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

General Information of Drug (ID: DMUMHXT)

• Drug Name: CYC116 Drug Info
• Synonyms: 693228-63-6; CYC-116; CYC116; CHEMBL482967; Kinome_636; 4-methyl-5-(2-(4-morpholinophenylamino)pyrimidin-4-yl)thiazol-2-amine; 4-Methyl-5-(2-((4-morpholinophenyl)amino)-pyrimidin-4-yl)thiazol-2-amine; 4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine; 4-methyl-5-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)thiazol-2-amine; 2uue; CYC 116; GPSZYOIFQZPWEJ-UHFFFAOYSA-N; 2c5t; AC1O4WKE; MLS006011244; SCHEMBL2074998; SYN1034; EX-A753; CYC-116/CYC116; MolPort-009-679-476; HMS3244O12; HMS3244P11; BCPP000273

Indication

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

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 6420138
  TTD Drug ID: DMUMHXT

Molecule-Related Drug Atlas

Drug(s) Targeting Aurora kinase B (AURKB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AT9283	DMQ94CT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[3]
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[4]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[6]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
SNS-314	DMAC5F2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
BI-847325	DMY4B6J	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
R763	DME0CJ9	Haematological malignancy	2B33.Y	Phase 1	[11]
GSK1070916	DMXRPT6	Advanced solid tumour	2A00-2F9Z	Phase 1	[12]

Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[13]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[14]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[15]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[16]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[17]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[18]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[19]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[20]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[21]

Drug(s) Targeting Aurora kinase A (AURKA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AT9283	DMQ94CT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[3]
MLN8237	DMO8PT9	Solid tumour/cancer	2A00-2F9Z	Phase 3	[22]
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[4]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[6]
ENMD-2076	DMJZVPB	Acute myeloid leukaemia	2A60	Phase 2	[4]
LY3295668	DM8RJTB	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[23]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
MLN8054	DMUANF3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]

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]
Aurora kinase B (AURKB)	TT5LS6T	AURKB_HUMAN	Inhibitor	[2]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[2]

References

• [1] ClinicalTrials.gov (NCT00560716) A Phase I Pharmacologic Study of CYC116, an Oral Aurora Kinase Inhibitor, in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of Cyclacel.
• [3] 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.
• [4] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [5] 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.
• [6] 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.
• [7] 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).
• [8] 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.
• [9] 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.
• [10] doi: 10.1158/1535-7163.TARG-13-B281
• [11] 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.
• [12] Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001.
• [13] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [14] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [16] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [17] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [18] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [19] Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
• [20] Clinical pipeline report, company report or official report of Exelixis (2011).
• [21] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [22] 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.
• [23] 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.