Details of the Drug Combination

General Information of Drug Combination (ID: DCVRVAO)

• Drug Combination Name: SCH 727965 + RTB101
• Indication: Ewing sarcoma-peripheral primitive neuroectodermal tumour; Status: Investigative [1]
• Component Drugs:
  SCH 727965 (DMCJLD1): Small molecular drug
  RTB101 (DM62QTW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: ES2
  Zero Interaction Potency (ZIP) Score: 6.87
  Bliss Independence Score: 4.9
  Loewe Additivity Score: 2.41
  LHighest Single Agent (HSA) Score: 9.71

Molecular Interaction Atlas of This Drug Combination

Indication(s) of SCH 727965

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

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	[5]
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[5]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[5]

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	[6]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[6]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Decreases Expression	[7]
Breast cancer type 2 susceptibility protein (BRCA2)	OTF1XSV1	BRCA2_HUMAN	Decreases Expression	[7]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[7]
Fanconi anemia group D2 protein (FANCD2)	OTVEB5LF	FACD2_HUMAN	Decreases Expression	[7]
Cyclin-dependent kinase 12 (CDK12)	OTZUDGNU	CDK12_HUMAN	Decreases Activity	[7]

Indication(s) of RTB101

Disease Entry	ICD 11	Status	REF
Respiratory tract infection	CA45	Phase 3	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]

RTB101 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
CREB-regulated transcription coactivator 1 (TORC1)	TT4GO0F	CRTC1_HUMAN	Inhibitor	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DC6OAUB	UWB1289	Investigative	[9]
Breast and ovarian cancer syndrome	DC9YP2G	UWB1289+BRCA1	Investigative	[9]
Breast carcinoma	DC932MB	KPL1	Investigative	[9]
Breast carcinoma	DCE2309	OCUBM	Investigative	[9]
Carcinoma	DCZPD8J	EFM192B	Investigative	[9]
Carcinoma	DCUI5MH	MDAMB436	Investigative	[9]
Colon adenocarcinoma	DC1G1GT	LOVO	Investigative	[9]
Colon carcinoma	DCFWUUJ	RKO	Investigative	[9]
Rectal adenocarcinoma	DCIYXJ2	SW837	Investigative	[9]
Adenocarcinoma	DCZPUJP	CAOV3	Investigative	[10]
Adenocarcinoma	DCG8JG3	A427	Investigative	[10]
Adenocarcinoma	DCQGR5Z	NCIH1650	Investigative	[10]
Adenocarcinoma	DCKTMAI	NCIH23	Investigative	[10]
Adenocarcinoma	DCKTV40	NCIH520	Investigative	[10]
Adenocarcinoma	DCO4K1X	COLO320DM	Investigative	[10]
Adenocarcinoma	DCN0FCN	DLD1	Investigative	[10]
Adenocarcinoma	DCTTJO9	HCT116	Investigative	[10]
Adenocarcinoma	DCFPIIA	HT29	Investigative	[10]
Adenocarcinoma	DCEGMN5	SW-620	Investigative	[10]
Amelanotic melanoma	DCWCVOI	A2058	Investigative	[10]
Germ cell tumour	DCHBUCT	PA1	Investigative	[10]
Large cell lung carcinoma	DCI057A	NCI-H460	Investigative	[10]
Malignant melanoma	DC38Q9O	A375	Investigative	[10]
Malignant melanoma	DCZ590L	HT144	Investigative	[10]
Malignant melanoma	DCLY1M6	RPMI7951	Investigative	[10]
Malignant melanoma	DCBBX9G	SKMEL30	Investigative	[10]
Malignant melanoma	DCHBIG2	UACC62	Investigative	[10]
Mesothelioma	DCDAWN4	MSTO	Investigative	[10]
Non small cell carcinoma	DCB2QR9	SKMES1	Investigative	[10]
Ovarian endometrioid adenocarcinoma	DCYZG6H	A2780	Investigative	[10]
Ovarian serous cystadenocarcinoma	DCNHMMU	SK-OV-3	Investigative	[10]
Prostate carcinoma	DCH3S9D	LNCAP	Investigative	[10]
Prostate carcinoma	DCRSEZH	VCAP	Investigative	[10]

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: 7379).
• [3] ClinicalTrials.gov (NCT04139915) Effect of RTB101 on Illness Associated With Respiratory Tract Infections in the Elderly. U.S. National Institutes of Health.
• [4] ClinicalTrials.gov (NCT04409327) Phase 2 Study to Determine if RTB101 Reduces the Severity of COVID-19 in Older Adults Residing in Nursing Homes. U.S. National Institutes of Health.
• [5] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [6] 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.
• [7] 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.
• [8] Anti-ageing pipeline starts to mature.Nat Rev Drug Discov. 2018 Sep;17(9):609-612.
• [9] 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.
• [10] 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.