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Biochemical and Structural Studies of Protein Tyrosine Phosphatase PTP‐PEST (PTPN12) in Search of Small Molecule Inhibitors

Chemical Biology and Drug Design

In this study, we aimed to investigate small molecules that could potentially inhibit PTP-PEST for further development of PTP-PEST inhibitors. Till now only a few inhibitors are currently being studied in the inhibition of PTP-PEST, majorly belonging to the class of metal-based drugs.

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Redirecting the pioneering function of FOXA1 with covalent small molecules

Covalent Modifiers

Here, we report the chemical proteomic discovery of electrophilic small molecules that stereoselectively and site-specifically bind the pioneer TF, FOXA1, at a cysteine (C258) within the forkhead DNA-binding domain. Chemical probes are lacking for pioneer TFs, which has hindered their mechanistic investigation in cells.

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Small Molecules Evolve

Drug Hunter

Small molecule drugs make up most of the drugs we take conveniently as pills, including painkillers like ibuprofen (Advil), antibiotics like penicillin and amoxicillin, or cholesterol-lowering drugs like atorvastatin (Lipitor). The small molecules drugs of today look nothing like the molecules of the 1970s.

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Site-Specific Molecular Glues for the 14-3-3/Tau pS214 ProteinProtein Interaction via Reversible Covalent Imine Tethering

Covalent Modifiers

Modulating PPIs with small molecules has gained increasing attention in drug discovery, particularly targeting the 14-3-3 protein family, which interacts with several hundred client proteins and plays a central role in cellular networks.

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Flagship’s latest startup aims to take the guesswork out of small molecule drugs

BioPharma Drive: Drug Pricing

Empress Therapeutics claims its technology allows it to identify chemical drug candidates faster and more reliably. It has $50 million from Flagship to prove it can.

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Redirecting the pioneering function of FOXA1 with covalent small molecules

Covalent Modifiers

Our findings reveal a striking plasticity underpinning the pioneering function of FOXA1 that can be controlled by small molecules. Motif analysis supports a mechanism where the ligands relax the canonical DNA-binding preference of FOXA1 by strengthening interactions with suboptimal sequences in predicted proximity to C258.

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Selective Covalent Inhibiting JNK3 by Small Molecules for Parkinson's Diseases

Covalent Modifiers

Liang Ouyang, Wen Shuai, Panpan Yang, Huan Xiao, Yumeng Zhu, Faqian Bu, Aoxue Wang, Qiu Sun, Guan Wang Angewandte Chemie 2024 e202411037 [link] c-Jun N-terminal kinases (JNKs) including JNK1/2/3 are key members of mitogen-activated protein kinase family.