Details of the Drug Combination

General Information of Drug Combination (ID: DC3W6XM)

• Drug Combination Name: Taxol + SCH 727965
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Taxol (DMUOT9V): Small molecular drug
  SCH 727965 (DMCJLD1): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HT29
  Zero Interaction Potency (ZIP) Score: 5.71
  Bliss Independence Score: 4.26
  Loewe Additivity Score: 2.6
  LHighest Single Agent (HSA) Score: 9.11

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 SCH 727965

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Discontinued in Phase 3	[6]

SCH 727965 Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 9 (CDK9)	TT1LVF2	CDK9_HUMAN	Inhibitor	[7]
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[7]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[7]

SCH 727965 Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[8]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[8]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Decreases Expression	[9]
Breast cancer type 2 susceptibility protein (BRCA2)	OTF1XSV1	BRCA2_HUMAN	Decreases Expression	[9]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[9]
Fanconi anemia group D2 protein (FANCD2)	OTVEB5LF	FACD2_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase 12 (CDK12)	OTZUDGNU	CDK12_HUMAN	Decreases Activity	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Anaplastic large cell lymphoma	DC8CYQJ	SR	Investigative	[10]
Childhood T acute lymphoblastic leukemia	DCZSJPL	CCRF-CEM	Investigative	[10]
Chronic myelogenous leukemia	DCDGE1S	K-562	Investigative	[10]
Clear cell renal cell carcinoma	DC4ICDI	786-0	Investigative	[10]
Clear cell renal cell carcinoma	DCJQ765	CAKI-1	Investigative	[10]
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DC5WLVV	ES2	Investigative	[10]
Glioblastoma	DCRLJPR	SNB-75	Investigative	[10]
Glioma	DCD02A3	SF-295	Investigative	[10]
Glioma	DCYKUK5	SF-539	Investigative	[10]
Papillary renal cell carcinoma	DCKU2O8	ACHN	Investigative	[10]
Plasma cell myeloma	DC3X79A	RPMI-8226	Investigative	[10]
Colon carcinoma	DCX9VG3	KM12	Investigative	[11]
Invasive ductal carcinoma	DCBVHW3	HS 578T	Investigative	[11]
Rectal adenocarcinoma	DCTF34Y	SW837	Investigative	[11]
Adenocarcinoma	DCRX4P6	CAOV3	Investigative	[1]
Adenocarcinoma	DC179M2	A427	Investigative	[1]
Adenocarcinoma	DC7V25M	NCIH520	Investigative	[1]
Adenocarcinoma	DC0QVLQ	NCIH23	Investigative	[1]
Adenocarcinoma	DCYJW5I	COLO320DM	Investigative	[1]
Adenocarcinoma	DCYJXV5	HCT116	Investigative	[1]
Adenocarcinoma	DC896L4	SW-620	Investigative	[1]
Amelanotic melanoma	DCS1NLX	A2058	Investigative	[1]
Amelanotic melanoma	DC96IE4	M14	Investigative	[1]
Cutaneous melanoma	DCIIFVL	SK-MEL-5	Investigative	[1]
Germ cell tumour	DCY64R5	PA1	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC5M15X	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCO0H3K	NCI\\/ADR-RES	Investigative	[1]
Malignant melanoma	DCOOBWK	A375	Investigative	[1]
Malignant melanoma	DCOC51Q	UACC62	Investigative	[1]
Malignant melanoma	DCPXMIP	LOX IMVI	Investigative	[1]
Mesothelioma	DC4IGH4	MSTO	Investigative	[1]
Minimally invasive lung adenocarcinoma	DC7G4M2	NCI-H322M	Investigative	[1]
Non small cell carcinoma	DCELY2Y	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCVKKNJ	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCXD9BX	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] 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: 7379).
• [7] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [8] Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53. doi: 10.1158/1535-7163.MCT-10-0324. Epub 2010 Jul 27.
• [9] CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer. Cell Rep. 2016 Nov 22;17(9):2367-2381. doi: 10.1016/j.celrep.2016.10.077.
• [10] 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.
• [11] 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.