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

General Information of Drug (ID: DM752PU)

• Drug Name: MGCD516 Drug Info
• Synonyms: Sitravatinib

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[1]
Breast cancer	2C60-2C65	Phase 2	[2]
Non-small-cell lung cancer	2C25.Y	Phase 1/2	[3]

• Cross-matching ID:
  PubChem CID: 25212148
  CAS Number: CAS 1123837-84-2
  TTD Drug ID: DM752PU

Molecule-Related Drug Atlas

Drug(s) Targeting Vascular endothelial growth factor receptor 3 (FLT-4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[9]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[10]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[11]
Fruquintinib	DMHOSCQ	Solid tumour/cancer	2A00-2F9Z	Phase 3	[12]
PI-88	DMGZPX6	Hepatocellular carcinoma	2C12.02	Phase 3	[13]
Taberminogene vadenovec	DMW5PHL	Vascular restinosis	BE2Z	Phase 3	[14]
ABT-869	DMREDYP	Solid tumour/cancer	2A00-2F9Z	Phase 3	[15]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[16]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[18]

Drug(s) Targeting Proto-oncogene c-Met (MET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[19]
Cabozantinib	DMIYDT4	Thyroid cancer	2D10	Approved	[20]
Capmatinib	DMYCXKL	Non-small-cell lung cancer	2C25.Y	Approved	[21]
Tepotinib	DMUQ0E8	Non-small cell lung cancer	2C25	Approved	[22]
Amivantamab	DMZ7AMY	Non-small-cell lung cancer	2C25.Y	Phase 3	[23]
RG3638	DMTQJE0	Gastric adenocarcinoma	2B72	Phase 3	[4]
Savolitinib	DMALFKX	Renal cell carcinoma	2C90	Phase 3	[3]
Beperminogene perplasmid	DM6RWBN	Critical limb ischemia	BD4Y	Phase 3	[24]
Tivantinib	DMNVP8Q	Hepatocellular carcinoma	2C12.02	Phase 3	[25]
CMX-2043	DMPSCVY	Cardiac disease	BA00-BE2Z	Phase 2	[26]

Drug(s) Targeting Proto-oncogene c-Ret (RET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[27]
Regorafenib	DMHSY1I	Metastatic colorectal cancer	2B91	Approved	[19]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[28]
Selpercatinib	DMZR15V	Non-small-cell lung cancer	2C25.Y	Approved	[29]
Pralsetinib	DMWU0I2	Non-small-cell lung cancer	2C25.Y	Approved	[30]
CEP-32496	DMAO04B	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[3]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[31]
GSK3179106	DM2KCIP	Inflammatory bowel disease	DD72	Phase 1	[32]
BOS172738	DM9L0D8	Solid tumour/cancer	2A00-2F9Z	Phase 1	[33]

Drug(s) Targeting Protein kinase (PK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2801653	DM0KJDY	Biliary tract cancer	2C17	Phase 2	[3]
MGCD265	DMRPCF2	Non-small-cell lung cancer	2C25.Y	Phase 2	[3]
ENMD-2076	DMJZVPB	Acute myeloid leukaemia	2A60	Phase 2	[3]
RV-568	DM652CM	Asthma	CA23	Phase 2	[34]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[35]
LX-7101	DM2LYIN	Glaucoma/ocular hypertension	9C61	Phase 1/2	[36]
Cyclocreatine	DM1I7UO	Virus infection	1A24-1D9Z	Discontinued in Phase 1	[37]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[38]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[39]
Regorafenib	DMHSY1I	Metastatic colorectal cancer	2B91	Approved	[19]
Sunitinib	DMCBJSR	Gastrointestinal cancer	2C11	Approved	[40]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[41]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[28]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[42]
Cabozantinib	DMIYDT4	Thyroid cancer	2D10	Approved	[20]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[9]
Lenvatinib	DMB1IU4	Thyroid cancer	2D10	Approved	[43]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Protein kinase (PK)	TTU8W4S	NOUNIPROTAC	Inhibitor	[3]
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Inhibitor	[4]
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Inhibitor	[5]
Proto-oncogene c-Ret (RET)	TT4DXQT	RET_HUMAN	Inhibitor	[6]
Proto-oncogene c-Ret (RET)	TT4DXQT	RET_HUMAN	Inhibitor	[5]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[7]
Vascular endothelial growth factor receptor 3 (FLT-4)	TTDCBX5	VGFR3_HUMAN	Inhibitor	[8]

References

• [1] ClinicalTrials.gov (NCT04887870) Study of Sitravatinib With or Without Other Anticancer Therapies Receiving Clinical Benefit From Parent Study. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT04123704) Sitravatinib in Metastatic Breast Cancer. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 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: 1815).
• [5] Role and relevance of TrkB mutations and expression in non-small cell lung cancer. Clin Cancer Res. 2011 May 1;17(9):2638-45.
• [6] 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: 2185).
• [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: 1813).
• [8] 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: 1814).
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [10] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [11] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [12] 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.
• [13] Company report (Medigen)
• [14] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [15] Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006 Apr;5(4):995-1006.
• [16] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [17] Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9.
• [18] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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. 2020
• [22] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [23] Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.
• [24] Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
• [25] 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. (Ligand id: 7948).
• [26] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [27] Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorg Med Chem. 2010 Feb 15;18(4):1482-96.
• [28] 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.
• [29] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [30] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [31] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [32] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [33] National Cancer Institute Drug Dictionary (drug name Zeteletinib).
• [34] Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92.
• [35] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [36] Design, synthesis and biological characterization of selective LIMK inhibitors. Bioorg Med Chem Lett. 2015 Sep 15;25(18):4005-10.
• [37] Direct determination of creatine kinase equilibrium constants with creatine or cyclocreatine substrate. Biochim Biophys Acta. 1989 Oct 19;998(3):317-20.
• [38] 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.
• [39] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [40] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [41] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [42] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [43] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.