Details of the Drug Combination

General Information of Drug Combination (ID: DCUVHTP)

Drug Combination Name
CB-839 Everolimus
Indication
Disease Entry Status REF
Clear Cell Renal Cell Carcinoma Phase 2 [1]
Component Drugs CB-839   DM094UH Everolimus   DM8X2EH
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of CB-839
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [2]
Renal cell carcinoma 2C90 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
leukaemia 2A60-2B33 Phase 1 [3]
CB-839 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Glutaminase (GLS) TTCW0KX GLSK_HUMAN; GLSL_HUMAN Modulator [8]
------------------------------------------------------------------------------------
CB-839 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutaminase kidney isoform, mitochondrial (GLS) OTGOZG2M GLSK_HUMAN Decreases Activity [9]
------------------------------------------------------------------------------------
Indication(s) of Everolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [4]
Advanced/metastatic breast cancer 2C60 Approved [5]
Brainstem neoplasm N.A. Approved [4]
Breast carcinoma N.A. Approved [4]
Graft-versus-host disease 4B24 Approved [4]
Intracranial meningioma N.A. Approved [4]
Leukemia N.A. Approved [4]
Lung cancer 2C25.0 Approved [4]
Mucosal melanoma N.A. Approved [4]
Multiple sclerosis 8A40 Approved [4]
Plasma cell myeloma 2A83.1 Approved [4]
Prostate cancer 2C82.0 Approved [4]
Renal cell carcinoma 2C90 Approved [6]
Salivary gland squamous cell carcinoma N.A. Approved [4]
Tuberous sclerosis LD2D.2 Approved [4]
Kidney cancer 2C90.0 Phase 3 [6]
Castration-resistant prostate carcinoma N.A. Investigative [4]
Colon cancer 2B90.Z Investigative [4]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [7]
Neuroblastoma 2D11.2 Investigative [4]
Pancreatic acinar cell carcinoma N.A. Investigative [4]
Polycystic kidney disease GB8Y Investigative [4]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [7]
Everolimus Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [10]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [7]
------------------------------------------------------------------------------------
Everolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
------------------------------------------------------------------------------------
Everolimus Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
------------------------------------------------------------------------------------

References

1 ClinicalTrials.gov (NCT03163667) CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 ClinicalTrials.gov (NCT02071862) Study of the Glutaminase Inhibitor CB-839 in Solid Tumors. U.S. National Institutes of Health.
4 Everolimus FDA Label
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 5889).
7 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
8 Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014 Apr;13(4):890-901.
9 Dual inhibition of glutaminase and carnitine palmitoyltransferase decreases growth and migration of glutaminase inhibition-resistant triple-negative breast cancer cells. J Biol Chem. 2019 Jun 14;294(24):9342-9357.
10 Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
11 Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
12 The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.