Details of the Drug

General Information of Drug (ID: DMB1IU4)

• Drug Name: Lenvatinib
• 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	N.A.	Approved	[2]
Thyroid gland papillary carcinoma	N.A.	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]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 426.9
  Logarithm of the Partition Coefficient (xlogp); 2.8
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  Half-life: The concentration or amount of drug in body reduced by one-half in 28 hours [6]
  Metabolism: The drug is metabolized via the CYP3A and aldehyde oxidase []
• Chemical Identifiers:
  Formula: C21H19ClN4O4
  IUPAC Name: 4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxyquinoline-6-carboxamide
  Canonical SMILES: COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl
  InChI: InChI=1S/C21H19ClN4O4/c1-29-19-10-17-13(9-14(19)20(23)27)18(6-7-24-17)30-12-4-5-16(15(22)8-12)26-21(28)25-11-2-3-11/h4-11H,2-3H2,1H3,(H2,23,27)(H2,25,26,28)
  InChIKey: WOSKHXYHFSIKNG-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 9823820
  ChEBI ID: CHEBI:85994
  CAS Number: 417716-92-8
  DrugBank ID: DB09078
  TTD ID: D0R0FO
  VARIDT ID: DR00265
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Thyroid cancer
• ICD Disease Classification: 2D10

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vascular endothelial growth factor receptor 2 (KDR)	DTT	KDR	1.98E-01	0.11	0.2
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Lenvatinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Lenvatinib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[8]
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Lenvatinib and Ivosidenib.	Acute myeloid leukaemia [2A60]	[9]
Arn-509	DMT81LZ	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Arn-509.	Acute myeloid leukaemia [2A60]	[10]
Gilteritinib	DMTI0ZO	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Gilteritinib.	Acute myeloid leukaemia [2A60]	[11]
Oliceridine	DM6MDCF	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Oliceridine.	Acute pain [MG31]	[12]
Ivabradine	DM0L594	Major	Increased risk of ventricular arrhythmias by the combination of Lenvatinib and Ivabradine.	Angina pectoris [BA40]	[10]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of Lenvatinib and Levalbuterol.	Asthma [CA23]	[13]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Lenvatinib and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[14]
PF-04449913	DMSB068	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[15]
Olodaterol	DM62B78	Moderate	Increased risk of ventricular arrhythmias by the combination of Lenvatinib and Olodaterol.	Chronic obstructive pulmonary disease [CA22]	[16]
Vilanterol	DMF5EK1	Moderate	Increased risk of ventricular arrhythmias by the combination of Lenvatinib and Vilanterol.	Chronic obstructive pulmonary disease [CA22]	[13]
Revefenacin	DMMP5SI	Moderate	Decreased clearance of Lenvatinib due to the transporter inhibition by Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[17]
Osilodrostat	DMIJC9X	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Osilodrostat.	Cushing syndrome [5A70]	[10]
Deutetrabenazine	DMUPFLI	Moderate	Additive CNS depression effects by the combination of Lenvatinib and Deutetrabenazine.	Dystonic disorder [8A02]	[18]
Ingrezza	DMVPLNC	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Ingrezza.	Dystonic disorder [8A02]	[19]
GS-9857	DMYU6P5	Moderate	Decreased clearance of Lenvatinib due to the transporter inhibition by GS-9857.	Hepatitis virus infection [1E50-1E51]	[20]
Fostemsavir	DM50ILT	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[21]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of ventricular arrhythmias by the combination of Lenvatinib and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[10]
Osimertinib	DMRJLAT	Major	Increased risk of prolong QT interval by the combination of Lenvatinib and Osimertinib.	Lung cancer [2C25]	[22]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Lenvatinib and Selpercatinib.	Lung cancer [2C25]	[10]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Lenvatinib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[23]
Arry-162	DM1P6FR	Moderate	Decreased clearance of Lenvatinib due to the transporter inhibition by Arry-162.	Melanoma [2C30]	[8]
LGX818	DMNQXV8	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and LGX818.	Melanoma [2C30]	[24]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of Lenvatinib and Siponimod.	Multiple sclerosis [8A40]	[8]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Lenvatinib and Ozanimod.	Multiple sclerosis [8A40]	[25]
Entrectinib	DMMPTLH	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Entrectinib.	Non-small cell lung cancer [2C25]	[8]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Rucaparib.	Ovarian cancer [2C73]	[12]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Triclabendazole.	Parasitic worm infestation [1F90]	[12]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Lenvatinib and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[26]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of Lenvatinib and Lefamulin.	Pneumonia [CA40]	[27]
Relugolix	DMK7IWL	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Relugolix.	Prostate cancer [2C82]	[10]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Lenvatinib and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[12]
Pitolisant	DM8RFNJ	Moderate	Increased risk of prolong QT interval by the combination of Lenvatinib and Pitolisant.	Somnolence [MG42]	[12]

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] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [7] 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.
• [8] Cerner Multum, Inc. "Australian Product Information.".
• [9] Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
• [10] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [11] Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
• [12] Canadian Pharmacists Association.
• [13] Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
• [14] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [15] Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [16] Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
• [17] Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
• [18] Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
• [19] Product Information. Ingrezza (valbenazine). Neurocrine Biosciences, Inc., San Diego, CA.
• [20] Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir). Gilead Sciences, Foster City, CA.
• [21] Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
• [22] Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [23] Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
• [24] Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
• [25] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
• [26] Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
• [27] Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.