Accès ouvert
2026
article
OpenAlex
Robert E. Thompson, Aditya J. Desai, Dmitri Pissarnitski, Dan Shao et autres
High Resolution Image Download MS PowerPoint Slide Peptide agonists of the glucagon-like peptide 1 receptor (GLP-1R) have demonstrated clinical efficacy for the management of type 2 diabetes and promote weight loss in addition to glucose-dependent insulin secretion. Monomolecular dual- or triagonists that …
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2026
conference-abstract
OpenAlex
Diwakar R. Pattabiraman, Brandon Nicolay, Pieter Beerepoot, Kelsey Barrasso et autres
Abstract Prostate cancer (PCa) remains largely driven by the androgen receptor (AR) even in castration-resistant settings where AR signaling is maintained through various genetic mechanisms including mutations in the androgen binding pocket and amplifications in the AR locus leading to overexpression of …
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2026
article
OpenAlex
Xiaoshen Ma, David L. Sloman, Timothy J. Henderson, David Jonathan Bennett et autres
KRAS, a significant oncology target, has been challenging to develop drugs for until recent discoveries of KRAS G12C mutant-specific covalent inhibitors, including MK-1084. This article describes efforts toward the discovery of KRAS G12D mutant-specific inhibitors and how synthetic innovations and structure-based drug …
us, gb, jp
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2025
conference-abstract
OpenAlex
Diwakar R. Pattabiraman, Brandon Nicolay, Pieter Beerepoot, Kelsey Barrasso et autres
Abstract Stabilized helical peptides (Helicons™) have been demonstrated to bind to intracellular targets at binding sites on proteins that are generally regarded as undruggable e.g., FOG-001 inhibits the b-catenin-TCF4 interaction and is currently being evaluated in the clinic in advanced solid tumors. …
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Accès ouvert
2024
article
OpenAlex
Xiaoshen Ma, David L. Sloman, Ruchia Duggal, Kenneth D. Anderson et autres
Oncogenic mutations in the RAS gene account for 30% of all human tumors; more than 60% of which present as KRAS mutations at the hotspot codon 12. After decades of intense pursuit, a covalent inhibition strategy has enabled selective targeting of this …
us, gb
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2023
conference-abstract
OpenAlex
Matthew L. Maddess, David L. Sloman, Xiaoshen Ma, Anandan Palani et autres
Abstract KRAS mutations are the predominant oncogenic drivers in multiple indications including non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC). KRAS has long been considered a challenging target due to the perceived lack of druggable binding pockets …
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Accès ouvert
2022
article
OpenAlex
Chunhui Huang, Anandan Palani, Zhiqiang Yang, Vijay Reddy et autres
The combination of insulin and incretin-based therapies has emerged as a potential promising tactic for the treatment of diabetes. Here we report the first example of a unimolecular triagonist to simultaneously target insulin, GLP-1, and glucagon receptors, aiming for better glycemic control …
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Accès ouvert
2022
article
OpenAlex
Anandan Palani, Andrea R. Nawrocki, Federica Orvieto, Elisabetta Bianchi et autres
Peptide-based analogues of the gut-derived incretin hormone, glucagon-like peptide 1 (GLP1), stimulate insulin secretion in a glucose-dependent manner. Currently marketed GLP1 receptor (GLP1R) agonists are safe and effective in the management of Type 2 diabetes but often offer only modest weight loss. …
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Accès ouvert
2021
article
OpenAlex
Gregory L. Adams, Parul S. Pall, Steven M. Grauer, Xiaoping Zhou et autres
Inhibitor cystine knot peptides, derived from venom, have evolved to block ion channel function but are often toxic when dosed at pharmacologically relevant levels in vivo . The article describes the design of analogues of ProTx-II that safely display systemic in vivo …
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Accès ouvert
2021
article
OpenAlex
Derun Li, Hongjun Zhang, Thomas W. Lyons, Min Lu et autres
Comprehensive synthetic strategies afforded a diverse set of structurally unique bicyclic proline-containing arginase inhibitors with a high degree of three-dimensionality. The analogs that favored the Cγ-exo conformation of the proline improved the arginase potency over the initial lead. The novel synthetic strategies …
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Accès ouvert
2021
article
OpenAlex
Min Lu, Hongjun Zhang, Derun Li, Matthew C. Childers et autres
High Resolution Image Download MS PowerPoint Slide Recent data suggest that the inhibition of arginase (ARG) has therapeutic potential for the treatment of a number of indications ranging from pulmonary and vascular disease to cancer. Thus, high demand exists for selective small …
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Accès ouvert
2020
article
OpenAlex
Mihirbaran Mandal, Alexei V. Buevich, John P. Caldwell, Lynn A. Hyde et autres
Abstract Herein, we disclose three structurally differentiated γ-secretase modulators (GSMs) based on an oxadiazine scaffold. The analogues from series I potently inhibit the generation of Aβ42 in vitro when the substituents at 3 and 4 positions of the oxadiazine moiety adopt an …
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