Patients who complete study T1249-102 (must be currently failing a T-20 containing regimen to participate in this study) will receive T-1249 at a dose of 200mg daily in combination with a background antiretroviral regimen for 96 weeks. Only patients that participated in study T1249-102 can participate in study T1249-105.

开始日期-

申办/合作机构

Trimeris, Inc.

100 项与 Tifuvirtide 相关的临床结果

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100 项与 Tifuvirtide 相关的转化医学

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100 项与 Tifuvirtide 相关的专利（医药）

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项与 Tifuvirtide 相关的文献（医药）

2018-04-01·Journal of Biological Chemistry2区 · 生物学

Exceptional potency and structural basis of a T1249-derived lipopeptide fusion inhibitor against HIV-1, HIV-2, and simian immunodeficiency virus

2区 · 生物学

Article

作者: He, Yuxian ; Ding, Xiaohui ; Wang, Xinquan ; Zhu, Yuanmei ; Cui, Sheng ; Chong, Huihui ; He, Jinsheng ; Zhang, Xiujuan

Enfuvirtide (T20) is the only viral fusion inhibitor approved for clinical use, but it has relatively weak anti-HIV activity and easily induces drug resistance. In succession to T20, T1249 has been designed as a 39-mer peptide composed of amino acid sequences derived from HIV-1, HIV-2, and simian immunodeficiency virus (SIV); however, its development has been suspended due to formulation difficulties. We recently developed a T20-based lipopeptide (LP-40) showing greatly improved pharmaceutical properties. Here, we generated a T1249-based lipopeptide, termed LP-46, by replacing its C-terminal tryptophan-rich sequence with fatty acid. As compared with T20, T1249, and LP-40, the truncated LP-46 (31-mer) had dramatically increased activities in inhibiting a large panel of HIV-1 subtypes, with IC₅₀ values approaching low picomolar concentrations. Also, LP-46 was an exceptionally potent inhibitor against HIV-2, SIV, and T20-resistant variants, and it displayed obvious synergistic effects with LP-40. Furthermore, we showed that LP-46 had increased helical stability and binding affinity with the target site. The crystal structure of LP-46 in complex with a target surrogate revealed its critical binding motifs underlying the mechanism of action. Interestingly, it was found that the introduced pocket-binding domain in LP-46 did not interact with the gp41 pocket as expected; instead, it adopted a mode similar to that of LP-40. Therefore, our studies have provided an exceptionally potent and broad fusion inhibitor for developing new anti-HIV drugs, which can also serve as a tool to exploit the mechanisms of viral fusion and inhibition.

2017-09-01·Biophysical Chemistry4区 · 生物学

Molecular dynamics simulations of T-2410 and T-2429 HIV fusion inhibitors interacting with model membranes: Insight into peptide behavior, structure and dynamics

4区 · 生物学

Article

作者: Mavioso, I C V C ; Palace Carvalho, A J ; Martins do Canto, A M T ; de Andrade, V C R

T-2410 and T-2429 are HIV fusion inhibitor peptides (FI) designed to present a higher efficiency even against HIV strains that developed resistance against other FIs. Similar peptides were shown to interact with model membranes both in the liquid disordered phase and in the liquid ordered state. Those results indicated that such interaction is important to function and could be correlated with their effectiveness. Extensive molecular dynamics simulations were carried out to investigate the interactions between both T-2410 and T-2429 with bilayers of pure 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and a mixture of POPC/cholesterol (Chol) (1:1). It was observed that both peptides interact strongly with both membrane systems, especially with the POPC/Chol systems, where these peptides show the highest number of H-bonds observed so far. T-2410 and T-2429 showed higher extent of interaction with bilayers when compared to T-20 or T-1249 in previous studies. This is most notable in POPC/Chol membranes where, although able to form H-bonds with Chol, they do so to a lesser extent than T-1249 does, the latter being the only FI peptide so far that was observed to form H-bonds with Chol. This behavior suggests that interaction of FI peptides with rigid Chol rich membranes may not be as dependent from peptide/Chol H-bond formation as previous results of T-1249 behavior led to believe. As in other similar peptides, the higher ability to interact with membranes shown by T-2410 and T2429 is probably correlated with its higher inhibitory efficiency.

2016-06-01·Drug Delivery and Translational Research3区 · 医学

Sustained release of the candidate antiretroviral peptides T-1249 and JNJ54310516-AFP from a rod insert vaginal ring

3区 · 医学

Article

作者: Clarke, Aileen ; Malcolm, R Karl ; van Roey, Jens ; O'Hara, Marc ; Murphy, Diarmaid J ; Amssoms, Katie ; Pille, Geert

Administration of biomacromolecular drugs in effective quantities from conventional vaginal rings is hampered by poor drug permeability in the polymers from which rings are commonly constructed. Here, we report the formulation development and testing of rod insert rings for sustained release of the candidate antiretroviral peptides T-1249 and JNJ54310516-AFP (JNJ peptide), both of which have potential as HIV microbicides. Rod inserts were prepared comprising antiviral peptides T-1249 or JNJ peptide in combination with a hydrophilic excipient (sodium chloride, sodium glutamate, lactose or zinc acetate) dispersed at different loadings within a medical grade silicone elastomer. The inserts were tested for weight change and swelling when immersed in simulated vaginal fluid (SVF). Dye migration into the inserts was also assessed visually over 28 days. In vitro release of T-1249 and JNJ peptide from rings containing various insert types was tested. Weight change and degree of swelling of rods immersed in SVF was dependent on the type and concentration of excipient present. The rods displayed the following rank order in terms of weight change: sodium glutamate > zinc acetate ≈ sodium chloride > lactose. The weight change and degree of swelling of the inserts did not correlate with the level of dye uptake observed. In vitro release of T-1249 was improved through addition of lactose, sodium chloride and sodium glutamate, while release of JNJ peptide was improved through addition of sodium chloride or sodium glutamate. Sustained release of hydrophobic peptides can be achieved using a rod insert ring design formulated to include a hydrophilic excipient. Release rates were dependent upon the type of excipient used. The degree of release improvement with different inserts partially reflects their ability to imbibe surrounding fluid and swell in aqueous environments.

100 项与 Tifuvirtide 相关的药物交易

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