Details of the Drug

General Information of Drug (ID: DMXLHIO)

• Drug Name: V158411
• Synonyms: 1174664-88-0; 1-Benzyl-N-(5-{5-[3-(Dimethylamino)-2,2-Dimethylpropoxy]-1h-Indol-2-Yl}-6-Oxo-1,6-Dihydropyridin-3-Yl)-1h-Pyrazole-4-Carboxamide; VER-00158411; 1-Benzyl-N-(5-(5-(3-(dimethylamino)-2,2-dimethylpropoxy)-1H-indol-2-yl)-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazole-4-carboxamide; VER-158411; SCHEMBL950079; BCP25319; HY-18942; CS-0014655; Q27455647; V 158411; V-158411; VER00158411; VER 00158411; VER-00158411; 1-benzyl-N-[5-[5-[3-(dimethylamino)-2,2-dimethylpropoxy]-1H-indol-2-yl]-6-oxo-1H-pyridin-3-yl]pyrazole-4-carboxamide; 5CV

Indication

Disease Entry	ICD 11	Status	REF
Triple negative breast cancer	2C60-2C65	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 538.6
  Topological Polar Surface Area (xlogp); 3.7
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C31H34N6O3
  IUPAC Name: 1-benzyl-N-[5-[5-[3-(dimethylamino)-2,2-dimethylpropoxy]-1H-indol-2-yl]-6-oxo-1H-pyridin-3-yl]pyrazole-4-carboxamide
  Canonical SMILES: CC(C)(CN(C)C)COC1=CC2=C(C=C1)NC(=C2)C3=CC(=CNC3=O)NC(=O)C4=CN(N=C4)CC5=CC=CC=C5
  InChI: InChI=1S/C31H34N6O3/c1-31(2,19-36(3)4)20-40-25-10-11-27-22(12-25)13-28(35-27)26-14-24(16-32-30(26)39)34-29(38)23-15-33-37(18-23)17-21-8-6-5-7-9-21/h5-16,18,35H,17,19-20H2,1-4H3,(H,32,39)(H,34,38)
  InChIKey: REQMZUHAMVOEON-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 44198296
  TTD ID: D3U1LH

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Triple negative breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Checkpoint kinase-1 (CHK1)	DTT	CHEK1	7.22E-191	1.43	4.74

References

• [1] Chk1 inhibition as a novel therapeutic strategy for treating triple-negative breast and ovarian cancers. BMC Cancer. 2014 Aug 7;14:570.
• [2] Cell Density Affects the Detection of Chk1 Target Engagement by the Selective Inhibitor V158411. SLAS Discov. 2018 Feb;23(2):144-153.
• [3] Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
• [4] Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening app... J Mol Graph Model. 2009 Sep;28(2):113-30.
• [5] Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] A phase Ib study of oral Chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.
• [8] National Cancer Institute Drug Dictionary (drug id 730054).
• [9] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [10] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [11] Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells. Int J Mol Sci. 2019 Aug 22;20(17):4095.
• [12] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.