Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMAC5F2)

• Drug Name: SNS-314 Drug Info
• Synonyms: SN-314

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 24995524
  ChEBI ID: CHEBI:94720
  CAS Number: CAS 1057249-41-8
  TTD Drug ID: DMAC5F2

Molecule-Related Drug Atlas

Drug(s) Targeting Aurora kinase B (AURKB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rosiglitazone + metformin	DMPIDXT	Diabetic complication	5A2Y	Phase 3	[6]
AT9283	DMQ94CT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[7]
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[8]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[9]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
CYC116	DMUMHXT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
BI-847325	DMY4B6J	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
R763	DME0CJ9	Haematological malignancy	2B33.Y	Phase 1	[14]

Drug(s) Targeting Aurora kinase A (AURKA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rosiglitazone + metformin	DMPIDXT	Diabetic complication	5A2Y	Phase 3	[6]
AT9283	DMQ94CT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[7]
MLN8237	DMO8PT9	Solid tumour/cancer	2A00-2F9Z	Phase 3	[15]
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[8]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[9]
ENMD-2076	DMJZVPB	Acute myeloid leukaemia	2A60	Phase 2	[8]
LY3295668	DM8RJTB	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[16]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
MLN8054	DMUANF3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]

Drug(s) Targeting Aurora kinase C (AURKC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[17]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[9]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
GSK1070916	DMXRPT6	Advanced solid tumour	2A00-2F9Z	Phase 1	[18]
GSK1070916A	DMCJUI9	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]
MK-6592	DMB5NOI	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[19]
Indirubin-3'-monoxime	DMLRQH0	Discovery agent	N.A.	Investigative	[20]
SU 6656	DMF1P6W	Discovery agent	N.A.	Investigative	[21]
6-bromoindirubin-3-oxime	DM12WYV	Discovery agent	N.A.	Investigative	[20]

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]

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.