Investigational Drug Details
| Drug ID: | D358 |
| Drug Name: | TAF |
| Synonyms: | Tenofovir alafenamide |
| Type: | Chemical drug |
| DrugBank ID: | DB09299 |
| DrugBank Description: | Tenofovir alafenamide is a novel prodrug developed in order to improve renal safety when compared to the counterpart . Both of these prodrugs were first created to cover the polar phosphonic acid group on tenofovir by using a novel oxycarbonyloxymethyl linkers to improve the oral bioavailability and intestinal diffusion. Tenofovir alafenamide is an alanine ester form characterized for presenting low systemic levels but high intracellular concentration. It has been reported to produce a large antiviral efficacy at doses ten times lower than tenofovir disoproxil. Tenofovir alafenamide is indicated to treat chronic hepatitis B, treat HIV-1, and prevent HIV-1 infections. Tenofovir alafenamide was developed by Gilead Sciences Inc and granted FDA approval on 5 November 2015. |
| PubChem ID: | -- |
| CasNo: | -- |
| Repositioning for NAFLD: | Yes |
| SMILES: | S1C[C@H](O[C@H]1CO)n1cc(F)c(nc1=O)N.[P@@](=O)(Oc1ccccc1)(N[C@@H](C)C(=O)OC(C)C)CO[C@@H](Cn1c2ncnc(N)c2nc1)C.N(c1c(cc(cc1C)/C=C/C#N)C)c1nc(Nc2ccc(cc2)C#N)ncc1 |
| Structure: |
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| InChiKey: | GHWBYIZAYFIRPA-PPEAAZTNSA-N |
| Molecular Weight: | 1090.153 |
| DrugBank Targets: | Reverse transcriptase/RNaseH inhibitor; Reverse transcriptase inhibitor; DNA polymerase inhibitor |
| DrugBank MoA: | Tenofovir alafenamide presents 91% lower plasma concentration with an intracellular presence of about 20-fold higher when compared to . This is due to its prolonged systemic exposure and its higher intracellular accumulation of the active metabolite tenofovir diphosphate. Tenofovir alafenamide accumulates more in peripheral blood mononuclear cells compared to red blood cells. Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase, causing chain termination and the inhibition of viral synthesis. To know more about the specific mechanism of action of the active form, please visit the drug entry of . |
| DrugBank Pharmacology: | Tenofovir alafenamide has been shown to be a potent inhibitor of hepatitis B viral replication. Tenofovir alafenamide presents a better renal tolerance when compared with the counterpart . This improved safety profile seems to be related to a lower plasma concentration of tenofovir. In clinical trials, tenofovir alafenamide was shown to present 5-fold more potent antiviral activity against HIV-1 when compared to tenofovir disoproxil. |
| DrugBank Indication: | Tenofovir alafenamide is indicated for the treatment of chronic hepatitis B in adult patients with compensated liver disease. In combination with and other antiretrovirals, it is indicated for the treatment of HIV-1 infection in adolescent and adult patients with a weight higher than 35 kg. This combination is also indicated to prevent HIV-1 infections in high risk adolescent and adult patients, excluding patients at risk from receptive vaginal sex. When combined with antiretrovirals other than protease inhibitors that require a CYP3A inhibitor, it can be used to treat pediatric patients weighing 25-35 kg. In the combination product with emtricitabine and , tenofovir alafenamide is considered as a complete regimen for the treatment of HIV-1 infection in treatment-naive patients or in patients virologically suppressed for at least 3 months with no history of treatment failure. Additionally, the combination product including , , emtricitabine and tenofovir alafenamide and the combination product including emtricitabine, and tenofovir alafenamide can be used in the treatment of HIV-1 infection in patients older than 12 years with no previous antiretroviral therapy history or who are virologically suppressed for at least 6 months with no history of treatment failure. The combination product including , cobicistat, emtricitabine, and tenofovir alafenamide is indicated for the treatment of HIV-1 infection in adults without prior antiretroviral therapy or in patients virologically suppressed for 6 months and no reported resistance to darunavir or tenofovir. |
| Targets: | -- |
| Therapeutic Category: | -- |
| Clinical Trial Progress: | Phase 4 on-going (ChiCTR1900023153) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0747 | ACTRN12619000701123 | Phase 3 | Not Recruiting | No Results Available | 09/05/2019 | 15 July 2019 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00232 | 35173677 | Front Endocrinol (Lausanne) | Validation of Controlled Attenuation Parameter Measured by FibroScan as a Novel Surrogate Marker for the Evaluation of Metabolic Derangement. | Details |
| A00623 | 35024308 | Acta Pharm Sin B | Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver. | Details |
| A00933 | 34925033 | Front Pharmacol | Activation of TAF9 via Danshensu-Induced Upregulation of HDAC1 Expression Alleviates Non-alcoholic Fatty Liver Disease. | Details |
| A01381 | 34768440 | J Clin Med | Prothrombotic and Inflammatory Markers in Elderly Patients with Non-Alcoholic Hepatic Liver Disease before and after Weight Loss: A Pilot Study. | Details |
| A02041 | 34522873 | EClinicalMedicine | Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART). | Details |
| A02179 | 34472683 | Hepatol Res | MAFLD: Renovation of clinical practice and disease awareness of fatty liver. | Details |
| A02585 | 34322121 | Front Immunol | CD8+ T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs. | Details |
| A02652 | 34297733 | PLoS One | Long working hours are associated with a higher risk of non-alcoholic fatty liver disease: A large population-based Korean cohort study. | Details |
| A03774 | 33868403 | J Oncol | The Gene Signature Associated with Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. | Details |
| A03882 | 33833819 | Evid Based Complement Alternat Med | The Exploration of Novel Pharmacophore Characteristics and Multidirectional Elucidation of Structure-Activity Relationship and Mechanism of Sesquiterpene Pyridine Alkaloids from Tripterygium Based on Computational Approaches. | Details |
| A04576 | 33574823 | Front Immunol | Self-Nucleic Acid Sensing: A Novel Crucial Pathway Involved in Obesity-Mediated Metaflammation and Metabolic Syndrome. | Details |
| A04907 | 33455863 | Trends Endocrinol Metab | Role of Macrophages in the Endocrine System. | Details |
| A05580 | 33200549 | Basic Clin Pharmacol Toxicol | Salsalate reverses metabolic disorders in a mouse model of non-alcoholic fatty liver disease through AMPK activation and caspase-6 activity inhibition. | Details |
| A06238 | 32958032 | Orphanet J Rare Dis | Consensus clinical management guidelines for Alström syndrome. | Details |
| A06275 | 32945042 | Cancer Sci | System biology analysis reveals the role of voltage-dependent anion channel in mitochondrial dysfunction during non-alcoholic fatty liver disease progression into hepatocellular carcinoma. | Details |
| A06318 | 32931733 | Cell | Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output. | Details |
| A06521 | 32841652 | J Allergy Clin Immunol | Regulating metabolic inflammation by nutritional modulation. | Details |
| A07295 | 32553151 | Lancet Gastroenterol Hepatol | Novel antisense inhibition of diacylglycerol O-acyltransferase 2 for treatment of non-alcoholic fatty liver disease: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. | Details |
| A07902 | 32316984 | BMC Health Serv Res | Protocol for a randomised trial testing a community fibrosis assessment service for patients with suspected non-alcoholic fatty liver disease: LOCal assessment and triage evaluation of non-alcoholic fatty liver disease (LOCATE-NAFLD). | Details |
| A08055 | 32267269 | Food Funct | A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice. | Details |