Details of the Drug Combination

General Information of Drug Combination (ID: DCX0WFU)

• Drug Combination Name: Lenvatinib + Daporinad
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  Lenvatinib (DMB1IU4): Small molecular drug
  Daporinad (DMCU74R): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 14.481
  Bliss Independence Score: 12.267
  Loewe Additivity Score: 0.105
  LHighest Single Agent (HSA) Score: 1.198

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	[8]

Indication(s) of Daporinad

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Phase 2	[7]

Daporinad Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Nicotinamide phosphoribosyltransferase (NAMPT)	TTD1WIG	NAMPT_HUMAN	Inhibitor	[9]

Daporinad Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Axin-1 (AXIN1)	OTRGZGZ5	AXIN1_HUMAN	Increases Expression	[10]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[10]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[10]
Nicotinate phosphoribosyltransferase (NAPRT)	OTVVN0SL	PNCB_HUMAN	Decreases Activity	[11]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [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] 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: 7745).
• [8] 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.
• [9] Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
• [10] Targeting the NAD(+) salvage pathway suppresses APC mutation-driven colorectal cancer growth and Wnt/-catenin signaling via increasing Axin level. Cell Commun Signal. 2020 Jan 31;18(1):16. doi: 10.1186/s12964-020-0513-5.
• [11] FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res. 2003 Nov 1;63(21):7436-42.