Details of the Drug

General Information of Drug (ID: DMNEB6J)

Drug Name
PMID20855207C25
Synonyms GTPL8159; BDBM50329197
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) 438.6
Topological Polar Surface Area (xlogp) 3.1
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C21H26N8OS
IUPAC Name
3-[(1R)-1-[(2S,6R)-2,6-dimethylmorpholin-4-yl]ethyl]-N-[6-methyl-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine
Canonical SMILES
C[C@@H]1CN(C[C@@H](O1)C)[C@H](C)C2=NSC(=C2)NC3=NC(=CN4C3=NC=C4C5=CNN=C5)C
InChI
InChI=1S/C21H26N8OS/c1-12-9-29-18(16-6-23-24-7-16)8-22-21(29)20(25-12)26-19-5-17(27-31-19)15(4)28-10-13(2)30-14(3)11-28/h5-9,13-15H,10-11H2,1-4H3,(H,23,24)(H,25,26)/t13-,14+,15-/m1/s1
InChIKey
QBWKPGNFQQJGFY-QLFBSQMISA-N
Cross-matching ID
PubChem CID
46868971
TTD ID
D0ME9B

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Aurora B messenger RNA (AURKB mRNA) TT9RTBL AURKB_HUMAN Inhibitor [1]
Aurora kinase C (AURKC) TTLYXIT AURKC_HUMAN Inhibitor [1]
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Inhibitor [1]
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
Aurora kinase C (AURKC) DTT AURKC 2.66E-02 -0.53 -0.8
Aurora B messenger RNA (AURKB mRNA) DTT AURKB 3.85E-05 0.2 0.86
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6739-43.
2 Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
3 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.
4 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.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 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.
7 National Cancer Institute Drug Dictionary (drug id 730054).
8 Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
9 Clinical pipeline report, company report or official report of AstraZeneca (2009).
10 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.
11 Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
12 Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
13 An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted in... J Med Chem. 2007 Aug 23;50(17):4027-37.
14 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
15 A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells. ACS Med Chem Lett. 2012 Dec 13;3(12):1034-1038.
16 Discovery of a new series of Aurora inhibitors through truncation of GSK1070916. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2552-5.
17 Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27.
18 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. (Target id: 1936).
19 Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54.
20 SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
21 Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001.
22 Clinical experience with aurora kinase inhibitors: a review. Oncologist. 2009 Aug;14(8):780-93.