PubMed:25314077 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/25314077","sourcedb":"PubMed","sourceid":"25314077","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/25314077","text":"Cancer-selective targeting of the NF-κB survival pathway with GADD45β/MKK7 inhibitors.\nConstitutive NF-κB signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-κB-targeting strategies lack cancer cell specificity. Here, we identify the interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the GADD45β/MKK7 complex, kills MM cells effectively, and, importantly, lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher cancer cell specificity in vitro. Notably, DTP3 ablates myeloma xenografts in mice with no apparent side effects at the effective doses. Hence, cancer-selective targeting of the NF-κB pathway is possible and, at least for myeloma patients, promises a profound benefit.","tracks":[{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":86},"obj":"Sentence"},{"id":"T2","span":{"begin":87,"end":251},"obj":"Sentence"},{"id":"T3","span":{"begin":252,"end":397},"obj":"Sentence"},{"id":"T4","span":{"begin":398,"end":584},"obj":"Sentence"},{"id":"T5","span":{"begin":585,"end":722},"obj":"Sentence"},{"id":"T6","span":{"begin":723,"end":825},"obj":"Sentence"},{"id":"T7","span":{"begin":826,"end":957},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":86},"obj":"Sentence"},{"id":"T2","span":{"begin":87,"end":251},"obj":"Sentence"},{"id":"T3","span":{"begin":252,"end":397},"obj":"Sentence"},{"id":"T4","span":{"begin":398,"end":584},"obj":"Sentence"},{"id":"T5","span":{"begin":585,"end":722},"obj":"Sentence"},{"id":"T6","span":{"begin":723,"end":825},"obj":"Sentence"},{"id":"T7","span":{"begin":826,"end":957},"obj":"Sentence"}],"attributes":[{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":137,"end":153},"obj":"HP_0006775"},{"id":"T2","span":{"begin":169,"end":176},"obj":"HP_0002664"},{"id":"T3","span":{"begin":227,"end":233},"obj":"HP_0002664"},{"id":"T4","span":{"begin":689,"end":695},"obj":"HP_0002664"},{"id":"T5","span":{"begin":833,"end":839},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"},{"subj":"T4","pred":"source","obj":"PubmedHPO"},{"subj":"T5","pred":"source","obj":"PubmedHPO"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Inflammaging","color":"#ea93ec","default":true},{"id":"PubmedHPO","color":"#93ecd0"}]}]}}