Details of the Drug Combination

General Information of Drug Combination (ID: DCCE56W)

Drug Combination Name
10-hydroxycamptothecin SCH 727965
Indication
Disease Entry Status REF
Amelanotic melanoma Investigative [1]
Component Drugs 10-hydroxycamptothecin   DM9WLN4 SCH 727965   DMCJLD1
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MDA-MB-435
Zero Interaction Potency (ZIP) Score: 0.02
Bliss Independence Score: 3.24
Loewe Additivity Score: 2.01
LHighest Single Agent (HSA) Score: 2.02

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of 10-hydroxycamptothecin
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
10-hydroxycamptothecin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Inhibitor [2]
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10-hydroxycamptothecin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [4]
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10-hydroxycamptothecin Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Response To Substance [5]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Affects Response To Substance [6]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Response To Substance [5]
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Indication(s) of SCH 727965
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Discontinued in Phase 3 [3]
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]
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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]
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⏷ Show the Full List of 7 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Glioma DCXUHYR SF-295 Investigative [10]
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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 Upregulation of p21WAF1/CIP1 in human breast cancer cell lines MCF-7 and MDA-MB-468 undergoing apoptosis induced by natural product anticancer drugs 10-hydroxycamptothecin and camptothecin through p53-dependent and independent pathways. Int J Oncol. 1998 Apr;12(4):793-804.
3 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).
4 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
5 siRNA-mediated Bcl-2 and Bcl-xl gene silencing sensitizes human hepatoblastoma cells to chemotherapeutic drugs. Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):450-6. doi: 10.1111/j.1440-1681.2007.04593.x.
6 Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11636-41. doi: 10.1073/pnas.1934692100. Epub 2003 Sep 16.
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.