Details of the Drug

General Information of Drug (ID: DMAC5F2)

Drug Name
SNS-314
Synonyms SN-314
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [1]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 430.9
Topological Polar Surface Area (xlogp) 4.2
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 7
Chemical Identifiers
Formula
C18H15ClN6OS2
IUPAC Name
1-(3-chlorophenyl)-3-[5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)ethyl]-1,3-thiazol-2-yl]urea
Canonical SMILES
C1=CC(=CC(=C1)Cl)NC(=O)NC2=NC=C(S2)CCNC3=NC=NC4=C3SC=C4
InChI
InChI=1S/C18H15ClN6OS2/c19-11-2-1-3-12(8-11)24-17(26)25-18-21-9-13(28-18)4-6-20-16-15-14(5-7-27-15)22-10-23-16/h1-3,5,7-10H,4,6H2,(H,20,22,23)(H2,21,24,25,26)
InChIKey
FAYAUAZLLLJJGH-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
24995524
ChEBI ID
CHEBI:94720
CAS Number
1057249-41-8
DrugBank ID
DB06134
TTD ID
D0OA5G

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], [3], [4], [5]
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [2], [3], [4], [5]
Aurora kinase C (AURKC) TTLYXIT AURKC_HUMAN Inhibitor [2], [3], [4], [5]
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 ClinicalTrials.gov (NCT00519662) Safety and Tolerability Study of SNS-314 for Advanced Solid Tumors. U.S. National Institutes of Health.
2 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.
3 The Aurora kinase inhibitor SNS-314 shows broad therapeutic potential with chemotherapeutics and synergy with microtubule-targeted agents in a colon carcinoma model. Mol Cancer Ther. 2009 Apr;8(4):930-9.
4 Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jan-Feb;31(1):47-57.
5 Water-soluble prodrugs of an Aurora kinase inhibitor. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1409-12.
6 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.
7 A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res. 2015 Jan 15;21(2):267-73.
8 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
9 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.
10 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).
11 Clinical pipeline report, company report or official report of Cyclacel.
12 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.
13 doi: 10.1158/1535-7163.TARG-13-B281
14 Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol. 2010 Jan;136(1):99-113.
15 Effect of Aurora A kinase inhibitor MLN8237 combined with rituximab on antitumor activity in preclinical B-cell non-Hodgkin's lymphoma models. Journal of Clinical Oncology, 2009:8553.
16 Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy. Mol Cancer Ther. 2019 Dec;18(12):2207-2219.
17 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.
18 Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001.
19 Clinical experience with aurora kinase inhibitors: a review. Oncologist. 2009 Aug;14(8):780-93.
20 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.
21 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.