Details of the Drug

General Information of Drug (ID: DM93YKJ)

Drug Name
VX-680
Synonyms
Tozasertib; MK 0457; VX 680; VX6; L-001281814; MK-045; MK-0457; Tozasertib (USAN); VX-68; MK-0457, Tozasertib, VX680, VX-680; N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide; N-(4-(4-(3-methyl-1H-pyrazol-5-ylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide; Cyclopropanecarboxylic acid N-(4-((4-(4-methylpiperazin-1-yl)-6-(5-methyl-2H-pyrazol-3-ylamino)pyrimidin-2-yl)sulfanyl)phenyl)amide; Cyclopropane carboxylic acid{4-[4-(4-methyl-piperazin-1-yl)-6-(5-methyl-2H-pyrazol-3-ylamino)-pyrimidin-2-ylsulphanyl]-phenyl}-amide; Cyclopropanecarboxylic Acid {4-[4-(4-Methyl-Piperazin-1-Yl)-6-(5-Methyl-2h-Pyrazol-3-Ylamino)-Pyrimidin-2-Ylsulfanyl]-Phenyl}-Amide
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [1]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 464.6
Logarithm of the Partition Coefficient (xlogp) 3.4
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C23H28N8OS
IUPAC Name
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide
Canonical SMILES
CC1=CC(=NN1)NC2=CC(=NC(=N2)SC3=CC=C(C=C3)NC(=O)C4CC4)N5CCN(CC5)C
InChI
InChI=1S/C23H28N8OS/c1-15-13-20(29-28-15)25-19-14-21(31-11-9-30(2)10-12-31)27-23(26-19)33-18-7-5-17(6-8-18)24-22(32)16-3-4-16/h5-8,13-14,16H,3-4,9-12H2,1-2H3,(H,24,32)(H2,25,26,27,28,29)
InChIKey
GCIKSSRWRFVXBI-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
5494449
ChEBI ID
CHEBI:91336
CAS Number
639089-54-6
TTD ID
D02XNW
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [2]
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [2]
LCK tyrosine protein kinase (LCK) TT860QF LCK_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Aurora kinase A (AURKA) OTMX0HYT AURKA_HUMAN Post-Translational Modifications [3]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Post-Translational Modifications [4]
Histone H3-like centromeric protein A (CENPA) OT0NEJ4X CENPA_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 Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Aurora kinase A (AURKA) DTT AURKA 9.41E-46 -1.78 -2.05
Aurora kinase B (AURKB) DTT AURKB 3.52E-36 -0.82 -1.62
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: 5718).
2 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
3 Targeting aurora kinase with MK-0457 inhibits ovarian cancer growth. Clin Cancer Res. 2008 Sep 1;14(17):5437-46. doi: 10.1158/1078-0432.CCR-07-4922.
4 Cotreatment with vorinostat enhances activity of MK-0457 (VX-680) against acute and chronic myelogenous leukemia cells. Clin Cancer Res. 2008 Oct 1;14(19):6106-15. doi: 10.1158/1078-0432.CCR-08-0721.