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

General Information of Drug (ID: DMB1IU4)

• Drug Name: Lenvatinib Drug Info
• Synonyms: E 7080; E-7080, E7080; 4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxy-quinoline-6-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Thyroid cancer	2D10	Approved	[1]
Thyroid gland follicular carcinoma		Approved	[2]
Thyroid gland papillary carcinoma		Approved	[2]
Hepatocellular carcinoma	2C12.02	Phase 3	[3]
Renal cell carcinoma	2C90	Phase 3	[4]
Melanoma	2C30	Phase 2	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[4]
Ovarian cancer	2C73	Phase 1	[5]
Non-small-cell lung cancer	2C25.Y	Application submitted	[4]

• Cross-matching ID:
  PubChem CID: 9823820
  ChEBI ID: CHEBI:85994
  CAS Number: CAS 417716-92-8
  TTD Drug ID: DMB1IU4
  VARIDT Drug ID: DR00265

Molecule-Related Drug Atlas

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	[7]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[8]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[9]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[10]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[11]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[13]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[14]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[15]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[16]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[17]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[18]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[19]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[20]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[19]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[19]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[21]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[19]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[5]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 208627.
• [2] Lenvatinib FDA Label
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
• [6] Influence of CYP3A4/5 and ABC transporter polymorphisms on lenvatinib plasma trough concentrations in Japanese patients with thyroid cancer. Sci Rep. 2019 Apr 1;9(1):5404.
• [7] 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.
• [8] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [10] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [11] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [12] 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.
• [13] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [14] 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.
• [15] Clinical pipeline report, company report or official report of Exelixis (2011).
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [17] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [18] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [19] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [20] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [21] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [22] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [23] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.