A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Sequential Single Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of Subcutaneously and Intramuscularly Administered TMB-607 in HIV-Negative Volunteers

The study is a Phase 1, randomized, double-blinded, placebo-controlled, sequential single dose escalation safety, tolerability and pharmacokinetic study of subcutaneous and intramuscular TMB-607 administered to HIV-negative volunteers.

Start Date21 Nov 2016

Sponsor / Collaborator

TaiMed Biologics, Inc.

100 Clinical Results associated with PPL-100

100 Translational Medicine associated with PPL-100

100 Patents (Medical) associated with PPL-100

Literatures (Medical) associated with PPL-100

01 Nov 2022·Journal of Environmental Quality

Changes in microbial communities in soil treated with organic or conventional N sources

Article

Author: Sintim, Henry ; Ouyang, Yang ; Norton, Jeanette ; Woodruff, Lisa ; Habteselassie, Mussie

AbstractDespite the extensive use of N fertilizers in agricultural soils, we are yet to fully understand their impact on soil microbial communities that mediate important soil processes. A 3‐yr field study was undertaken in Georgia, where sweet corn (Zea mays L.) was grown under conventional or organic systems. Nitrogen (N) was supplied with ammonium sulfate at 112 kg N ha–1 (AS100) or 224 kg N ha–1 (AS200) or a combination of poultry litter, cover crop, and blood meal at 112 kg N ha–1 (PL100) or no N (control). Soil samples were collected from field plots to assess the impact of treatments on bacteria, fungi, and ammonia oxidizers using molecular methods that targeted 16S RNA, ITS2, and amoA genes, respectively. Treatment had significant impact on bacterial but not fungal composition. The AS200 significantly changed the relative abundances of Verrucomicrobia and Acidobacteria and decreased bacterial alpha diversity as compared with control. Beta‐diversity analysis showed clear separation of microbial communities in AS200 vs. control and PL100. The abundance of ammonia‐oxidizing bacteria (AOB) was more responsive to N input than ammonia oxidizing‐archaea. It was also significantly and positively correlated with nitrification potential and soil nitrate with increasing N rates, indicating AOB's dominance in driving nitrification under high N input. Overall, the results indicated that AS200 changed bacterial composition and diversity, suggesting corresponding changes in soil processes related to N mineralization and nitrification. Understanding such changes in microbial communities can help us predict changes in soil processes to adopt sustainable management systems.

13 Oct 2021·Journal of Biomolecular Structure and Dynamics

Possibility of HIV-1 protease inhibitors-clinical trial drugs as repurposed drugs for SARS-CoV-2 main protease: a molecular docking, molecular dynamics and binding free energy simulation study

Article

Author: Ancy, Iruthayaraj ; Sivanandam, Mugudeeswaran ; Kumaradhas, Poomani

Initially, the SARS-CoV-2 virus was emerged from Wuhan, China and rapidly spreading across the world and urges the scientific community to develop antiviral therapeutic agents. Among several strategies, drug repurposing will help to react immediately to overcome the COVID-19 pandemic. In the present study, we have chosen two clinical trial drugs against HIV-1 protease namely, TMB607 and TMC310911 to use as the inhibitors of SARS-CoV-2 main protease (M^pro) enzyme. To make use of these two inhibitors as the repurposed drugs for COVID-19, it is essential to know the molecular basis of the binding mechanism of these two molecules with the SARS-CoV-2 M^pro. To understand the binding mechanism, we have performed molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations against the SARS-CoV-2 M^pro. The docking results indicate that both molecules form intermolecular interactions with the active site amino acids of M^pro enzyme. However, during the MD simulations, TMB607 forms strong interaction with the key amino acids of M^pro, and remains intact. The RMSD and RMSF values of both complexes were stable throughout the MD simulations. The MM-GBSA binding free energy values of both complexes are -43.7 and -34.9 kcal/mol, respectively. This in silico study proves that the TMB607 molecule binds strongly with the SARS-CoV-2 M^pro enzyme and it may be suitable for the drug repurposing of COVID-19 and further drug designing.Communicated by Ramaswamy H. Sarma.

14 Dec 2017·ACS Medicinal Chemistry LettersQ3 · MEDICINE

Design and Synthesis of Piperazine Sulfonamide Cores Leading to Highly Potent HIV-1 Protease Inhibitors

Q3 · MEDICINE

Article

Author: Holloway, M. Katharine ; Stamford, Andrew W. ; Morris, William ; Schulz, Jurgen ; Carroll, Steven S. ; Manikowski, Jesse J. ; Fay, John F. ; Hu, Bin ; Williams, Peter D. ; Miller, Michael D. ; Morriello, Gregori J. ; Chang, Lehua ; Min, Xu ; Diamond, Tracy L. ; Ji, Tao ; Keertikar, Kartik ; McCauley, John A. ; Ballard, Jeanine E. ; Dwyer, Michael P. ; Zhong, Bin ; Bahnck-Teets, Carolyn ; Chu, Xin-Jie ; Bungard, Christopher J. ; Crespo, Alejandro ; Bennett, David J. ; Waddell, Sherman T. ; Loughran, H. Marie ; Wiscount, Catherine M. ; Su, Hua-Poo

Using the HIV-1 protease binding mode of MK-8718 and PL-100 as inspiration, a novel aspartate binding bicyclic piperazine sulfonamide core was designed and synthesized. The resulting HIV-1 protease inhibitor containing this core showed an 60-fold increase in enzyme binding affinity and a 10-fold increase in antiviral activity relative to MK-8718.

100 Deals associated with PPL-100

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 1	-	Ambrilia Biopharma, Inc.	-
HIV Infections	Phase 1	-	Ambrilia Biopharma, Inc.	-

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