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

General Information of Drug (ID: DMHOSCQ)

• Drug Name: Fruquintinib Drug Info
• Synonyms: HMPL-013

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 44480399
  CAS Number: CAS 1194506-26-7
  TTD Drug ID: DMHOSCQ

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	[4]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[5]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[6]
PI-88	DMGZPX6	Hepatocellular carcinoma	2C12.02	Phase 3	[7]
Taberminogene vadenovec	DMW5PHL	Vascular restinosis	BE2Z	Phase 3	[8]
ABT-869	DMREDYP	Solid tumour/cancer	2A00-2F9Z	Phase 3	[9]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[10]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[13]

Drug(s) Targeting Vascular endothelial growth factor receptor (VEGFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[14]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[2]
KH-902	DM8VO16	Diabetic macular edema	9B71.02	Phase 3	[15]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[16]
BAY-57-9352	DMVA5NS	Gastric adenocarcinoma	2B72	Phase 2	[17]
X-82	DMW1NKO	Age-related macular degeneration	9B75.0	Phase 2	[2]
Vorolanib	DMIM1U9	Non-small cell lung cancer	2C25	Phase 2	[18]
BFH-772	DMVUX1C	Psoriasis vulgaris	EA90	Phase 2	[19]
ASP-8477	DMBZQS7	Neuropathic pain	8E43.0	Phase 2	[20]
AG-013958	DMRET3H	Age-related macular degeneration	9B75.0	Phase 1/2	[21]

Drug(s) Targeting Vascular endothelial growth factor receptor 1 (FLT-1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[4]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[5]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[6]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
X-82	DMW1NKO	Age-related macular degeneration	9B75.0	Phase 2	[22]
OCV-101	DMT9QI2	Pancreatic cancer	2C10	Phase 2	[23]
LY3012212	DMRVEHY	Arteriosclerosis	BD40	Phase 2	[24]
OTSGC-A24	DMN0ZQ5	Colorectal cancer	2B91.Z	Phase 1/2	[25]
CEP-11981	DMYDTJ6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[26]
EW-A-401	DM3VC6T	Peripheral vascular disease	BD4Z	Phase 1	[27]

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	[28]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[29]
Regorafenib	DMHSY1I	Metastatic colorectal cancer	2B91	Approved	[30]
Sunitinib	DMCBJSR	Gastrointestinal cancer	2C11	Approved	[31]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[32]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[33]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[34]
Cabozantinib	DMIYDT4	Thyroid cancer	2D10	Approved	[35]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[4]
Lenvatinib	DMB1IU4	Thyroid cancer	2D10	Approved	[36]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vascular endothelial growth factor receptor (VEGFR)	TTVJ1D8	NOUNIPROTAC	Inhibitor	[2]
Vascular endothelial growth factor receptor 1 (FLT-1)	TT2Q6G1	VGFR1_HUMAN	Inhibitor	[3]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[3]
Vascular endothelial growth factor receptor 3 (FLT-4)	TTDCBX5	VGFR3_HUMAN	Inhibitor	[3]

References

• [1] ClinicalTrials.gov (NCT02314819) A Phase III Trial Evaluating Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients RESCO). U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] 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.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [5] 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.
• [6] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [7] Company report (Medigen)
• [8] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [9] Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006 Apr;5(4):995-1006.
• [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: 1814).
• [11] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [12] 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.
• [13] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [14] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [15] Effects of intravitreal injection of KH902, a vascular endothelial growth factor receptor decoy, on the retinas of streptozotocin-induced diabetic rats. Diabetes Obes Metab. 2012 Jul;14(7):644-53.
• [16] National Cancer Institute Drug Dictionary (drug id 452042).
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] Vorolanib, an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors: An open-label, phase I dose escalation and dose expansion trial. Chin J Cancer Res. 2021 Feb 28;33(1):103-114.
• [19] CA patent application no. 841416, Method of selecting therapeutic indications.
• [20] ClinicalTrials.gov (NCT02065349) A Study Into Pain Relief Given by ASP8477 for Peripheral Neuropathic Pain (Either Post-herpetic Neuralgia or Painful Diabetic Peripheral Neuropathy) and Its Safety. U.S. National Institutes of Health.
• [21] Receptor Tyrosine Kinase Inhibitors AG013764 and AG013711 Reduce Choroidal Neovascularization in Rat Eye. Exp Eye Res. 2007 May; 84(5): 922-933.
• [22] National Cancer Institute Drug Dictionary (drug id 695817).
• [23] Phase I trial of OTS11101, an anti-angiogenic vaccine targeting vascular endothelial growth factor receptor 1 in solid tumor.Cancer Sci.2013 Jan;104(1):98-104.
• [24] Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study. Invest New Drugs. 2014 Apr;32(2):303-11.
• [25] J Clin Oncol 33, 2015 (suppl 3; abstr 65).
• [26] 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: 8189).
• [27] DOI: http://dx.doi.org/10.1016/j.tips.2014.09.007
• [28] 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.
• [29] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [30] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [31] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [32] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [33] 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.
• [34] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [35] Clinical pipeline report, company report or official report of Exelixis (2011).
• [36] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.