Details of the Drug Combination

General Information of Drug Combination (ID: DC7P54Z)

• Drug Combination Name: Cabazitaxel + SY-1425
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  SY-1425 (DMH8UF0): N.A.
• High-throughput Screening Result:
  Testing Cell Line: K-562
  Zero Interaction Potency (ZIP) Score: 12.55
  Bliss Independence Score: 7.93
  Loewe Additivity Score: 0.55
  LHighest Single Agent (HSA) Score: 10.46

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	[5]

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	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[6]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[6]

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	[7]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[7]

Indication(s) of SY-1425

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Phase 1	[4]
Myelodysplastic syndrome	2A37	Phase 1	[4]

SY-1425 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Retinoic acid receptor alpha (RARA)	TTW38KT	RARA_HUMAN	Agonist	[4]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCX1XS1	DU-145	Investigative	[1]
Adenocarcinoma	DCF5CKV	A549	Investigative	[1]
Adenocarcinoma	DCL69GJ	HT29	Investigative	[1]
Adult acute myeloid leukemia	DCVDJ6Q	HL-60(TB)	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCDXUEZ	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DC5UWNF	CAKI-1	Investigative	[1]
Cutaneous melanoma	DCSJYHZ	SK-MEL-5	Investigative	[1]
Glioma	DCUYL3N	SF-539	Investigative	[1]
Large cell lung carcinoma	DC3JC4U	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC3HIHL	NCI-H522	Investigative	[1]
Malignant melanoma	DCD82CM	UACC62	Investigative	[1]
Malignant melanoma	DCK05N1	LOX IMVI	Investigative	[1]
Melanoma	DC8AXGT	MALME-3M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCLT4H1	IGROV1	Investigative	[1]
Papillary renal cell carcinoma	DCQS69I	ACHN	Investigative	[1]
Plasma cell myeloma	DC0EZ50	RPMI-8226	Investigative	[1]
Pleural epithelioid mesothelioma	DC8VA2B	NCI-H226	Investigative	[1]
Renal cell carcinoma	DC4IIU3	SN12C	Investigative	[1]
Breast adenocarcinoma	DCBKMGH	MDA-MB-468	Investigative	[8]
Carcinoma	DCEOQSM	RXF 393	Investigative	[8]
Carcinoma	DCBG3DV	MCF7	Investigative	[8]
Invasive ductal carcinoma	DC7KOX2	T-47D	Investigative	[8]
Invasive ductal carcinoma	DC5L4VT	HS 578T	Investigative	[8]

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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [6] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [7] 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.
• [8] 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.