Details of the Drug Combination

General Information of Drug Combination (ID: DC2AR02)

• Drug Combination Name: Cabazitaxel + Pralatrexate
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Pralatrexate (DMAO80I): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: NCIH23
  Zero Interaction Potency (ZIP) Score: 15.87
  Bliss Independence Score: 16.68
  Loewe Additivity Score: 14.73
  LHighest Single Agent (HSA) Score: 15.45

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cabazitaxel

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Metastatic prostate carcinoma	N.A.	Investigative	[3]

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[6]

Cabazitaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[7]

Cabazitaxel Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Affects Expression	[8]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[8]

Indication(s) of Pralatrexate

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[4]
Peripheral T-cell lymphoma	2A90.C	Approved	[4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[5]

Pralatrexate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[9]

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	[10]
Proton-coupled folate transporter (SLC46A1)	DTDJEMI	PCFT_HUMAN	Substrate	[10]

Pralatrexate Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Folylpolyglutamate synthase (FPGS)	DECWT2V	FOLC_HUMAN	Metabolism	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC1TA7I	HCC-2998	Investigative	[1]
Adenocarcinoma	DCEBD3A	HCT-15	Investigative	[1]
Adenocarcinoma	DC1ZUQH	SW-620	Investigative	[1]
Amelanotic melanoma	DC7HSAP	M14	Investigative	[1]
Amelanotic melanoma	DC1KX21	MDA-MB-435	Investigative	[1]
Astrocytoma	DCMB0K3	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCPVYO7	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DCW1L3K	TK-10	Investigative	[1]
Cutaneous melanoma	DC0WX4Q	SK-MEL-28	Investigative	[1]
Glioblastoma	DCOX79X	SNB-75	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC61SXM	OVCAR-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCNJXT8	NCI\\/ADR-RES	Investigative	[1]
Lung adenocarcinoma	DC4EP2I	HOP-62	Investigative	[1]
Lung adenocarcinoma	DC8WWHF	EKVX	Investigative	[1]
Lung adenocarcinoma	DCR42AQ	MDA-MB-231	Investigative	[1]
Malignant melanoma	DCXXU90	UACC62	Investigative	[1]
Melanoma	DCFZOG2	MALME-3M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCZTP9V	IGROV1	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCTOH5Z	SK-OV-3	Investigative	[1]
Pleural epithelioid mesothelioma	DCAHHXF	NCI-H226	Investigative	[1]
Renal cell carcinoma	DC5O6S6	UO-31	Investigative	[1]
Colon carcinoma	DCJDBPA	KM12	Investigative	[12]
Invasive ductal carcinoma	DC9PHCA	BT-549	Investigative	[12]
Invasive ductal carcinoma	DCDEG3C	T-47D	Investigative	[12]
Invasive ductal carcinoma	DCSWP76	HS 578T	Investigative	[12]

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] 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: 6798).
• [3] Cabazitaxel FDA Label
• [4] 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).
• [5] Pralatrexate FDA Label
• [6] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [7] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [8] The triphenyltin carboxylate derivative triphenylstannyl 2-(benzylcarbamoyl)benzoate impedes prostate cancer progression via modulation of Akt/FOXO3a signaling. Toxicol Appl Pharmacol. 2020 Aug 15;401:115091. doi: 10.1016/j.taap.2020.115091. Epub 2020 Jun 7.
• [9] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [10] Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
• [11] Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.
• [12] 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.