"目錄號: HY-15232A

Anti-infection-

GS-7340(Tenofovir alafenamide)是抗病毒藥物替諾福韋（Tenofovir）的前體藥物腰懂，相比TFV disoproxil fumarate憔儿，GS-7340能更好的將TFV送達淋巴細(xì)胞和組織凛膏。

HIVReverse Transcriptase

相關(guān)產(chǎn)品

Dolutegravir-Maraviroc-Elvitegravir-Atazanavir sulfate-Tenofovir Disoproxil Fumarate-Tipranavir-Triciribine-Emtricitabine-Efavirenz-Miltefosine-Ritonavir-Delavirdine mesylate-Lamivudine-Abacavir-BI 224436-

生物活性

Description

GS-7340(Tenofovir alafenamide) is a prodrug of tenofovir (TFV) that more efficiently delivers TFV into lymphoid cells and tissues than TFV disoproxil fumarate.IC50 value:Target: NRTI; HIV reverse transcriptase inhibitorGS-7340 reduces first-pass clearance to be an effective oral prodrug, its permeability and stability were characterized in vitro and detailed pharmacokinetic studies were completed in dogs. GS-7340 showed concentration-dependent permeability through monolayers of caco-2 cells and dose-dependent oral bioavailability in dogs, increasing from 1.7% at 2 mg/kg to 24.7% at 20 mg/kg, suggesting saturable intestinal efflux transport [1]. Significant reductions in plasma HIV-1 RNA from baseline to day 11 were observed for all TAF dose groups compared with placebo (P < 0.01), with a median decrease of 1.08-1.73 log10 copies per milliliter, including a dose-response relationship for viral load decrease up to 25 mg [2].

Clinical Trial

NCT01671787

Gilead Sciences

Chronic Hepatitis B

March 2012

Phase 1

NCT02357602

University of North Carolina, Chapel Hill-Gilead Sciences

Healthy

March 2015

Phase 1

NCT02957994

Asian Pacific Liver Center at St. Vincent Medical Center

Hepatitis B

December 22, 2016

Phase 4

NCT00042289

National Institute of Allergy and Infectious Diseases (NIAID)-Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

HIV Infections

March 2003

Phase 4

NCT02957864

Erasmus Medical Center-Gilead Sciences

Renal Insufficiency,Chronic-Hiv-Therapeutic Agent Toxicity

October 2016

Phase 4

NCT02578550

Janssen Sciences Ireland UC

Healthy

November 2015

Phase 1

NCT00036634

Gilead Sciences

HIV Infections

March 2002

Phase 1-Phase 2

NCT02475135

Janssen Sciences Ireland UC

Healthy

June 2015

Phase 1

NCT02431247

Janssen Sciences Ireland UC

Immunodeficiency Virus Type 1, Human

July 6, 2015

Phase 3

NCT02556333

National Institute of Allergy and Infectious Diseases (NIAID)-National Institutes of Health Clinical Center (CC)

HIV-HBV

September 16, 2015

Phase 2

NCT02984852

Janssen Scientific Affairs, LLC

Healthy

December 2016

Phase 1

NCT03115736

University Hospital Inselspital, Berne

HIV and Hepatitis B Coinfection

May 23, 2017

Phase 2

NCT02962739

University of Colorado, Denver

Healthy Volunteers

March 2016

Phase 1

NCT03122262

Willem Daniel Francois Venter-University of Witwatersrand, South Africa

HIV-1 Infection

January 2017

Phase 3

NCT02859558

AIDS Clinical Trials Group-National Institute of Allergy and Infectious Diseases (NIAID)

HIV-1 Infection

January 2017

Phase 2

NCT02995252

University of Maryland

Hepatitis B， Chronic-Hepatitis C

December 2014

NCT02904369

CONRAD-United States Agency for International Development (USAID)-Agility Clinical, Inc.

HIV

October 2016

Phase 1

NCT03048422

National Institute of Allergy and Infectious Diseases (NIAID)

HIV Infections

July 2017

Phase 3

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References

[1].Babusis D, et al. Mechanism for effective lymphoid cell and tissue loading following oral administration of nucleotide prodrug GS-7340. Mol Pharm. 2013 Feb 4;10(2):459-66.

[2].Ruane PJ, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):449-55.