Drug Hunter, Palo Alto, CA (2025)

12/01/2025

Next-Generation Oral SERD Giredestrant (GDC-9545) Shows Adjuvant Benefit in Early Phase 3 Data | https://drughunters.com/444FiWK

Giredestrant (GDC-9545) is Genentech's next-generation oral SERD (selective estrogen receptor degrader) and full ER antagonist in Ph. 3 development for ER+/HER2- breast cancer.

The compound emerged from an SAR campaign profiling over 4,000 compounds and showed robust single-agent activity with improved efficacy in combination with a CDK4/6 inhibitor. Asymptomatic, dose-dependent bradycardia at higher doses motivated the selection of a lower once-daily oral dose—a finding that mirrors low-grade bradycardia signals seen with other oral SERDs, including AstraZeneca’s camizestrant.

Early data from the ongoing lidERA trial in early ER+/HER2- breast cancer also support its potential as an adjuvant therapy.

With elacestrant and, more recently, Lilly’s imlunestrant already approved as oral nonsteroidal SERDs for ESR1-mutated advanced disease, giredestrant is now positioned to test whether this class can move beyond late-line rescue into both post-CDK4/6 metastatic and adjuvant early-stage settings.

Read it on Drug Hunter: https://drughunters.com/444FiWK

11/26/2025

Surface Plasmon Resonance: Enabling Insights into Kinetics and Mechanism | https://drughunters.com/3XRbeu1

SPR has evolved into a core technology for drug discovery, delivering real-time, label-free kinetic and mechanistic insight. This brief article provides a high-level overview of how SPR works and how it is evolving to provide even more value to scientists. It also highlights use cases for SPR including applications in antibody discovery, fragment-based screening, and understanding the binding kinetics of heterobifunctional molecules.

Read it on Drug Hunter: https://drughunters.com/3XRbeu1

11/25/2025

Paltusotine: The First Oral Nonpeptide SST2 Agonist for Acromegaly | https://drughunters.com/4ip28OE

In September 2025, paltusotine (Palsonify®) became the first nonpeptide oral therapy to gain FDA approval for the treatment of acromegaly.

This rare disease has historically been treated with injectable peptide agonists of SST2, contributing to treatment burden and adherence challenges.

Paltusotine, a small molecule agonist of SST2, demonstrated an excellent safety profile and robust efficacy in Ph. 3 trials, supporting its use as an oral alternative to injectable standard-of-care therapies. In addition to its recent approval in acromegaly, paltusotine has entered Ph. 3 trials for carcinoid syndrome in patients with NETs.

This case study reviews the current therapies for acromegaly, the preclinical and clinical data that supported paltusotine’s approval, and the potential of this compound to benefit a broader population with carcinoid syndrome.

Read it on Drug Hunter: https://drughunters.com/4ip28OE

11/24/2025

TCIPs: Heterobifunctional Compounds for Gene Activation | https://drughunters.com/4pOlkYP

TCIPs (transcriptional/epigenetic chemical inducers of proximity) are a fascinating new class of heterobifunctional recruiters developed by Nathanael Gray and Gerald Crabtree at Stanford University. Their seminal publications showcase incredibly selective small molecules with potent BCL6-addicted cell-killing effects via a CDK9 recruiter tethered to a BCL6 targeting moiety. This ternary complex re-activates apopotic gene pathways suppressed by BCL6 and achieves a long-standing goal in cancer research: overcoming BCL6 oncogenesis.

Check out our modality brief on this new approach and learn about their company, Shenandoah Therapeutics, that just emerged from stealth this summer to pursue clinical applications.

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

11/24/2025

Year-End Special Flash Talk: 2024 Molecules of the Year: Scientific Highlights
https://drughunters.com/4oTpr5t
Thursday, December 11th, 2025
8 AM PT | 11 AM ET | 5 PM CET

While the biopharma industry faces many challenges, there has never been a more exciting moment for small molecule drug discovery.

In this Year-End Special Flash Talk, Dennis Koester will highlight the major trends and scientific breakthroughs emerging from the 2024 Molecules of the Year candidates. Dennis will explore how small molecules and macrocyclic peptides are now competing on targets once dominated by biologics, showcase transformative advances in pain therapeutics, and examine how modern tools and strategies are enabling researchers to drug previously “undruggable” proteins.

Dennis will also share cutting-edge discoveries in induced proximity, from monovalent approaches to bifunctional degraders, illustrating how new modalities and deeper mechanistic insights continue to expand what is possible in small molecule research.

Secure your spot here: https://drughunters.com/4oTpr5t

11/21/2025

October 2025 Patent Highlights | https://drughunters.com/4o6JSLj

Every month at Drug Hunter, our team screens thousands of new patent filings to surface a small subset that we believe might really move the needle in drug discovery. Our October 2025 patent highlights are now live.

This month, we cover: Amphista's FBXO22-recruiting TEAD degraders, Septerna's small molecule PTH1R agonists, Kyorin’s first post-Novartis-deal MRGPRX2 antagonists in the mast cell/allergy space, and Rigel’s dual IRAK1/4 inhibitor chemotype designed to deepen TLR and IL-1R pathway suppression in inflammatory diseases.

If you work on challenging targets, targeted protein degradation, or innate immune signaling, this one is worth a read.

Read it on Drug Hunter: https://drughunters.com/4o6JSLj

11/21/2025

📣 Reminder
Targeting NLRP3: DFV890 and Beyond
https://drughunters.com/3JLsxJO
Thursday, December 4th, 2025
8 AM PT | 11 AM ET | 5 PM CET

Join us for a Flash Talk with Angela Mackay on targeting NLRP3 for peripheral and CNS indications.

Among other NLRP3-targeting campaigns, Angela will share the discovery story behind DFV890, the first and only sulfonimidamide-containing small molecule in clinical development, now progressing through multiple Phase 2 trials across several indications.

Save your spot here: https://drughunters.com/3JLsxJO

11/20/2025

Molecules of the Month – October 2025 | https://drughunters.com/48qIXR2

Drug Hunter’s October picks spotlight pritelivir, Aicuris’ potential first-in-class HSV helicase–primase inhibitor with a registrational Ph. 3 win in refractory immunocompromised patients; ML-007, a dual M1/M4 muscarinic agonist that outperforms xanomeline in preclinical psychosis models; and [18F]ACI-19626, a TDP-43–selective PET tracer that could finally enable in vivo imaging of TDP-43 proteinopathies.

Rounding out the list:
– lanifibranor — Inventiva’s oral pan-PPAR agonist delivering histologic and cardiometabolic benefits in MASH
– xevinapant — an oral IAP antagonist whose CRT combo failure in SCCHN highlights how immunosuppressive TME effects can undermine promising Ph. 2 data
– RMC-5552 — Revolution Medicines’ bi-steric mTORC1-selective inhibitor that reactivates 4EBP1, shows ctDNA pathway clearance, and mitigates mTORC2-driven hyperglycemia
– Opitor-0 — a specific OPA1 inhibitor that remodels mitochondrial cristae to overcome venetoclax resistance in AML and creates new metabolic vulnerabilities
– TTI-101 — Tvardi’s oral STAT3 inhibitor, whose negative Ph. 2 IPF readout offers a reality check on “undruggable” STAT3 in fibrotic lung disease
– zilurgisertib — a highly selective, oral ALK2 (ACVR1) inhibitor that fully suppresses heterotopic ossification in FOP models and is now in clinical trials
– compound 23 — a macrocyclic STK10 inhibitor that exploits a unique back-pocket binding mode to achieve nanomolar cellular potency and exceptional kinome selectivity

Read the full article to explore the molecules that made our October 2025 list: https://drughunters.com/48qIXR2

11/19/2025

Dual Neurokinin Receptor Antagonist Elinzanetant Approved for Menopausal Vasomotor Symptoms | https://drughunters.com/49nF00y

Elinzanetant is a dual NK1R/NK3R antagonist approved in October 2025 for the treatment of moderate to severe VMS due to menopause.

Originally developed as a potential therapy for depression, addiction, and schizophrenia, elinzanetant was later repurposed for menopausal VMS once the role of NK3 receptor signalling in hot flashes was appreciated.

In a suite of Ph. 3 trials, elinzanetant reduced the frequency and severity of hot flashes and improved sleep and overall quality of life. In an indirect meta-analysis of randomized trials versus placebo, elinzanetant appeared to outperform the selective NK3 receptor antagonist fezolinetant with larger effects on VMS symptoms and sleep quality.

Check out the full case study on Drug Hunter: https://drughunters.com/49nF00y

11/19/2025

Drug Discovery Course Navigation Webinar | https://drughunters.com/3X0mnZh
Tuesday, December 9th, 2025
8 AM PT | 11 AM ET | 5 PM CET

Be among the first to explore our Drug Discovery Course, launching in January. Join us live December 9th for an exclusive preview–your chance to explore the course interface, understand the syllabus and cadence, and engage our team with your questions. Whether you’re considering 'enrolling' or curious to learn what’s ahead, we invite you to be part of this sneak peek!

Register here: https://drughunters.com/3X0mnZh

11/18/2025

Daraxonrasib (RMC-6236): A Ground-Breaking, pan-RAS Mutant Tri-complex Glue Inhibitor Receives a National Priority Voucher | https://drughunters.com/47YH3FT

Daraxonrasib (RMC-6236) in a non-covalent pan-RAS(ON) inhibitor, potently inhibiting all isoforms including oncogenic KRAS, NRAS, and HRAS mutants as well as wild-type RAS.

The compound exerts its action via a “tri-complex” mechanism, gluing RAS to the ubiquitously expressed chaperone protein, cyclophilin A. Clinical data has shown striking regressions in tumors driven by previously “undruggable” RAS mutations.

Daraxonrasib received Breakthrough Therapy and Orphan Drug designations, and was in the inaugural group of programs to receive the FDA’s new National Priority Vouchers, guaranteeing an expedited 1-2 month review upon NDA submission for pancreatic cancer.

Read it on Drug Hunter: https://drughunters.com/47YH3FT

11/18/2025

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