Details of the Drug

General Information of Drug (ID: DM0P729)

Drug Name
GSK461364
Synonyms
GSK461364; 929095-18-1; GSK-461364; 5-[6-[(4-Methyl-1-piperazinyl)methyl]-1h-benzimidazol-1-yl]-3-[(1r)-1-[2-(trifluoromethyl)phenyl]ethoxy]-2-thiophenecarboxamide; GSK 461364; UNII-8QO27TK6Q4; GSK-461364A; (R)-5-(6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazol-1-yl)-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxamide; 8QO27TK6Q4; CHEMBL1908394; GSK461364A; ZHJGWYRLJUCMRT-QGZVFWFLSA-N; SCHEMBL310080; GTPL5684; C27H28F3N5O2S; CTK8B7590; CHEBI:91333; DTXSID60239197; MolPort-016-633-304; BCP01720; GSK 461364A
Indication
Disease Entry ICD 11 Status REF
Non-hodgkin lymphoma 2B33.5 Phase 1 [1]
Solid tumour/cancer 2A00-2F9Z Phase 1 [1]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 543.6
Logarithm of the Partition Coefficient (xlogp) 4.7
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 9
Chemical Identifiers
Formula
C27H28F3N5O2S
IUPAC Name
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
Canonical SMILES
C[C@H](C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N
InChI
InChI=1S/C27H28F3N5O2S/c1-17(19-5-3-4-6-20(19)27(28,29)30)37-23-14-24(38-25(23)26(31)36)35-16-32-21-8-7-18(13-22(21)35)15-34-11-9-33(2)10-12-34/h3-8,13-14,16-17H,9-12,15H2,1-2H3,(H2,31,36)/t17-/m1/s1
InChIKey
ZHJGWYRLJUCMRT-QGZVFWFLSA-N
Cross-matching ID
PubChem CID
15983966
ChEBI ID
CHEBI:91333
CAS Number
929095-18-1
TTD ID
D08RMJ
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Polo-like kinase 1 (PLK1) TTIYVQP PLK1_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [3]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [3]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Protein Interaction/Cellular Processes [3]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Gene/Protein Processing [3]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Post-Translational Modifications [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Non-hodgkin lymphoma
ICD Disease Classification 2B33.5
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Polo-like kinase 1 (PLK1) DTT PLK1 4.16E-07 -0.38 -0.72
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5684).
2 Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
3 A specific inhibitor of polo-like kinase 1, GSK461364A, suppresses proliferation of Raji Burkitt's lymphoma cells through mediating cell cycle arrest, DNA damage, and apoptosis. Chem Biol Interact. 2020 Dec 1;332:109288. doi: 10.1016/j.cbi.2020.109288. Epub 2020 Oct 17.