Covalent Modifiers

OCTOBER 10, 2023

Ebert, Nathanael Gray bioRxiv 2023 [link] Small molecules that can induce protein degradation by inducing proximity between a desired target and an E3 ligase have the potential to greatly expand the number of proteins that can be manipulated pharmacologically. Rutter, Cyrus Y. Jin, Michelle Y. Wang, Shawn Xu, Anna M.

Targeted Protein Degradation 208

Targeted Protein Degradation Small Molecule 208

Broad Institute

JANUARY 6, 2025

Advancements in small-molecule chemistry have given us a real opportunity to come up with precise approaches to correct, modify, or activate genetic variants, said Ramnik Xavier , a core institute member, director of the Immunology Program , and co-director of the Infectious Disease and Microbiome Program at the Broad.

Disease 139

Disease Research DNA Small Molecule 139

Chemical Biology and Drug Design

JANUARY 29, 2024

To aid the medicinal chemist in the design of sPLA 2 inhibitors, this review selected four human sPLA 2 s and presented the characteristics of the bound inhibitors that are considered key for high-affinity interaction. Due to their roles in inflammation, the sPLA 2 enzymes are of much medicinal interest.

Small Molecule 100

Small Molecule Immune Response Treatment Disease 100

Drug Hunter

JUNE 29, 2023

The talk covered: Theoretical advantages of targeted protein degradation over traditional small molecules Recent highlights throughout the industry illustrating these advantages Areas to watch in targeted protein degradation on the horizon Some of the highlights mentioned in the talk include: IV STAT3 degraders from Kymera Therapeutics (e.g.

Targeted Protein Degradation 221

Targeted Protein Degradation Small Molecule Drugs 221

Covalent Modifiers

JULY 25, 2024

We have integrated structural and quantitative proteomics with biochemical assays to decipher the mode of action of covalent USP30 inhibition by a small molecule containing a cyanopyrrolidine reactive group, USP30-I-1.

Biochemical Assays 182

Biochemical Assays Small Molecule Treatment Disease 182

ASPET

JULY 13, 2023

Dynasore and dyngo-4a, small molecules developed to inhibit the GTPase activity of classic dynamins DNM1, DNM2 and DNM3, but not mdivi-1, a specific inhibitor of DNM1L, protect corneal epithelial cells exposed to the oxidant tert-butyl hydroperoxide (tBHP).

Small Molecule 100

Small Molecule Treatment 100

Covalent Modifiers

JANUARY 17, 2024

Here we use 31P NMR to delineate the differences in state 1 and state 2 populations present in wild-type (WT) and common KRAS oncogenic mutants (G12C, G12D, G12V, G13D, and Q61L) bound to its natural substrate GTP or a commonly used nonhydrolyzable analogue GppNHp.

Small Molecule 195

Small Molecule Regulations Drugs 195

Chemical Biology and Drug Design

NOVEMBER 20, 2023

Given the abnormally high expression of c-Maf in most MM patients, targeting c-Maf presents an attractive therapeutic approach for treating MM malignancies. Abstract Multiple myeloma (MM) is a prevalent plasma cell malignancy in the blood system that remains incurable.

Small Molecule 100

Small Molecule Protein Expression FDA Approval FDA 100

The ChEMBL-og

OCTOBER 23, 2024

This project builds upon the PDBeKnowledge Base (PDBe-KB) resource and combines structural, functional, and biochemical information for small molecules and their targets. By integrating CSD identifiers in UniChem, it is now easier to identify the availability of crystal structures that contain a specific molecule of interest.

Small Molecule 117

Small Molecule Drugs Research Science 117

Metabolite Tales Blog

JANUARY 23, 2024

Metabolism of 2023 FDA Approved Small Molecules – PART 1 By Julia Shanu-Wilson 2023 was a fruitful year for drug approvals by the FDA, with a crop of 34 small molecules out of a total of 55 new drugs [1]. References [1] 2023 Novel Small Molecule FDA Drug Approvals.

Small Molecule 52

Small Molecule FDA Approval FDA Pharmacokinetics 52

Dark Matter Blog

AUGUST 27, 2020

A few years ago, at Arrakis Therapeutics, we set out to conquer a strange new territory, drugging RNA structures with small molecules. Dramatic discoveries of small molecules targeting SMN2 Prior to those outstanding therapeutic achievements, in 2015, a group from Novartis published an important paper in Nature Chemical Biology.

Small Molecule 52

Small Molecule RNA Clinical Trials Drugs 52

Metabolite Tales Blog

APRIL 4, 2023

Metabolism of 2022 FDA approved small molecule drugs part 2 Mixing it Up By Julia Shanu-Wilson In Part 1 of this topic we looked at metabolism of the small molecule drugs approved by the FDA in 2022 that were mediated by CYP3A4. Oxidation of adagrasib occurs on the methylpyrrolidine group 4. Gut 1996; 38: 439-446.

Small Molecule 52

Small Molecule FDA Approval FDA Drugs 52

Covalent Modifiers

MAY 29, 2023

Here we present a global map of a human sulfenome that is susceptible to covalent modification by members of a nucleophilic fragment library. More than 500 liganded sulfenic acids were identified on proteins across diverse functional classes, and, of these, more than 80% were not targeted by electrophilic fragment analogs.

Small Molecule 130

Small Molecule DNA 130

ASPET

JULY 19, 2024

Here we design an assay to screen a compound library of small molecules inhibitors. Four compounds were identified as potential small molecule inhibitors one of which, BM-8372, demonstrated significant effect in platelet aggregation assays.

Small Molecule 100

Small Molecule Disease Research 100

Covalent Modifiers

MAY 10, 2023

In summary, we present a chemical strategy for the systematic discovery of condensate-modulating covalent small molecules. Among these, we functionally validate G3BP1 Y40, located in the NTF2 dimerization domain, as a ligandable site that can disrupt arsenite-induced SG formation in cells.

Small Molecule 130

Small Molecule RNA 130

Conversations in Drug Development Trends

MAY 30, 2024

Other researchers are investigating approaches that use AAV-mediated trophic support and antibody-based therapies, such as vaccines and small molecule drugs, to modify various protein expressions. The post Present Treatments & Hopeful Future Directions for ALS Pharmacotherapies appeared first on Worldwide Clinical Trials.

Treatment 81

Treatment Clinical Trials Small Molecule Therapies 81

The Pharma Data

JULY 29, 2021

Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), and Kumquat Biosciences today announced an exclusive collaboration focused on the discovery, development and commercialization of potential novel small molecules that stimulate tumor-specific immune responses.

Small Molecule 52

Small Molecule Immune Response Research Laboratories Laboratories 52

Drug Target Review

JUNE 15, 2023

In this article Drug Target Review’s Izzy Wood spoke to Sam Hasson, Director of Target Biology at Rgenta Therapeutics, a biotech firm in Massachusetts, US, that aims to develop small molecule therapeutics to target RNA processing. It is somewhat like how PROTACs have changed the perspective on what is a tractable therapeutic target.

RNA 96

RNA Small Molecule Disease Assay Development 96

DrugBank

JULY 24, 2024

These multifunctional small molecules are like tiny spies, hijacking the body’s natural protein degradation system to remove unwanted proteins. Multifunctional Small Molecules and Peptides Beyond PROTACs, there are other exciting tools in the new drug discovery toolbox.

Small Molecule 98

Small Molecule Drugs Clinical Trials Therapies 98

ASPET

OCTOBER 12, 2023

The self-assembled structures can be small molecules, polymers, peptides, proteins, which can be utilized and functionalized to achieve tailored release and target specific cells, tissues, or organs. Different SNs approaches and recent literature reviews on peptide delivery are also presented to the readers.

Therapies 100

Therapies Small Molecule Treatment Drugs 100

Atomwise Blog

MARCH 9, 2022

At the American Chemical Society Spring National Meeting & Expo, Atomwise members were selected to present their research and work. Learn what our Atoms have been working on below and visit Atomwise at ACS Spring 2022 National Meeting for other presentation sessions.

Small Molecule 52

Small Molecule Research 52

Chemical Biology and Drug Design

JUNE 7, 2023

In the present study, we got the SIRT7 protein structure from Alpha Fold2 Database and performed structure-based virtual screening to develop specific SIRT7 inhibitors using the SIRT7 inhibitor 97,491 interaction mechanism. ZINC000001910616 and ZINC000014708529, two of our leading compounds, showed strong interactions with SIRT7.

Small Molecule 100

Small Molecule Treatment Research 100

Drug Target Review

JULY 6, 2023

1 TPD is expected to challenge undruggable proteins, which are highly difficult to target by conventional small molecules. 1 The concept of TPD was first demonstrated with a heterobifunctional small molecule to degrader a protein of interest in the early 2000s.

Targeted Protein Degradation 98

Targeted Protein Degradation Small Molecule Clinical Trials Science 98

Chemical Biology and Drug Design

MAY 11, 2023

In discovery of novel small molecules that interfere PCSK9/LDLR protein–protein interaction (PPI), structural modification was performed based on our previously derived compounds. It is significant that molecules D28 and D29 exhibited potential for the treatment of hyperlipidemia in current in vitro investigations.

Small Molecule 100

Small Molecule Treatment Research 100

Drug Target Review

APRIL 7, 2025

Advancements in screening technologies for small-molecule drug discovery including cellular assays, computational screening, and biophysics-based methods enhanced by structural biology breakthroughs have improved screening hit rates and facilitated the identification of drug candidates for previously undruggable targets.

Fragment Screening 52

Fragment Screening Drugs Small Molecule Biophysical Assays 52

DrugBank

MAY 22, 2024

In the dynamic world of drug discovery, the notion of "undruggable" targets presents both a significant challenge and an intriguing frontier for researchers and pharmaceutical companies. Strategies to Tackle PPIs Despite these challenges, some wins in targeting PPIs with small molecules have emerged.

Small Molecule 96

Small Molecule RNA DNA Pharmaceutical Companies 96

ASPET

SEPTEMBER 28, 2023

Indeed, recognition of the role of SGK-1 in regulation of cell survival and proliferation has led to introduction of a number of small-molecule inhibitors for some types of cancer. The family of serum-glucocorticoid-regulated kinase (SGK) consists of three paralogs- SGK-1, SGK-2 and SGK-3 with SGK-1 being the better studied.

Regulations 100

Regulations Small Molecule Disease Research 100

Molecular Design

DECEMBER 31, 2024

My pulse will be quickenin' With each drop of strychnine We feed to a pigeon It just takes a smidgin To poison a pigeon in the park Tom Lehrer, Poisoning Pigeons in the Park | video ** Ill be reviewing the H2024 study (Occurrence of Natural Selection in Successful Small Molecule Drug Discovery) in this post.

Small Molecule 85

Small Molecule Drugs Production Science 85

DrugBaron

FEBRUARY 7, 2022

Finding small molecule drugs is much harder than finding a needle in a haystack – discovering the right arrangement of atoms to bind precisely to a protein target to elicit a particular response is a problem of vast dimensionality. Yet the situation with small molecules is even worse.

Small Molecule 100

Small Molecule Synthetic Chemistry Pharma Companies Pharmacokinetics 100

Drug Target Review

APRIL 7, 2025

However, standard preclinical safety assessment studies may not accurately predict adverse events in humans, particularly with emerging modalities like precision medicine targeting human antigens or genes not present in preclinical species. For use as endpoints, biomarkers must be correlated to a valid clinical outcome.

Clinical Development 59

Clinical Development Clinical Trials Clinical Pharmacology Trials 59

Drug Target Review

SEPTEMBER 25, 2024

4 Another related and well described non-oncogene resistance mechanism is the histological transformation of EGFR-mutated non-small cell lung cancer (NSCLC) to small-cell lung cancer upon treatment with an EGFR inhibitor. 5 Here, the original oncogene is still present but the transdifferentiated cancer cells are less dependent on it.

Small Molecule 105

Small Molecule Therapies Regulations Treatment 105

The Strateos Blog: Drug Discovery

DECEMBER 13, 2021

We are excited to share that Strateos’ SVP of Strategy & Operations, Daniel Sipes, will be delivering a presentation entitled Accelerating Medicinal Chemistry Cycle Times Through Cloud-Accessible Smart Automated Labs at the upcoming 2022 Society for Laboratory Automation and Screening Conference & Exhibition between February 5-9th.

Biochemical Assays 52

Biochemical Assays Small Molecule Laboratories Science 52

The Pharma Data

JANUARY 5, 2021

(Nasdaq: RLAY) is scheduled to present at the 39th Annual J.P. The presentation will be webcast live and may be accessed from the Investor page of Relay’s website under Events and Presentations. An archived replay of the webcast will be available for at least 30 days following the presentation. About Relay Therapeutics.

Small Molecule 40

Small Molecule Therapies Drugs 40

Drug Target Review

AUGUST 25, 2023

However, in tissues where the 3 Hs are not present, the small molecule has anti-toxicity activity through 1) direct inhibition of the NLRP3 inflammasome, an inflammation starter and perpetuator, and 2) upregulation of the master antioxidant transcription factor, Nrf2.

Small Molecule 98

Small Molecule Virus International Clinical Trials 98

The Pharma Data

NOVEMBER 18, 2020

Presentations to highlight the OBI-833 Phase 1 clinical study results in non-small cell lung cancer (NSCLC) and the dose escalation cohort. These results will be presented by the lead investigators of OBI Pharma’s novel anti-Globo H therapeutic cancer vaccine, OBI-833. ” Presentation number: 397P / Poster: ID 680.

Vaccine 52

Vaccine Small Molecule Immune Response Hospitals 52

Drug Target Review

OCTOBER 4, 2023

Groundbreaking strategies like proteolysis-targeting chimeric molecules (PROTACs) are also being explored. 6 Combining the effect of payloads with different mechanisms of action – an approach that revolutionised small molecule chemotherapy – also holds the promise of enhanced therapeutic activity for ADCs. 161 , 416–432 (2019).

Small Molecule 126

Small Molecule Drugs Immune Response Targeted Protein Degradation 126

NIH Director's Blog: Drug Development

OCTOBER 30, 2018

Now comes word of another absolutely incredible use of cryo-EM: determining with great ease and exquisite precision the structure of the smaller organic chemical compounds, or “small molecules,” that play such key roles in biological exploration and drug development. Also analyzed were eight less-familiar small molecules.

Small Molecule 52

Small Molecule Science Drug Development Organic Chemistry 52