Drug General Information |
Drug ID |
D02XNW
|
Former ID |
DCL000259
|
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
|
Drug Type |
Small molecular drug
|
Indication |
Solid tumours [ICD9: 140-199, 210-229; ICD10:C00-D48]
|
Phase 2 |
[1],
[2]
|
Therapeutic Class |
Anticancer Agents
|
Company |
Vertex; Merck
|
Structure |
|
Download
2D MOL
3D MOL
|
Formula |
C23H28N8OS
|
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
|
PubChem Compound ID |
|
PubChem Substance ID |
8149119, 10318339, 14907233, 22422965, 26683796, 39475635, 46394087, 46513935, 47160775, 49645761, 50100121, 51011682, 56355104, 57364809, 85246166, 91148021, 96024966, 99436958, 103023875, 103573134, 103905648, 114002454, 118844926, 123393021, 124756118, 124756963, 124788446, 125163769, 125333975, 126584085, 126647927, 126666957, 126728331, 131465120, 134221893, 134338916, 134964437, 135196779, 135631693, 135685114, 135685412, 135685413, 135685430, 135686018, 135686019, 135686032, 135686033, 136340127, 136367731, 137185042
|
Target and Pathway |
Target(s) |
Aurora kinase A |
Target Info |
Inhibitor |
[3],
[4]
|
Lck tyrosine kinase |
Target Info |
Inhibitor |
[3],
[4]
|
Aurora kinase B |
Target Info |
Inhibitor |
[3],
[4]
|
KEGG Pathway
|
Oocyte meiosishsa04064:NF-kappa B signaling pathway
|
Osteoclast differentiation
|
Natural killer cell mediated cytotoxicity
|
T cell receptor signaling pathway
|
HTLV-I infection
|
Primary immunodeficiency
|
NetPath Pathway
|
TCR Signaling Pathway
|
IL2 Signaling Pathway
|
PANTHER Pathway
|
Parkinson disease
|
T cell activation
|
Pathway Interaction Database
|
Aurora B signaling
|
Signaling by Aurora kinases
|
Integrin-linked kinase signaling
|
PLK1 signaling events
|
Aurora A signalingnfkappabatypicalpathway:Atypical NF-kappaB pathway
|
Glypican 1 network
|
TCR signaling in naï
|
Signaling events mediated by PTP1B
|
IL12-mediated signaling events
|
Regulation of p38-alpha and p38-beta
|
TCR signaling in naï
|
Thromboxane A2 receptor signaling
|
SHP2 signaling
|
IL2-mediated signaling events
|
CXCR4-mediated signaling events
|
Class I PI3K signaling events
|
IL2 signaling events mediated by PI3K
|
amb2 Integrin signaling
|
EPHA forward signaling
|
PDGFR-beta signaling pathway
|
IL2 signaling events mediated by STAT5
|
Ephrin B reverse signaling
|
Alpha-synuclein signalingaurora_b_pathway:Aurora B signaling
|
Aurora C signaling
|
FOXM1 transcription factor network
|
Aurora A signaling
|
Reactome
|
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
|
Regulation of PLK1 Activity at G2/M TransitionR-HSA-114604:GPVI-mediated activation cascade
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PIP3 activates AKT signaling
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Regulation of KIT signaling
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Phosphorylation of CD3 and TCR zeta chains
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Translocation of ZAP-70 to Immunological synapse
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Generation of second messenger molecules
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PECAM1 interactions
|
Constitutive Signaling by Aberrant PI3K in Cancer
|
DAP12 signaling
|
CD28 co-stimulation
|
CD28 dependent PI3K/Akt signaling
|
CD28 dependent Vav1 pathway
|
CTLA4 inhibitory signaling
|
PD-1 signaling
|
Interleukin-2 signalingR-HSA-174178:APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
|
Separation of Sister Chromatids
|
Resolution of Sister Chromatid Cohesion
|
RHO GTPases Activate Formins
|
Mitotic Prometaphase
|
WikiPathways
|
EGF/EGFR Signaling Pathway
|
JAK/STAT
|
Gastric Cancer Network 1
|
Integrated Breast Cancer Pathway
|
APC/C-mediated degradation of cell cycle proteinsWP61:Notch Signaling Pathway
|
Interferon type I signaling pathways
|
IL-2 Signaling Pathway
|
Inflammatory Response Pathway
|
Signaling by SCF-KIT
|
DAP12 interactions
|
Host Interactions of HIV factors
|
PIP3 activates AKT signaling
|
T-Cell Receptor and Co-stimulatory Signaling
|
B Cell Receptor Signaling Pathway
|
TSLP Signaling Pathway
|
TCR signaling
|
Costimulation by the CD28 familyWP2757:Mitotic Metaphase and Anaphase
|
Mitotic Prometaphase
|
Regulation of Microtubule Cytoskeleton
|
miR-targeted genes in lymphocytes - TarBase
|
miR-targeted genes in epithelium - TarBase
|
APC/C-mediated degradation of cell cycle proteins
|
References |
REF 1 | Nat Med. 2004 Mar;10(3):262-7. Epub 2004 Feb 22.VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. |
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REF 2 | (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). |
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REF 3 | 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. |
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REF 4 | Essential roles of mTOR/Akt pathway in Aurora-A cell transformation. Int J Biol Sci. 2009 Jun 19;5(5):444-50. |