Fosdevirine

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 319724

CAS#: 1018450-26-4

Description: Fosdevirine, also known as GSK2248761 and IDX899, a Highly Potent Anti-HIV Non-nucleoside Reverse Transcriptase Inhibitor having an EC50 of 11 nM against the Y181C/K103N double mutant. GSK2248761 is a novel, once-daily (QD), next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains. GSK2248761 at 100 to 800 mg QD for 7 days was well tolerated, demonstrated potent antiviral activity in treatment-naive HIV-infected subjects, and had favorable PK and resistance profiles. GSK2248761 is no longer in clinical development.


Price and Availability

Size
Price

Size
Price

Size
Price

Fosdevirine is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

img

Theoretical Analysis

MedKoo Cat#: 319724
Name: Fosdevirine
CAS#: 1018450-26-4
Chemical Formula: C20H17ClN3O3P
Exact Mass: 413.0696
Molecular Weight: 413.7978
Elemental Analysis: C, 58.05; H, 4.14; Cl, 8.57; N, 10.15; O, 11.60; P, 7.49


Synonym: GSK2248761; GSK-2248761; GSK 2248761; GSK2248761A; GSK-2248761A; GSK 2248761A; IDX899; IDX-899; IDX 899, Fosdevirine.

IUPAC/Chemical Name: methyl (E)-(2-carbamoyl-5-chloro-1H-indol-3-yl)(3-(2-cyanovinyl)-5-methylphenyl)phosphinate

InChi Key: CGBYTKOSZYQOPV-ONEGZZNKSA-N

InChi Code: InChI=1S/C20H17ClN3O3P/c1-12-8-13(4-3-7-22)10-15(9-12)28(26,27-2)19-16-11-14(21)5-6-17(16)24-18(19)20(23)25/h3-6,8-11,24H,1-2H3,(H2,23,25)/b4-3+

SMILES Code: O=P(C1=CC(C)=CC(/C=C/C#N)=C1)(C2=C(C(N)=O)NC3=C2C=C(Cl)C=C3)OC


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Dousson C, Alexandre FR, Amador A, Bonaric S, Bot S, Caillet C, Convard T, da Costa D, Lioure MP, Roland A, Rosinovsky E, Maldonado S, Parsy C, Trochet C, Storer R, Stewart A, Wang J, Mayes BA, Musiu C, Poddesu B, Vargiu L, Liuzzi M, Moussa A, Jakubik J, Hubbard L, Seifer M, Standring D. Discovery of the Aryl-phospho-indole IDX899, a Highly Potent Anti-HIV Non-nucleoside Reverse Transcriptase Inhibitor. J Med Chem. 2016 Feb 3. [Epub ahead of print] PubMed PMID: 26804933.

2: Margolis DA, Eron JJ, DeJesus E, White S, Wannamaker P, Stancil B, Johnson M. Unexpected finding of delayed-onset seizures in HIV-positive, treatment-experienced subjects in the Phase IIb evaluation of fosdevirine (GSK2248761). Antivir Ther. 2014;19(1):69-78. doi: 10.3851/IMP2689. Epub 2013 Oct 24. PubMed PMID: 24158593.

3: Ölgen S. Recent development of new substituted indole and azaindole derivatives as anti-HIV agents. Mini Rev Med Chem. 2013 Oct;13(12):1700-8. Review. PubMed PMID: 23895189.

4: Castellino S, Groseclose MR, Sigafoos J, Wagner D, de Serres M, Polli JW, Romach E, Myer J, Hamilton B. Central nervous system disposition and metabolism of Fosdevirine (GSK2248761), a non-nucleoside reverse transcriptase inhibitor: an LC-MS and Matrix-assisted laser desorption/ionization imaging MS investigation into central nervous system toxicity. Chem Res Toxicol. 2013 Feb 18;26(2):241-51. doi: 10.1021/tx3004196. Epub 2012 Dec 20. PubMed PMID: 23227887.

5: Zala C, St Clair M, Dudas K, Kim J, Lou Y, White S, Piscitelli S, Dumont E, Pietropaolo K, Zhou XJ, Mayers D. Safety and efficacy of GSK2248761, a next-generation nonnucleoside reverse transcriptase inhibitor, in treatment-naive HIV-1-infected subjects. Antimicrob Agents Chemother. 2012 May;56(5):2570-5. doi: 10.1128/AAC.05597-11. Epub 2012 Feb 6. PubMed PMID: 22314532; PubMed Central PMCID: PMC3346662.

6: Piscitelli S, Kim J, Gould E, Lou Y, White S, de Serres M, Johnson M, Zhou XJ, Pietropaolo K, Mayers D. Drug interaction profile for GSK2248761, a next generation non-nucleoside reverse transcriptase inhibitor. Br J Clin Pharmacol. 2012 Aug;74(2):336-45. doi: 10.1111/j.1365-2125.2012.04194.x. PubMed PMID: 22288567; PubMed Central PMCID: PMC3630753.

7: La Regina G, Coluccia A, Silvestri R. Looking for an active conformation of the future HIV type-1 non-nucleoside reverse transcriptase inhibitors. Antivir Chem Chemother. 2010 Aug 11;20(6):213-37. doi: 10.3851/IMP1607. Review. PubMed PMID: 20710063.

8: Klibanov OM, Kaczor RL. IDX-899, an aryl phosphinate-indole non-nucleoside reverse transcriptase inhibitor for the potential treatment of HIV infection. Curr Opin Investig Drugs. 2010 Feb;11(2):237-45. Review. PubMed PMID: 20112173.

9: Zhou XJ, Garner RC, Nicholson S, Kissling CJ, Mayers D. Microdose pharmacokinetics of IDX899 and IDX989, candidate HIV-1 non-nucleoside reverse transcriptase inhibitors, following oral and intravenous administration in healthy male subjects. J Clin Pharmacol. 2009 Dec;49(12):1408-16. doi: 10.1177/0091270009343698. Epub 2009 Sep 23. PubMed PMID: 19776293.

10: Zhou XJ, Pietropaolo K, Damphousse D, Belanger B, Chen J, Sullivan-Bólyai J, Mayers D. Single-dose escalation and multiple-dose safety, tolerability, and pharmacokinetics of IDX899, a candidate human immunodeficiency virus type 1 nonnucleoside reverse transcriptase inhibitor, in healthy subjects. Antimicrob Agents Chemother. 2009 May;53(5):1739-46. doi: 10.1128/AAC.01479-08. Epub 2009 Feb 17. PubMed PMID: 19223643; PubMed Central PMCID: PMC2681571.

11: Mascolini M, Larder BA, Boucher CA, Richman DD, Mellors JW. Broad advances in understanding HIV resistance to antiretrovirals: report on the XVII International HIV Drug Resistance Workshop. Antivir Ther. 2008;13(8):1097-113. PubMed PMID: 19195337.

12: Dalton P. Two new NNRTIs enter the pipeline. Proj Inf Perspect. 2008 Sep;(46):13. PubMed PMID: 19048672.

13: Sweeney ZK, Klumpp K. Improving non-nucleoside reverse transcriptase inhibitors for first-line treatment of HIV infection: the development pipeline and recent clinical data. Curr Opin Drug Discov Devel. 2008 Jul;11(4):458-70. Review. PubMed PMID: 18600563.