Cobicistat

Cobicistat
Clinical data
Pronunciation/koʊˈbɪsɪstæt/
koh-BIS-i-stat
Trade namesTybost
Other namesGS-9350
AHFS/Drugs.comMonograph
MedlinePlusa616029
License data
ATC code
Legal status
Legal status
Identifiers
  • 1,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)-2-[(methyl{[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4-yl)butanoyl]amino}-1,6-diphenylhexan-2-yl]carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC40H53N7O5S2
Molar mass776.03 g·mol−1
3D model (JSmol)
  • CC(C)c1nc(cs1)CN(C)C(=O)NC(CCN2CCOCC2)C(=O)NC(CCC(Cc3ccccc3)NC(=O)OCc4cncs4)Cc5ccccc5
  • InChI=1S/C40H53N7O5S2/c1-29(2)38-43-34(27-53-38)25-46(3)39(49)45-36(16-17-47-18-20-51-21-19-47)37(48)42-32(22-30-10-6-4-7-11-30)14-15-33(23-31-12-8-5-9-13-31)44-40(50)52-26-35-24-41-28-54-35/h4-13,24,27-29,32-33,36H,14-23,25-26H2,1-3H3,(H,42,48)(H,44,50)(H,45,49)/t32-,33-,36+/m1/s1 checkY
  • Key:ZCIGNRJZKPOIKD-CQXVEOKZSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Cobicistat, sold under the brand name Tybost, is a medication for use in the treatment of human immunodeficiency virus infection (HIV/AIDS). Its major mechanism of action is through the inhibition of human CYP3A proteins.[1][non-primary source needed]

Like ritonavir (Norvir), cobicistat is of interest for its ability to inhibit liver enzymes that metabolize other medications used to treat HIV, notably elvitegravir, an HIV integrase inhibitor. By combining cobicistat with elvitegravir, higher concentrations of the latter are achieved in the body with lower dosing, theoretically enhancing elvitegravir's viral suppression while diminishing its adverse side-effects. In contrast with ritonavir, the only other booster approved for use as a part of HAART, cobicistat has no anti-HIV activity of its own.[2]

Cobicistat is a component of three four-drug, fixed-dose combination HIV treatments. The first, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil, is marketed as Stribild and was approved by the FDA in August 2012 for use in the United States.[2][3] The second, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, is marketed as Genvoya and was approved by the FDA in November 2015 for use in the United States. Both Stribild and Genvoya are owned by Gilead Sciences. The third, cobicistat/darunavir/emtricitabine/tenofovir alafenamide, is marketed as Symtuza and was FDA approved July 17, 2018 and is owned by Janssen Pharmaceuticals.[4]

Additionally, there is a fixed-dose combination of cobicistat and the protease inhibitor darunavir (darunavir/cobicistat; marketed as Prezcobix by Janssen Therapeutics), and a fixed-dose combination of cobicistat and protease inhibitor atazanavir (atazanavir/cobicistat; marketed as Evotaz by Bristol-Myers Squibb). Both Prezcobix and Evotaz were approved by the FDA in January 2015.

Cobicistat is a potent inhibitor of cytochrome P450 3A enzymes, including the important CYP3A4 subtype. It also inhibits intestinal transport proteins, increasing the overall absorption of several HIV medications, including atazanavir, darunavir, and tenofovir alafenamide.[5]

  1. ^ Mathias AA, German P, Murray BP, Wei L, Jain A, West S, et al. (March 2010). "Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity". Clinical Pharmacology and Therapeutics. 87 (3): 322–9. doi:10.1038/clpt.2009.228. PMID 20043009. S2CID 29197109.
  2. ^ a b Highleyman, L. Elvitegravir "Quad" Single-tablet Regimen Shows Continued HIV Suppression at 48 Weeks Archived 3 March 2016 at the Wayback Machine. HIV and Hepatitis.com
  3. ^ R Elion, J Gathe, B Rashbaum, and others. The Single-Tablet Regimen of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (EVG/COBI/FTC/TDF; Quad) Maintains a High Rate of Virologic Suppression, and Cobicistat (COBI) is an Effective Pharmacoenhancer Through 48 Weeks. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12–15, 2010.
  4. ^ "Symtuza (cobicistat, darunavir, emtricitabine and tenofovir alafenamide) FDA Approval History". Drugs.com. Retrieved 30 October 2019.
  5. ^ Lepist EI, Phan TK, Roy A, Tong L, Maclennan K, Murray B, Ray AS (October 2012). "Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro". Antimicrobial Agents and Chemotherapy. 56 (10): 5409–13. doi:10.1128/AAC.01089-12. PMC 3457391. PMID 22850510.