Tenofovir alafenamide hemifumarate
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MedKoo CAT#: 319909

CAS#: 1392275-56-7 (hemifumarate)

Description: Tenofovir alafenamide hemifumarate, also known as Tenofovir alafenamide fumarate (2:1), is a nucleotide reverse transcriptase inhibitor (NRTIs) and a novel prodrug of tenofovir. By blocking reverse transcriptase, TAF prevent HIV from multiplying and can reduce the amount of HIV in the body. Tenofovir alafenamide is a prodrug, which means that it is an inactive drug. In the body, tenofovir alafenamide is converted to tenofovir diphosphate (TFV-DP). Tenofovir alafenamide fumarate was approved in November 2015 for treatment of HIV-1.


Chemical Structure

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Tenofovir alafenamide hemifumarate
CAS# 1392275-56-7 (hemifumarate)

Theoretical Analysis

MedKoo Cat#: 319909
Name: Tenofovir alafenamide hemifumarate
CAS#: 1392275-56-7 (hemifumarate)
Chemical Formula: C46H62N12O14P2
Exact Mass:
Molecular Weight: 1069.0195
Elemental Analysis: C, 51.68; H, 5.85; N, 15.72; O, 20.95; P, 5.79

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100.0mg USD 150.0 Ready to ship
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10.0g USD 2950.0 Ready to ship
20.0g USD 3850.0 Ready to ship
50.0g USD 4750.0 2 Weeks
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Related CAS #: 379270-38-9 (fumarate)   1392275-56-7 (hemifumarate)   379270-37-8 (free base)  

Synonym: TAF; GS734; GS-734; GS 734; GS 7340; GS-7340; GS7340; Tenofovir alafenamide hemifumarate; Tenofovir alafenamide fumarate (2:1); Genvoya.

IUPAC/Chemical Name: isopropyl ((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)-L-alaninate hemifumarate

InChi Key: SVUJNSGGPUCLQZ-FQQAACOVSA-N

InChi Code: InChI=1S/2C21H29N6O5P.C4H4O4/c2*1-14(2)31-21(28)16(4)26-33(29,32-17-8-6-5-7-9-17)13-30-15(3)10-27-12-25-18-19(22)23-11-24-20(18)27;5-3(6)1-2-4(7)8/h2*5-9,11-12,14-16H,10,13H2,1-4H3,(H,26,29)(H2,22,23,24);1-2H,(H,5,6)(H,7,8)/b;;2-1+/t2*15-,16+,33+;/m11./s1

SMILES Code: O=C(O)/C=C/C(O)=O.C[C@H](N[P@@](OC1=CC=CC=C1)(CO[C@H](C)CN2C=NC3=C(N)N=CN=C23)=O)C(OC(C)C)=O.C[C@H](N[P@@](OC4=CC=CC=C4)(CO[C@H](C)CN5C=NC6=C(N)N=CN=C56)=O)C(OC(C)C)=O

Appearance: White to off-white 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).

HS Tariff Code: 2934.99.9001

Biological target: Tenofovir alafenamide hemifumarate (GS-7340 hemifumarate) is an investigational oral prodrug of Tenofovir, which is a HIV-1 nucleotide reverse transcriptase inhibitor.
In vitro activity: TAF (tenofovir alafenamide hemifumarate ) reservoir implants were formed by compressing the TAF drug substance and small amounts of NaCl and magnesium stearate into a pellet that was impulse sealed into a 150- to 170-μm thin, medical-grade polyurethane tube (Fig. 1). Drug release from implants was evaluated in vitro (see Fig. S1 in the supplemental material) using the shake flask method. We observed low rates of TAF degradation (27) in phosphate-buffered saline (PBS) in in vitro release testing medium (halflife of 2.8 days at pH 7.4 at 37°C in PBS) as well as in the implant (see Supplemental 1 and 2 in the supplemental material file), although until the end of the release curve, we observed that >90% of the internal contents were in the parent form. The average TAF equivalent in vitro release rates over days 7 to 91 from the generation A implant were 0.13 mg/day for the 0.8-cm-long implants and 0.26 mg/day for the 1.6-cm-long implants, with fluxes of 0.24 mg TAF/cm2/day and 0.23 mg TAF/cm2/day, respectively. The mean TAF equivalent in vitro release rate over days 7 to 91 from the generation B implants was 0.13 mg/day, with an average flux of 0.08 mg TAF/cm2/day. In general, increases in the in vitro dose were correlated with increasing median TFV-DP concentrations. Reference: Antimicrob Agents Chemother. 2020 Mar; 64(3): e01893-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038301/
In vivo activity: The toxicity of tenofovir alafenamide (TAF) hemifumarate (HF) was evaluated when administered by continuous subcutaneous (s.c.) infusion via an external infusion pump for 28 days to rats and dogs. During the dosing period in dogs, in-life observations consisted of discharge at the infusion site with or without the presence of a skin lesion. Although infusion site reactions were observed in animals from all treatment groups, including vehicle controls, and were considered a consequence of the continuous s.c. infusion model, the frequency and severity of the reactions and associated observations were greater in TAF-treated animals, suggesting that infusion site reactions were exacerbated by administration of TAF HF. Administration of TAF HF to rats elicited changes in hematology parameters at a dose of ≥30 μg/kg/day. These changes included increases in white blood cell counts (WBC), neutrophil counts (NEUT), lymphocyte counts (LYMPH), monocyte counts (MONO), eosinophil counts (EOS), and platelet counts (PLT). Administration of TAF HF to rats was associated with minimal changes in clinical chemistry parameters at doses of ≥30 μg/kg/day. Alterations occurred in alkaline phosphatase activity (ALP), glucose (GLUC), total protein (TPROT), albumin (ALB), globulin (GLOB), albumin/globulin ratio (A/G ratio), and urea nitrogen (UREAN) concentrations. The main finding in this study is that TAF HF administered continuously as a s.c. infusion appears to exacerbate a background inflammation response to the presence of the s.c. catheter (foreign body response) in the tissue surrounding the infusion site in rats and dogs at all doses tested after 28 days of administration. Reference: Microbiol Spectr. 2021 Jun 30:e0033921. https://journals.asm.org/doi/10.1128/Spectrum.00339-21

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 75.0 70.16

Preparing Stock Solutions

The following data is based on the product molecular weight 1069.0195 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 2. Su JT, Simpson SM, Sung S, Tfaily EB, Veazey R, Marzinke M, Qiu J, Watrous D, Widanapathirana L, Pearson E, Peet MM, Karunakaran D, Grasperge B, Dobek G, Cain CM, Hope T, Kiser PF. A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01893-19. doi: 10.1128/AAC.01893-19. PMID: 31871073; PMCID: PMC7038301. 2. Zane D, Roller S, Shelton J, Singh R, Jain R, Wang Y, Yang B, Felx M, Alessi T, Feldman PL. A 28-Day Toxicity Study of Tenofovir Alafenamide Hemifumarate by Subcutaneous Infusion in Rats and Dogs. Microbiol Spectr. 2021 Jun 30:e0033921. doi: 10.1128/Spectrum.00339-21. Epub ahead of print. PMID: 34190595.
In vitro protocol: 1. Su JT, Simpson SM, Sung S, Tfaily EB, Veazey R, Marzinke M, Qiu J, Watrous D, Widanapathirana L, Pearson E, Peet MM, Karunakaran D, Grasperge B, Dobek G, Cain CM, Hope T, Kiser PF. A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01893-19. doi: 10.1128/AAC.01893-19. PMID: 31871073; PMCID: PMC7038301.
In vivo protocol: 2. Su JT, Simpson SM, Sung S, Tfaily EB, Veazey R, Marzinke M, Qiu J, Watrous D, Widanapathirana L, Pearson E, Peet MM, Karunakaran D, Grasperge B, Dobek G, Cain CM, Hope T, Kiser PF. A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01893-19. doi: 10.1128/AAC.01893-19. PMID: 31871073; PMCID: PMC7038301. 2. Zane D, Roller S, Shelton J, Singh R, Jain R, Wang Y, Yang B, Felx M, Alessi T, Feldman PL. A 28-Day Toxicity Study of Tenofovir Alafenamide Hemifumarate by Subcutaneous Infusion in Rats and Dogs. Microbiol Spectr. 2021 Jun 30:e0033921. doi: 10.1128/Spectrum.00339-21. Epub ahead of print. PMID: 34190595.

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1: Shafran SD, Di Perri G, Esser S, Lelièvre JD, Parczewski M. Planning HIV therapy to prevent future comorbidities: patient years for tenofovir alafenamide. HIV Med. 2019 Jun;20 Suppl 7:1-16. doi: 10.1111/hiv.12755. Review. PubMed PMID: 31099116.

2: Bictegravir/emtricitabine/tenofovir alafenamide for HIV infection. Aust Prescr. 2019 Apr;42(2):68-69. doi: 10.18773/austprescr.2019.016. Epub 2019 Feb 28. Review. PubMed PMID: 31048941; PubMed Central PMCID: PMC6478953.

3: Common Drug Review New Combination Product Submission: Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide (Symtuza): (Janssen Canada Inc.): Indication: A complete regimen for the treatment of HIV type 1 infection in adults and adolescents (aged 12 years and older with body weight at least 40 kg) with no known mutations associated with resistance to the individual components of Symtuza [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK540525/ PubMed PMID: 31034191.

4: CADTH Canadian Drug Expert Committee Recommendation: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (Symtuza — Janssen Inc.): Indication: Treatment of HIV type 1 (HIV-1) infection [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Jul. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK540287/ PubMed PMID: 31013021.

5: Clinical Review Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/FTC/TAF) (Biktarvy): (Gilead Sciences Canada, Inc.): Indication: A complete regimen for the treatment of HIV-1 infection in adults with no known substitution associated with resistance to the individual components of Biktarvy [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Oct. Available from http://www.ncbi.nlm.nih.gov/books/NBK539526/ PubMed PMID: 30958669.

6: Pharmacoeconomic Review Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/FTC/TAF) (Biktarvy): (Gilead Sciences Canada, Inc.): Indication: A complete regimen for the treatment of HIV-1 infection in adults with no known substitution associated with resistance the individual components of Biktarvy [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Oct. Available from http://www.ncbi.nlm.nih.gov/books/NBK539546/ PubMed PMID: 30958667.

7: CADTH Canadian Drug Expert Committee Recommendation: Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy — Gilead Sciences Canada, Inc.): Indication: As a complete regimen for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults with no known substitution associated with resistance to the individual components of Biktarvy [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Oct. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK539326/ PubMed PMID: 30942994.

8: Pharmacoeconomic Review Report: Emtricitabine/tenofovir alafenamide (Descovy) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK539225/ PubMed PMID: 30933443.

9: Clinical Review Report: Emtricitabine/tenofovir alafenamide fumarate (Descovy) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK538758/ PubMed PMID: 30883070.

10: CADTH Canadian Drug Expert Committee Final Recommendation: Emtricitabine/Tenofovir Alafenamide: (Descovy — Gilead Sciences Canada, Inc.): Indication: HIV-1 Infection [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Aug. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK538372/ PubMed PMID: 30860687.

11: Pham HT, Mesplède T. Bictegravir in a fixed-dose tablet with emtricitabine and tenofovir alafenamide for the treatment of HIV infection: pharmacology and clinical implications. Expert Opin Pharmacother. 2019 Mar;20(4):385-397. doi: 10.1080/14656566.2018.1560423. Epub 2019 Jan 30. Review. PubMed PMID: 30698467.

12: Giacomet V, Cossu MV, Capetti AF, Zuccotti G, Rizzardini G. An evaluation of elvitegravir plus cobicistat plus tenofovir alafenamide plus emtricitabine as a single-tablet regimen for the treatment of HIV in children and adolescents. Expert Opin Pharmacother. 2019 Feb;20(3):269-276. doi: 10.1080/14656566.2018.1559299. Epub 2018 Dec 26. Review. PubMed PMID: 30586314.

13: Clinical Review Report: Tenofovir Alafenamide (Vemlidy): (Gilead Sciences Canada, Inc.): Indication: Treatment of chronic hepatitis B in adults with compensated liver disease [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Apr. Available from http://www.ncbi.nlm.nih.gov/books/NBK533926/ PubMed PMID: 30475544.

14: Hill L, Smith SR, Karris MY. Profile of bictegravir/emtricitabine/tenofovir alafenamide fixed dose combination and its potential in the treatment of HIV-1 infection: evidence to date. HIV AIDS (Auckl). 2018 Oct 29;10:203-213. doi: 10.2147/HIV.S145529. eCollection 2018. Review. PubMed PMID: 30464641; PubMed Central PMCID: PMC6214311.

15: Squillace N, Bozzi G, Colella E, Gori A, Bandera A. Darunavir-cobicistat-emtricitabine-tenofovir alafenamide: safety and efficacy of a protease inhibitor in the modern era. Drug Des Devel Ther. 2018 Oct 29;12:3635-3643. doi: 10.2147/DDDT.S147493. eCollection 2018. Review. PubMed PMID: 30464395; PubMed Central PMCID: PMC6211373.

16: Deeks ED. Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. Review. Erratum in: Drugs. 2019 Mar 22;:. PubMed PMID: 30460547; PubMed Central PMCID: PMC6424950.

17: Pharmacoeconomic Review Report: Tenofovir Alafenamide (Vemlidy): (Gilead Sciences Canada, Inc.): Indication: Treatment of chronic hepatitis B in adults with compensated liver disease [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Apr. Available from http://www.ncbi.nlm.nih.gov/books/NBK532825/ PubMed PMID: 30427623.

18: CADTH Canadian Drug Expert Committee Recommendation: Tenofovir Alafenamide (Vemlidy - Gilead Sciences Canada, Inc.): Indication: Chronic Hepatitis B [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Mar 28. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK532703/ PubMed PMID: 30403460.

19: Childs-Kean LM, Egelund EF, Jourjy J. Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Monoinfection. Pharmacotherapy. 2018 Oct;38(10):1051-1057. doi: 10.1002/phar.2174. Epub 2018 Sep 9. Review. PubMed PMID: 30120841.

20: Byrne R, Carey I, Agarwal K. Tenofovir alafenamide in the treatment of chronic hepatitis B virus infection: rationale and clinical trial evidence. Therap Adv Gastroenterol. 2018 Jul 16;11:1756284818786108. doi: 10.1177/1756284818786108. eCollection 2018. Review. PubMed PMID: 30034532; PubMed Central PMCID: PMC6048601.



Additional Information

Related CAS#
CAS#379270-38-9 =Tenofovir alafenamide fumarate, 1:1
CAS#1392275-56-7= Tenofovir alafenamide hemifumarate, 2:1
CAS#379270-37-8 = Tenofovir alafenamide free base