Details of the Drug

General Information of Drug (ID: DM02V5Q)

Drug Name
Diamidothiazole derivative 1
Synonyms PMID26161698-Compound-53
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 409.5
Topological Polar Surface Area (xlogp) 0.6
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C19H19N7O2S
IUPAC Name
2-N-(4-piperazin-1-ylpyridin-3-yl)-4-N-pyridin-3-yl-1,3-thiazole-2,4-dicarboxamide
Canonical SMILES
C1CN(CCN1)C2=C(C=NC=C2)NC(=O)C3=NC(=CS3)C(=O)NC4=CN=CC=C4
InChI
InChI=1S/C19H19N7O2S/c27-17(23-13-2-1-4-21-10-13)15-12-29-19(25-15)18(28)24-14-11-22-5-3-16(14)26-8-6-20-7-9-26/h1-5,10-12,20H,6-9H2,(H,23,27)(H,24,28)
InChIKey
VFDWSNCXADMJQH-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
25256147
TTD ID
D0LR2Y

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Aurora kinase (AURK) TTCY4SB NOUNIPROTAC Inhibitor [1]
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Inhibitor [1]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [1]
ERK activator kinase 1 (MEK1) TTIDAPM MP2K1_HUMAN Inhibitor [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

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
Cyclin-dependent kinase 2 (CDK2) DTT CDK2 2.28E-06 0.12 0.19
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

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2 Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. Sci Transl Med. 2016 Feb 10;8(325):325ra17.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 MEK inhibitors in oncology: a patent review (2015-Present).Expert Opin Ther Pat. 2017 Aug;27(8):887-906.
5 Clinical pipeline report, company report or official report of MedKoo Biosciences.
6 Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
7 Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1). J Med Chem. 2002 Jan 17;45(2):529-32.
8 Reversine increases the plasticity of lineage-committed mammalian cells. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10482-7.
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11 Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
12 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.
13 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.
14 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.
15 National Cancer Institute Drug Dictionary (drug id 730054).
16 Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
17 Clinical pipeline report, company report or official report of AstraZeneca (2009).
18 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.
19 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
20 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
21 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.
22 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.
23 Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
24 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.
25 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.
26 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.
27 Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.