Details of the Drug Combination

General Information of Drug Combination (ID: DCOZWBI)

• Drug Combination Name: Taxol + MK-4827
• Indication: Malignant melanoma; Status: Investigative [1]
• Component Drugs:
  Taxol (DMUOT9V): Small molecular drug
  MK-4827 (DMLYGH4): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HT144
  Zero Interaction Potency (ZIP) Score: 4.46
  Bliss Independence Score: 3.84
  Loewe Additivity Score: 6.71
  LHighest Single Agent (HSA) Score: 8.61

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Taxol

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Pancreatic cancer	2C10	Phase 3	[4]
Gastric adenocarcinoma	2B72	Phase 2	[5]
Ovarian cancer	2C73	Phase 2	[5]

Taxol Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Apoptosis regulator Bcl-2 (BCL-2)	TTJGNVC	BCL2_HUMAN	Modulator	[2]
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[2]

Indication(s) of MK-4827

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 3	[6]
Breast cancer	2C60-2C65	Phase 2	[4]
Ewing sarcoma	2B52	Phase 1	[4]

MK-4827 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Poly [ADP-ribose] polymerase (PARP)	TTEBCY8	NOUNIPROTAC	Modulator	[7]

MK-4827 Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[8]
Carboxylesterase 1 (CES1)	DEB30C5	EST1_HUMAN	Metabolism	[9]
Beta-glucuronidase (GUSB)	DEP54UE	BGLR_HUMAN	Metabolism	[9]

MK-4827 Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DCZKYOP	ES2	Investigative	[11]
Breast and ovarian cancer syndrome	DCWCOXW	UWB1289	Investigative	[12]
Breast and ovarian cancer syndrome	DC87280	UWB1289+BRCA1	Investigative	[12]
Breast carcinoma	DCLGQ69	KPL1	Investigative	[12]
Breast carcinoma	DCDQW9D	OCUBM	Investigative	[12]
Carcinoma	DCI4NAJ	OV90	Investigative	[12]
Carcinoma	DC7OV6C	EFM192B	Investigative	[12]
Colon adenocarcinoma	DCDF9YY	LOVO	Investigative	[12]
Colon carcinoma	DCXTNRG	RKO	Investigative	[12]
Invasive ductal carcinoma	DCYMBDC	T-47D	Investigative	[12]
Rectal adenocarcinoma	DCKBMZY	SW837	Investigative	[12]
Adenocarcinoma	DC59LE0	NCIH1650	Investigative	[1]
Adenocarcinoma	DCXKUGN	NCIH520	Investigative	[1]
Adenocarcinoma	DCMOP06	COLO320DM	Investigative	[1]
Adenocarcinoma	DCCZUCO	DLD1	Investigative	[1]
Adenocarcinoma	DCZ8K39	HT29	Investigative	[1]
Adenocarcinoma	DCWATTV	SW-620	Investigative	[1]
Large cell lung carcinoma	DCFVW72	NCI-H460	Investigative	[1]
Malignant melanoma	DCDMG9B	RPMI7951	Investigative	[1]
Malignant melanoma	DCJW27T	SKMEL30	Investigative	[1]
Mesothelioma	DCX9FK0	MSTO	Investigative	[1]
Non small cell carcinoma	DCATH9F	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DC1PCTG	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCT41RY	SK-OV-3	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] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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] ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
• [7] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [8] Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
• [9] Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
• [10] Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
• [11] 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.
• [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.