n(chronic myeloid leukemia; ABL, SRC) ABL1, ABL2, AXL, CSK, EGFR, FYN, GAK, LYN, SRC, YES Anti-inflammatory, cytokine suppression, and antifibrotic (104) (87) (88)\nBaricitinib (Olumiant)\n(rheumatoid arthritis; JAK1, JAK2) JAK1, JAK2, TYK2\nKd AAK1 (17 nM); Kd GAK (136 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression (106) (107) (108)\nRuxolitinib (Jakafi)\n(myelofibrosis, polycythemia vera; JAK1, JAK2) GAK, JAK1, JAK2, JAK3, TYK2\nKd AAK1 (100 nM); Kd GAK (120 nM) (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, antifibrotic (107)\nFedratinib (Inrebic)\n(myelofibrosis; JAK2) AAK1, ABL1, FYN, GAK, JAK2, SRC\nKd AAK1 32 nM; Kd GAK 1 nM (cell-free assay) (47)** Anti-inflammatory and cytokine suppression, (107) (115)\nTofacitinib (XELJANZ XR)\n(ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis; JAK1, JAK3) JAK1, JAK2, JAK3, TYK2\nNo AAK1 inhibitory activity (47) Anti-inflammatory and cytokine suppression (109) (110) (107) (111)\nGefitinib (Iressa)\n(non-small cell lung cancer; EGFR) EGFR, GAK Antifibrotic (119) (116) (178) (118)\nAfatinib (Gilotrif)\n(non-small cell lung cancer, advanced squamous cell carcinoma; Her2/EGFR) EGFR, GAK Anti-inflammatory, antifibrotic (116) (178) (179)\nLapatinib (Tykerb and Tyverb)\n(breast cancer; Erb1/Erb2, EGFR) EGFR Antifibrotic (116) (178)\nOsimertinib (Tagrisso)’\n(non-small cell lung cancer; EGFR) EGFR\n(60)** AZ5104, active metabolite of osimertinib, downregulates Th17-related cytokine production via inhibition of SRC-ERK-STAT3\n(127)\nErlotinib (Tarceva)\n(non-small cell lung cancer, pancreatic cancer; Erb1, EGFR) EGFR, GAK\nKd ABL1 (310nM)\n(48) Antifibrotic (116) (178)\nNeratinib (Nerlynx)\n(breast cancer; Her2/EGFR) EGFR\nPazopanib (Votrient)\n(renal cell carcinoma, advanced soft tissue sarcoma; multi-targeted; c-KIT, FGFR, PDGFR, VEGFR) KIT Anti-inflammatory potential, antifibrotic\n(136)\nSorafenib (Nexavar)\n(renal cell carcinoma, hepatocellular carcinoma, thyroid cancer; multi-targeted; PDGFR, VEGFR, RAF) KIT, RET Antifibrotic (125) (126) (187)\nSunitinib malate (Sutent)\n(renal cell carcinoma, gastrointestinal stromal tumor; multi-targeted; PDGFR, VEGFR) AAK1, AXL, GAK, JAK1, KIT, RET Anti-inflammatory potential, cytokine suppression, antifibrotic (137) (135) (107)\nAxitinib (Inlyta)\n(renal cell carcinoma; c-KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3) ABL1, ABL2, KIT Anti-inflammatory and cytokine suppression (128)\nVandetanib (Caprelsa)\n(medullary thyroid carcinoma; EGFR, RET, VEGFR) ABL2, EGFR, GAK, RET, SRC\nKd ABL1 (270nM) (48)\nRegorafenib (Stivarga)\n(colorectal cancer, gastrointestinal stromal tumor, hepatocellular cancer; PDGFRβ, Raf-1, TIE2, VEGFR1/2/3) KIT, RET\nIbrutinib (Imbruvica)\n(mantel cell lymphoma, Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, Small lymphocytic lymphoma, marginal zone lymphoma; BTK) EGFR, RET Anti-inflammatory (132) (133)\nPalbociclib (Ibrance)\n(breast cancer; CDK4, CDK6) CDK6\nAbemaciclib (Verzenio and Verzenios)\n(breast cancer, CDK4,CDK6) CDK6\nIC50 (10 nmol/L)\nCDK9\nIC50 (57 nmol/L)\n(188)** Abemaciclib in combination with anastrozole led to increased cytokine signaling and immune activation\n(189)\nAlvocidib\n(orphan drug status, acute myeloid leukemia; CDK1, CDK2, CDK4, CDK9) CDK9 Anti-inflammatory (134)\nCeritinib (Zykadia)\n(non-small cell lung cancer; ALK, IGF1R, InsR, STK22D)\nCrizotinib (Xalkori)\n(non-small cell lung cancer; ALK/ROS1) ABL1, AXL\nMasitinib (Masivet)\n(orphan drug status, potential amyotrophic lateral sclerosis drug; FAK, FGFR3, KIT, LCK, PDGFR) ABL1, KIT,\nLYN\nNintedanib (Ofev and Vargatef)\n(idiopathic pulmonary fibrosis, non-small cell lung cancer; FGFR, PDGFR, VEGFR) AAK1, ABL1, AXL, JAK2, JAK3, KIT, RET, YES1 Anti-inflammatory, cytokine suppression, antifibrotic (129) (130) (131)"}