Details of the Drug Combination

General Information of Drug Combination (ID: DCEE55F)

• Drug Combination Name: Pralatrexate + Topetecan
• Indication: Cutaneous melanoma; Status: Investigative [1]
• Component Drugs:
  Pralatrexate (DMAO80I): Small molecular drug
  Topetecan (DMAE6LK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SK-MEL-5
  Zero Interaction Potency (ZIP) Score: 0.35
  Bliss Independence Score: 0.71
  Loewe Additivity Score: 0.4
  LHighest Single Agent (HSA) Score: 0.27

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pralatrexate

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Peripheral T-cell lymphoma	2A90.C	Approved	[2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[3]

Pralatrexate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[5]

Pralatrexate Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Folate transporter 1 (SLC19A1)	DTOSN46	S19A1_HUMAN	Substrate	[6]
Proton-coupled folate transporter (SLC46A1)	DTDJEMI	PCFT_HUMAN	Substrate	[6]

Pralatrexate Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Folylpolyglutamate synthase (FPGS)	DECWT2V	FOLC_HUMAN	Metabolism	[7]

Indication(s) of Topetecan

Disease Entry	ICD 11	Status	REF
Small-cell lung cancer	2C25.Y	Approved	[4]

Topetecan Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase I (TOP1)	TTGTQHC	TOP1_HUMAN	Inhibitor	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Astrocytoma	DCAJ35F	SNB-19	Investigative	[9]
Renal cell carcinoma	DCQO62J	SN12C	Investigative	[9]
Invasive ductal carcinoma	DCSNVM4	T-47D	Investigative	[10]
Adenocarcinoma	DC2TVTJ	OVCAR3	Investigative	[1]
Adenocarcinoma	DCBTYYB	A549	Investigative	[1]
Adenocarcinoma	DCH78PJ	HT29	Investigative	[1]
Adenocarcinoma	DC367PT	SW-620	Investigative	[1]
Adenocarcinoma	DCAATG2	HCT-15	Investigative	[1]
Adenocarcinoma	DC1FIWA	HCT116	Investigative	[1]
Large cell lung carcinoma	DC22M4D	NCI-H460	Investigative	[1]
Malignant melanoma	DCTGGFL	UACC62	Investigative	[1]
Melanoma	DC7JHHT	SK-MEL-2	Investigative	[1]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [2] 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: 6840).
• [3] Pralatrexate FDA Label
• [4] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020671.
• [5] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [6] Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
• [7] Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.
• [8] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [9] 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.
• [10] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.