General Information of Drug Combination (ID: DCZZCCT)

Drug Combination Name
Gemfibrozil CC-292
Indication
Disease Entry Status REF
Multiple Sclerosis Phase 1 [1]
Component Drugs Gemfibrozil   DMD8Q3J CC-292   DMJR9H0
Small molecular drug 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 Gemfibrozil
Disease Entry ICD 11 Status REF
Hyperlipidaemia 5C80 Approved [2]
Gemfibrozil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Lipoprotein lipase (LPL) TTOF3WZ LIPL_HUMAN Activator [5]
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Gemfibrozil Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [7]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [7]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [8]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [7]
Catechol-2,3-dioxygenase (caD) DEFKSVZ A0A371SLU3_9BACI Metabolism [9]
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⏷ Show the Full List of 6 DME(s)
Gemfibrozil Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [4]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Increases Expression [4]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Decreases Activity [10]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [11]
Bifunctional epoxide hydrolase 2 (EPHX2) OTPTRCNW HYES_HUMAN Affects Expression [12]
Cytochrome P450 2J2 (CYP2J2) OTJBTEH8 CP2J2_HUMAN Affects Expression [12]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Increases Expression [13]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Increases Expression [14]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [15]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Decreases Expression [15]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Decreases Expression [16]
Cytochrome P450 7A1 (CYP7A1) OT8Z5KLD CP7A1_HUMAN Decreases Expression [17]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Increases Expression [14]
Oxysterols receptor LXR-beta (NR1H2) OT4APA60 NR1H2_HUMAN Increases Expression [14]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Increases Expression [14]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Increases Expression [14]
Oxysterols receptor LXR-alpha (NR1H3) OT54YZ9I NR1H3_HUMAN Increases Expression [14]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Increases Expression [13]
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⏷ Show the Full List of 18 DOT(s)
Indication(s) of CC-292
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Phase 2 [3]
CC-292 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase BTK (ATK) TTGM6VW BTK_HUMAN Modulator [3]
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References

1 ClinicalTrials.gov (NCT06064539) Study of Drug-drug Interaction of the Effects of Gemfibrozil and Rifampicin on SAR442168 in Healthy Adult Subjects
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: 3439).
3 Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans. J Pharmacol Exp Ther. 2013 Aug;346(2):219-28.
4 Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes. Pharm Res. 2005 Jan;22(1):71-8.
5 Mode of action of fibrates in the regulation of triglyceride and HDL-cholesterol metabolism. Drugs Today (Barc). 2006 Jan;42(1):39-64.
6 Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998 Feb;34(2):155-62.
7 The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4.
8 Comprehensive pharmacogenomic study reveals an important role of UGT1A3 in montelukast pharmacokinetics. Clin Pharmacol Ther. 2018 Jul;104(1):158-168.
9 Genomic, proteomic, and metabolite characterization of gemfibrozil-degrading organism Bacillus sp. GeD10. Environ Sci Technol. 2016 Jan 19;50(2):744-55.
10 Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers. Eur J Pharmacol. 2008 Apr 28;584(2-3):213-21.
11 Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class. Toxicol Lett. 2016 Jan 22;241:82-94.
12 Expression of cytochrome P450 epoxygenases and soluble epoxide hydrolase is regulated by hypolipidemic drugs in dose-dependent manner. Toxicol Appl Pharmacol. 2018 Sep 15;355:156-163.
13 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
14 On the mechanism for PPAR agonists to enhance ABCA1 gene expression. Atherosclerosis. 2009 Aug;205(2):413-9. doi: 10.1016/j.atherosclerosis.2009.01.008. Epub 2009 Jan 19.
15 Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol. Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1783-9. doi: 10.1161/hq1001.096624.
16 Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. Arterioscler Thromb Vasc Biol. 1999 Jun;19(6):1577-81. doi: 10.1161/01.atv.19.6.1577.
17 Fibrates modify the expression of key factors involved in bile-acid synthesis and biliary-lipid secretion in gallstone patients. Eur J Clin Pharmacol. 2004 Feb;59(12):855-61. doi: 10.1007/s00228-003-0704-1. Epub 2003 Dec 18.