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PubMed_Structured_Abstracts

Id Subject Object Predicate Lexical cue
T1 145-1215 None denotes Ion channels play a crucial role in the cardiovascular system. Our understanding of cardiac ion channel function has improved since their first discoveries. The flow of potassium, sodium and calcium ions across cardiomyocytes is vital for regular cardiac rhythm. Blockage of these channels, delays cardiac repolarization or tend to shorten repolarization and may induce arrhythmia. Detection of drug risk by channel blockade is considered essential for drug regulators. Advanced computational models can be used as an early screen for torsadogenic potential in drug candidates. New drug candidates that are determined to not cause blockage are more likely to pass successfully through preclinical trials and not be withdrawn later from the marketplace by manufacturer. Several different approved drugs, however, can cause a distinctive polymorphic ventricular arrhythmia known as torsade de pointes (TdP), which may lead to sudden death. The objective of the present study is to review the mechanisms and computational models used to assess the risk that a drug may TdP.
T2 1228-1948 KEY POINTS denotes There is strong evidence from multiple studies that blockage of the L-type calcium current reduces risk of TdP. Blockage of sodium channels slows cardiac action potential conduction, however, not all sodium channel blocking antiarrhythmic drugs produce a significant effect, while late sodium channel block reduces TdP. Interestingly, there are some drugs that block the hERG potassium channel and therefore cause QT prolongation, but they are not associated with TdP. Recent studies confirmed the necessity of studying multiple distinctionic ion channels which are responsible for cardiac related diseases or TdP, to obtain an improved clinical TdP risk prediction of compound interactions and also for designing drugs.

Goldhamster2_Cellosaurus

Id Subject Object Predicate Lexical cue
T1 163-164 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T2 258-261 CVCL_6758|Undefined_cell_line_type|Cricetulus griseus denotes has
T3 258-261 CVCL_E689|Transformed_cell_line|Homo sapiens denotes has
T4 504-507 CVCL_E773|Transformed_cell_line|Homo sapiens denotes may
T5 660-662 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T6 660-662 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an
T7 967-968 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T8 1057-1060 CVCL_E773|Transformed_cell_line|Homo sapiens denotes may
T9 1200-1201 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T10 1207-1210 CVCL_E773|Transformed_cell_line|Homo sapiens denotes may
T11 1481-1482 CVCL_6479|Finite_cell_line|Mus musculus denotes a
T12 1853-1855 CVCL_8754|Cancer_cell_line|Homo sapiens denotes an
T13 1853-1855 CVCL_H241|Cancer_cell_line|Homo sapiens denotes an

GoldHamster

Id Subject Object Predicate Lexical cue
T1 51-55 CHEBI:23888 denotes drug
T5 66-75 8588 denotes potassium
T2 66-75 D011188 denotes potassium
T3 66-75 D011188 denotes potassium
T4 66-75 CHEBI:26216 denotes potassium
T6 77-83 CHEBI:26708 denotes sodium
T7 88-95 1895 denotes calcium
T10 88-104 D015220 denotes calcium channels
T11 120-123 CHEBI:61377 denotes TdP
T12 120-123 CHEBI:61417 denotes TdP
T13 124-143 D001145 denotes cardiac arrhythmias
T14 124-143 D001145 denotes cardiac arrhythmias
T15 185-206 UBERON:0004535 denotes cardiovascular system
T17 237-248 D007473 denotes ion channel
T21 314-323 8588 denotes potassium
T18 314-323 D011188 denotes potassium
T19 314-323 D011188 denotes potassium
T20 314-323 CHEBI:26216 denotes potassium
T22 325-331 CHEBI:26708 denotes sodium
T23 336-343 1895 denotes calcium
T26 336-348 CHEBI:39124 denotes calcium ions
T30 400-406 GO:0048511 denotes rhythm
T31 515-525 D001145 denotes arrhythmia
T32 515-525 D001145 denotes arrhythmia
T33 540-544 CHEBI:23888 denotes drug
T34 598-602 CHEBI:23888 denotes drug
T35 706-710 CHEBI:23888 denotes drug
T36 727-731 CHEBI:23888 denotes drug
T37 941-946 CHEBI:23888 denotes drugs
T38 1005-1015 D001145 denotes arrhythmia
T39 1005-1015 D001145 denotes arrhythmia
T40 1025-1043 D016171 denotes torsade de pointes
T41 1025-1043 D016171 denotes torsade de pointes
T42 1045-1048 CHEBI:61377 denotes TdP
T43 1045-1048 CHEBI:61417 denotes TdP
T44 1069-1081 D003645 denotes sudden death
T45 1069-1081 D003645 denotes sudden death
T46 1202-1206 CHEBI:23888 denotes drug
T47 1211-1214 CHEBI:61377 denotes TdP
T48 1211-1214 CHEBI:61417 denotes TdP
T49 1303-1310 1895 denotes calcium
T50 1303-1310 CHEBI:29320 denotes calcium
T51 1303-1310 CHEBI:22984 denotes calcium
T52 1335-1338 CHEBI:61377 denotes TdP
T53 1335-1338 CHEBI:61417 denotes TdP
T55 1352-1367 D015222 denotes sodium channels
T56 1382-1398 GO:0001508 denotes action potential
T58 1428-1442 D015222 denotes sodium channel
T59 1452-1472 D000889 denotes antiarrhythmic drugs
T60 1452-1472 D000889 denotes antiarrhythmic drugs
T63 1514-1528 D015222 denotes sodium channel
T64 1543-1546 CHEBI:61377 denotes TdP
T65 1543-1546 CHEBI:61417 denotes TdP
T66 1578-1583 CHEBI:23888 denotes drugs
T67 1599-1603 PR:000000791 denotes hERG
T68 1599-1603 PR:Q12809 denotes hERG
T69 1599-1603 PR:P11308 denotes hERG
T73 1604-1613 8588 denotes potassium
T74 1604-1621 D015221 denotes potassium channel
T75 1692-1695 CHEBI:61377 denotes TdP
T76 1692-1695 CHEBI:61417 denotes TdP
T78 1771-1783 D007473 denotes ion channels
T79 1771-1783 GO:0022831 denotes ion channels
T80 1838-1841 CHEBI:61377 denotes TdP
T81 1838-1841 CHEBI:61417 denotes TdP
T82 1874-1877 CHEBI:61377 denotes TdP
T83 1874-1877 CHEBI:61417 denotes TdP
T84 1942-1947 CHEBI:23888 denotes drugs