Details of the Drug Combination

General Information of Drug Combination (ID: DCV2D27)

Drug Combination Name
GDC-0084 Naltrexone
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs GDC-0084   DMA9SEY Naltrexone   DMUL45H
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HB3
Zero Interaction Potency (ZIP) Score: 5.509
Bliss Independence Score: 6.317
Loewe Additivity Score: 2.842
LHighest Single Agent (HSA) Score: 6.87

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of GDC-0084
Disease Entry ICD 11 Status REF
Glioblastoma of brain 2A00.00 Phase 2 [2]
GDC-0084 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Inhibitor [8]
------------------------------------------------------------------------------------
Indication(s) of Naltrexone
Disease Entry ICD 11 Status REF
Alcohol dependence 6C40.2 Approved [3]
Chronic alcoholism 6C40.2Z Approved [4]
Crohn disease DD70 Approved [5]
Gastroparesis DA41.00 Approved [5]
Inflammatory bowel disease DD72 Approved [5]
Obesity 5B81 Approved [5]
Ulcerative colitis DD71 Approved [5]
Human immunodeficiency virus infection 1C62 Phase 4 [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [7]
Chronic pain MG30 Investigative [5]
Naltrexone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor (OPR) TTN4QDT NOUNIPROTAC Antagonist [9]
------------------------------------------------------------------------------------
Naltrexone Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [10]
------------------------------------------------------------------------------------
Naltrexone Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Nitric oxide synthase, inducible (NOS2) OTKKIOJ1 NOS2_HUMAN Decreases Activity [11]
Follitropin subunit beta (FSHB) OTGLS283 FSHB_HUMAN Increases Expression [12]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [12]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Affects Response To Substance [9]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Increases Response [9]
Sodium-dependent dopamine transporter (SLC6A3) OT39XG28 SC6A3_HUMAN Affects Response To Substance [13]
Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2) OTAOZIGX GBRB2_HUMAN Affects Response To Substance [14]
D(2) dopamine receptor (DRD2) OTBLXKEG DRD2_HUMAN Affects Response To Substance [14]
Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6) OTX4UC3O GBRA6_HUMAN Affects Response To Substance [14]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
DD2 DC7SNNM DD2 Investigative [15]
------------------------------------------------------------------------------------

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 ClinicalTrials.gov (NCT03522298) Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma. U.S. National Institutes of Health.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 074918.
5 Naltrexone FDA Label
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: 1639).
7 ClinicalTrials.gov (NCT04365985) Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19. U.S. National Institutes of Health.
8 Current clinical development of PI3K pathway inhibitors in glioblastoma. Neuro Oncol. 2012 July; 14(7): 819-829.
9 An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44.
10 In vivo chronic exposure to heroin or naltrexone selectively inhibits liver microsome formation of estradiol-3-glucuronide in the rat. Biochem Pharmacol. 2008 Sep 1;76(5):672-9.
11 Low dose naltrexone therapy in multiple sclerosis. Med Hypotheses. 2005;64(4):721-4.
12 Chronic naltrexone treatment induces desensitization of the luteinizing hormone pulse generator for opioid blockade in hyperprolactinemic patients. J Clin Endocrinol Metab. 1995 May;80(5):1739-42. doi: 10.1210/jcem.80.5.7745028.
13 Association between the Stin2 VNTR polymorphism of the serotonin transporter gene and treatment outcome in alcohol-dependent patients. Alcohol Alcohol. 2008 Sep-Oct;43(5):516-22. doi: 10.1093/alcalc/agn048. Epub 2008 Jun 14.
14 Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009 Jul;14(3):328-37.
15 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.