Details of the Drug

General Information of Drug (ID: DMS62T0)

Drug Name
Cdk1/2 inhibitor III
Synonyms
Cdk1/2 Inhibitor III; 443798-55-8; CDK 1/2 INHIBITOR; UNII-LFR1253W75; LFR1253W75; 5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE; 5-amino-N-(2,6-difluorophenyl)-3-[(4-sulfamoylphenyl)amino]-1H-1,2,4-triazole-1-carbothioamide; 5-Amino-3-((4-(aminosulfonyl)phenyl)amino)-N-(2,6-difluorophenyl)-1H-1,2,4-triazole-1-carbothioamide; 2wu6; AC1NS9OB; CHEMBL261720; GTPL5946; BDBM6878; SCHEMBL1394721; CTK8E9250; DTXSID60416209; MolPort-044-561-528; HMS3229C16; ZINC12355112; DB07664
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 425.4
Topological Polar Surface Area (xlogp) 2.2
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 10
Chemical Identifiers
Formula
C15H13F2N7O2S2
IUPAC Name
5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide
Canonical SMILES
C1=CC(=C(C(=C1)F)NC(=S)N2C(=NC(=N2)NC3=CC=C(C=C3)S(=O)(=O)N)N)F
InChI
InChI=1S/C15H13F2N7O2S2/c16-10-2-1-3-11(17)12(10)21-15(27)24-13(18)22-14(23-24)20-8-4-6-9(7-5-8)28(19,25)26/h1-7H,(H,21,27)(H2,19,25,26)(H3,18,20,22,23)
InChIKey
ARIOBGGRZJITQX-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
5330812
CAS Number
443798-47-8
DrugBank ID
DB07664
TTD ID
D07OCA

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [2]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [2]
VEGFR1 messenger RNA (VEGFR1 mRNA) TT1VAUK VGFR1_HUMAN Inhibitor [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
VEGFR1 messenger RNA (VEGFR1 mRNA) DTT FLT1 1.64E-05 0.29 0.51
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: 5946).
2 1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J Med Chem. 2005 Jun 30;48(13):4208-11.
3 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
4 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.
5 P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther. 2007 Mar;6(3):926-34.
6 Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
7 A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70.
8 Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
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10 Discovery of novel CDK1 inhibitors by combining pharmacophore modeling, QSAR analysis and in silico screening followed by in vitro bioassay. Eur J Med Chem. 2010 Sep;45(9):4316-30.
11 Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
12 Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
13 Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518.
14 Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
15 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
16 New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
17 Inhibitors of VEGF receptors-1 and -2 based on the 2-((pyridin-4-yl)ethyl)pyridine template. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1913-9.
18 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
19 2011 Pipeline of Sirna Therapeutics.
20 The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
21 Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3595-9.
22 Macrocyclic ureas as potent and selective Chk1 inhibitors: an improved synthesis, kinome profiling, structure-activity relationships, and prelimina... Bioorg Med Chem Lett. 2007 Dec 1;17(23):6593-601.
23 Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9.
24 Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents. J Med Chem. 2004 Oct 21;47(22):5367-80.