Details of the Drug Combination

General Information of Drug Combination (ID: DCP28LT)

Drug Combination Name
Carboplatin UCN-01
Indication
Disease Entry Status REF
Unspecified Adult Solid Tumor, Protocol Specific Phase 1 [1]
Component Drugs Carboplatin   DMG281S UCN-01   DMUNJZB
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Carboplatin
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [2]
Carcinoma 2A00-2F9Z Approved [2]
Cholangiocarcinoma 2C12.10 Approved [2]
Cutaneous melanoma 2C30 Approved [2]
Epithelial ovarian cancer 2B5D Approved [2]
Fallopian tube neoplasm N.A. Approved [2]
Gastroesophageal junction adenocarcinoma 2B71 Approved [2]
Lung adenocarcinoma N.A. Approved [2]
Lung cancer 2C25.0 Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [2]
Ovarian cancer 2C73 Approved [3]
Ovarian disorder N.A. Approved [2]
Ovarian neoplasm N.A. Approved [2]
Ovarian serous cystadenocarcinoma N.A. Approved [2]
Small-cell lung cancer 2C25.Y Approved [2]
Lung large cell carcinoma N.A. Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
Carboplatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [5]
------------------------------------------------------------------------------------
Carboplatin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
High affinity copper uptake protein 1 (SLC31A1) DTP8L4F COPT1_HUMAN Substrate [6]
------------------------------------------------------------------------------------
Carboplatin Interacts with 7 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [7]
Glutathione S-transferase theta-1 (GSTT1) DE3PKUG GSTT1_HUMAN Metabolism [7]
Metallothionein-1A (MT1A) DE5ME8A MT1A_HUMAN Metabolism [7]
Metallothionein-2A (MT2A) DEFKGT7 MT2_HUMAN Metabolism [7]
Myeloperoxidase (MPO) DEA3U9Y PERM_HUMAN Metabolism [7]
Quinone reductase 1 (NQO1) DENP5RY NQO1_HUMAN Metabolism [7]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Metabolism [7]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 DME(s)
Indication(s) of UCN-01
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Phase 2 [4]
UCN-01 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Inhibitor [9]
------------------------------------------------------------------------------------
UCN-01 Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
------------------------------------------------------------------------------------
UCN-01 Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
3-phosphoinositide-dependent protein kinase 1 (PDPK1) OTT09ZVP PDPK1_HUMAN Decreases Activity [11]
Tyrosine-protein kinase Lck (LCK) OT883FG9 LCK_HUMAN Decreases Activity [11]
Protein kinase C alpha type (PRKCA) OT5UWNRD KPCA_HUMAN Decreases Activity [11]
Ribosomal protein S6 kinase alpha-3 (RPS6KA3) OTYJNNMD KS6A3_HUMAN Decreases Activity [11]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Decreases Activity [12]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Decreases Expression [13]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Increases Expression [14]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Increases Expression [14]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [8]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [8]
BAG family molecular chaperone regulator 1 (BAG1) OTRQNIA4 BAG1_HUMAN Decreases Expression [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Response To Substance [15]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Response To Substance [16]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 DOT(s)

References

1 ClinicalTrials.gov (NCT00036777) UCN-01 and Carboplatin in Treating Patients With Advanced Solid Tumors
2 Carboplatin FDA Label
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: 7624).
4 ClinicalTrials.gov (NCT00082017) UCN-01 (7-Hydroxystaurosporine) to Treat Relapsed T-Cell Lymphomas. U.S. National Institutes of Health.
5 Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
6 Overcoming platinum drug resistance with copper-lowering agents. Anticancer Res. 2013 Oct;33(10):4157-61.
7 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
8 Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate antiapoptosis proteins in B-cell chronic lymphocytic leukemia. Blood. 2000 Jul 15;96(2):393-7.
9 Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening app... J Mol Graph Model. 2009 Sep;28(2):113-30.
10 Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
11 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
12 Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity. Toxicol Sci. 2013 Oct;135(2):402-13. doi: 10.1093/toxsci/kft167. Epub 2013 Jul 28.
13 UCN-01 induces cytotoxicity toward human CLL cells through a p53-independent mechanism. Exp Hematol. 2001 Jun;29(6):703-8. doi: 10.1016/s0301-472x(01)00649-x.
14 The expression of retinoblastoma and Sp1 is increased by low concentrations of cyclin-dependent kinase inhibitors. Eur J Biochem. 2003 Dec;270(24):4809-22. doi: 10.1046/j.1432-1033.2003.03874.x.
15 The PARP inhibitor PJ34 causes a PARP1-independent, p21 dependent mitotic arrest. DNA Repair (Amst). 2011 Oct 10;10(10):1003-13. doi: 10.1016/j.dnarep.2011.07.006. Epub 2011 Aug 12.
16 A study of cytotoxic synergy of UCN-01 and flavopiridol in syngeneic pair of cell lines. Invest New Drugs. 2005 Aug;23(4):299-309. doi: 10.1007/s10637-005-1438-y.