Drug Hunter, Palo Alto, CA (2025)

10/22/2025

Beyond Retigabine: Can Next-Generation Kv7.2/3 Activators Deliver in Epilepsy? | https://drughunters.com/4719YtQ

Kv7.2/3 activators delivered proof of mechanism, and now the real test is underway. Retigabine showed that boosting the M-current can reduce seizures, but long-term safety challenges and treatment burden stalled the molecule. This article reviews why Kv7 matters in epilepsy, what’s different now, and where the evidence needs to converge to support routine clinical use. We cover azetukalner, opakalim, and other emerging molecules in the re-envigorated KV7.2/3 activator landscape.

Read it on Drug Hunter: https://drughunters.com/4719YtQ

10/20/2025

FDA Decision Nears for Tolebrutinib, a Brain-Penetrant Covalent BTKi for Non-Relapsing Secondary-Progressive Multiple Sclerosis | https://drughunters.com/4o3TS8S

Tolebrutinib is Principia Biopharma/Sanofi's oral, brain-penetrant, covalent BTK inhibitor under FDA review for non-relapsing SPMS (nrSPMS).

After Ph. 1 supported CNS pe*******on, US Ph. 3 trials were briefly placed on partial clinical hold in 2022 due to liver-injury cases; enrollment later resumed under amended protocols with stricter early monitoring of liver function.

In the Ph. 3 HERCULES trials, 60 mg QD reduced the risk of 6-month confirmed disability progression by 31% vs placebo, supporting an NDA that received Priority Review with a PDUFA date of Dec 28, 2025.

Read it on Drug Hunter: https://drughunters.com/4o3TS8S

10/20/2025

Patents are central to the intellectual property strategies that support small molecule drug discovery and development.

In this Flash Talk, Alex Berne and Lucas Watkins, registered patent attorneys at Foley Hoag LLP, will discuss the key fundamentals of patenting small molecule drugs and strategies for building a strong intellectual property portfolio.

They will highlight the importance of patents in drug development, with particular emphasis on the roles of chemical genus and compound claims. Alex and Lucas will also provide guidance on the optimal timing for patent filings, balancing the advantages of generating additional experimental data and securing later expiration dates against the risks associated with delays, including potential public disclosure before filing.

Through real-world case studies, they will walk through the key legal requirements for patentability and explain how to evaluate novelty and nonobviousness relative to prior art.

Sign up now to learn more about state-of-the-art patenting strategies: https://drughunters.com/48EALNO

10/17/2025

TYRA-200: A Next-Generation, Covalent FGFR1/2/3 Inhibitor with Broad Activity Against Resistance Mutations | https://drughunters.com/4nlHkIU

Tyra Biosciences’ TYRA-200 is an oral, covalent FGFR1/2/3-selective inhibitor, that avoids FGFR4 and remarkably retains potency across all common FGFR2 resistance mutations.

FGFR2 is implicated in a number of cancers, and treatment resistance rapidly arises due to mutations that prevent first-generation FGFR inhibitor binding.

Tyra Biosciences has dosed the first patient in its Ph. 1 study in advanced and metastatic cholangiocarcinoma. The structure of TYRA-200 was disclosed at the ACS Fall 2025 First Time Disclosures session.

Read the full case study on Drug Hunter: https://drughunters.com/4nlHkIU

10/17/2025

Finding the right content on Drug Hunter just got easier.

We’ve expanded and updated our article tagging with an expanded set of categories so you can filter and search with more precision. Now you can explore insights by:

-Therapeutic area
- Strategy
- Function
- Product Profile
- Target Class
- Binding
- Article Type
- Record Type
- Review Area
- Modality

Whether you’re looking for examples of a specific modality, benchmarking against product profiles, or diving deep into a therapeutic area, you’ll now get to the right resource faster.

Explore the new categories here: https://drughunters.com/4nZfiE6

10/16/2025

Rilzabrutinib Notches the First US Non-Oncology BTK Inhibitor Approval | https://drughunters.com/43hCbdr

Rilzabrutinib (Wayrilz®) is an oral, reversible-covalent BTK inhibitor approved by the US FDA for treatment of persistent/chronic ITP (immune thrombocytopenia) after prior therapy.

It carries a cyanoacrylamide warhead that reversibly engages Cys481, a non-catalytic cysteine near the ATP site.

Approval was based on the randomized Ph. 3 LUNA-3 clinical trial, which met its primary endpoint of durable platelet response at 400 mg PO BID.

Rilzabrutinib is the first BTK inhibitor approved for a non-oncology indication and the first reversible-covalent BTKi to reach approval.

Read more: https://drughunters.com/43hCbdr

10/15/2025

The second of a two-part review on CDK4/6 inhibitors focuses on the approved molecules that transformed the treatment of HR+/HER2- breast cancer. Palbociclib (Pfizer), ribociclib (Novartis) and abemaciclib (Eli Lilly) have shown a significant extension in progression-free survival when combined with endocrine therapy.

Though all three share a common ATP-competitive binding motif, their divergent chemotypes lead to differences in selectivity and tolerability.
- palbociclib was the first CDK4/6 inhibitor approved and was optimized for CDK4/6 selectivity
- ribociclib achieved >10,000 fold selectivity over other CDKs
- abemaciclib’s distinct benzimidazole core drove broader CDK activity and supported continuous dosing
- differences in CDK selectivity are believed to explain divergent toxicities for palbociclib/ribociclib (neurtopenia) and abemaciclib (diarrhea and fatigue)

Resistance mechanisms involving RB1 loss or CDK2 activation lead the way for the next generation of innovation including CDK4 selective inhibitors like atirmociclib (Pfizer) and CDK2 selective inhibitors like BLU-222 (Blueprint Medicine).

Read more: https://drughunters.com/4okfmhj

10/14/2025

YCT-529: A Selective RAR-α Antagonist Paving the Way for a Non-Hormonal Approach to the First Oral Male Contraceptive | https://drughunters.com/3W22ZdV

YCT-529 is an oral, selective RAR-α antagonist in development as a non-hormonal male contraceptive.

In vivo, once-daily dosing suppressed spermatogenesis within weeks, and fertility returned after the treatment was stopped. In a Ph. 1 single-ascending-dose study, YCT-529 was well tolerated with no meaningful hormone changes, supporting a repeat-dose Ph. 1b/2a study now underway and expected to read out in 2026.

Discovered at the University of Minnesota and developed by YourChoice Therapeutics, YCT-529 highlights the impact of academic–industry partnerships. If trials confirm safety and contraceptive efficacy, it could help address a major unmet need in reproductive health and autonomy.

Read more: https://drughunters.com/3W22ZdV

10/14/2025

Drug Hunter’s members are scientists working on some of the toughest challenges in drug discovery. Hearing how they use Drug Hunter in their research is one of the most rewarding parts of what we do.

These stories remind us why we’re here: to save scientists time, bring forward the most relevant findings, and help drive research forward.

Thank you to our members for sharing your experiences. We’re proud to be part of your discovery journey.

Here are a few highlights from our recent member survey:

10/13/2025

More than 85% of human proteins are still considered undruggable because they lack known or well-defined binding pockets that can be effectively targeted by small molecules.

In this Flash Talk, Daniel Nomura, Professor of Chemical Biology and Molecular Therapeutics, will present his group’s recent efforts applying chemoproteomic approaches to identify and pharmacologically target novel “ligandable hotspots” within disease-relevant proteins.

Daniel will also highlight how chemoproteomic platforms have expanded the scope of emerging therapeutic modalities, including targeted protein degradation and proteolysis-targeting chimeras, through the discovery of several new covalent E3 ligase recruiters.

Sign up now to learn how these cutting-edge technologies are poised to become a mainstay in the development of next-generation therapeutics: https://drughunters.com/4o6i2jb

10/13/2025

In this Flash Talk, Peter Skewes-Cox presented recent AI-driven advances in high-content screening that are accelerating drug discovery by augmenting and even replacing traditional workflows.

Peter emphasized that while HCS once depended on manual processing, deep learning methods now allow for a higher degree of automation. Inspired by innovations in natural image classification and autonomous driving, AI methods have significantly advanced cellular image interpretation.

Generative AI approaches, including in silico labeling and profile-conditioned diffusion, further extend these capabilities. ISL predicts fluorescent images from cost-effective brightfield microscopy to support large-scale phenotypic similarity searches, while PCD generates synthetic microscopy images from bioactivity profiles, significantly improving hit identification without wet-lab experiments.

To understand how AI has changed the game in high-content screening, watch the full Flash Talk now: https://drughunters.com/42BgbtX

10/11/2025

Dordaviprone Is the First FDA-Approved Therapy for H3K27M-Mutant Diffuse Midline Glioma | https://drughunters.com/4h1HweC

Dordaviprone received FDA accelerated approval for the treatment of DMG (diffuse midline glioma) harboring the H3(K27M) mutation in patients ≥1 year old with progressive disease after prior therapy.

A first-in-class, oral, brain-penetrant imipridone, dordaviprone combines mitochondrial ClpP hyperactivation with D2R antagonism, dual mechanisms implicated in antitumor activity across glioma models.

It is the first FDA-approved systemic therapy specifically for H3(K27M)–mutant DMG—a disease that primarily affects children and young adults—and the first imipridone from the Chimerix/Jazz Pharma partnership to reach approval.

Read more: https://drughunters.com/4h1HweC

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