Details of the Drug Combination

General Information of Drug Combination (ID: DCJZXID)

• Drug Combination Name: Lenvatinib + Erlotinib
• Indication: Neoplasms; Status: Phase 1 [1]
• Component Drugs:
  Lenvatinib (DMB1IU4): Small molecular drug
  Erlotinib (DMCMBHA): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lenvatinib

Disease Entry	ICD 11	Status	REF
Thyroid cancer	2D10	Approved	[2]
Thyroid gland follicular carcinoma	N.A.	Approved	[3]
Thyroid gland papillary carcinoma	N.A.	Approved	[3]
Hepatocellular carcinoma	2C12.02	Phase 3	[4]
Renal cell carcinoma	2C90	Phase 3	[5]
Melanoma	2C30	Phase 2	[4]
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[5]
Ovarian cancer	2C73	Phase 1	[6]
Non-small-cell lung cancer	2C25.Y	Application submitted	[5]

Lenvatinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[6]

Lenvatinib Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Indication(s) of Erlotinib

Disease Entry	ICD 11	Status	REF
Adrenal gland neoplasm	N.A.	Approved	[7]
Adult hepatocellular carcinoma	N.A.	Approved	[7]
Brain cancer	2A00	Approved	[7]
Esophageal disorder	N.A.	Approved	[7]
Lung cancer	2C25.0	Approved	[7]
Non-small-cell lung cancer	2C25.Y	Approved	[8]
Pancreatic adenocarcinoma	N.A.	Approved	[7]
Psoriasis	EA90	Approved	[7]
Salivary gland squamous cell carcinoma	N.A.	Approved	[7]
Pancreatic cancer	2C10	Phase 3	[8]
Colon cancer	2B90.Z	Phase 2	[8]
Ependymoma	2A00.0Y	Investigative	[7]
Neoplastic meningitis	N.A.	Investigative	[7]
Neuroblastoma	2D11.2	Investigative	[7]

Erlotinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[10]

Erlotinib Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[12]

Erlotinib Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[14]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[14]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]

Erlotinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Response	[15]

References

• [1] ClinicalTrials.gov (NCT06161558) Erlotinib in Combination With Select Tyrosine Kinase Inhibitors in Adult Patients With Advanced Solid Tumors
• [2] FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 208627.
• [3] Lenvatinib FDA Label
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
• [7] Erlotinib FDA Label
• [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. (Ligand id: 4920).
• [9] 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.
• [10] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [11] Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7.
• [12] Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009 Jan 31;61(1):26-33.
• [13] In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9.
• [14] Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
• [15] Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29.