Drug Hunter

OP-3136, Olema’s KAT6 Inhibitor Shows Promise in Preclinical Models of Breast Cancer | https://lnkd.in/e6xgb6QV OP-3136, the KAT6A-selective inhibitor currently in Ph. 1/2 trials for advanced breast cancer, was disclosed by Olema Pharmaceuticals’ David Myles at the ACS Spring 2026 First Time Disclosures. KAT6 has emerged as a target of interest in the oncology field due to its role as an “epigenetic writer” that enables upregulation of numerous oncogenic drivers, including myc. OP-3136 utilizes an acylsulfonamide to mimic the pyrophosphonate moiety of KAT6’s natural substrate, acetyl coenzyme A. OP-3136 is currently being evaluated in the clinic in combination with SERDs including Olema’s own palazestrant (OP-1250), with preliminary data expected later this year.

Chantix: Targeting Nicotine Addiction with Partial α4β2 Agonism | https://lnkd.in/eNGYe2X4 Varenicline (Chantix®) remains a notable case study in drug discovery and development for nicotine addiction. Approved in 2006 for smoking cessation, it emerged at a time when treatment options were still limited, and the public health burden of tobacco use remained enormous. Its story goes well beyond clinical efficacy. Chantix shows how receptor pharmacology, medicinal chemistry, pivotal clinical trials, and post-approval safety and quality challenges can all shape the life cycle of a drug. In this Drug Hunter article, we trace the path from cytisine-inspired lead discovery to varenicline’s clinical success, turbulent post-approval history, and the return of cytisine as cytisinicline.

In this Flash Talk, Peter Tummino presented preclinical data supporting the selective inhibition of SIK2 for the treatment of chronic inflammatory diseases such as ulcerative colitis. After outlining the importance of selective SIK2 inhibition and delineating potential on-target effects related to inhibition of SIK1 and SIK3, Peter presented a suite of data to support the pursuit of SIK2 as a viable target. These data show that the SIK2 inhibitor NTX-147 suppresses pro-inflammatory cytokines like TNFα and IL-23, while promoting IL-10 production, a key activator of tissue repair. This pharmacological profile differentiates SIK2 inhibitors from SIK3 inhibitors as well as JAK inhibitors such as upadacitinib. This effect was also observed in in vivo mouse models, where a reduction in proinflammatory cytokines and a concomitant increase in IL-10 was observed, further supporting the therapeutic hypothesis. In addition to the PD data presented, robust efficacy was observed in Anti-CD40 and DSS colitis models with reduced disease activity and increased gut barrier integrity. Furthermore, gene expression analysis from these models indicate an upregulation of tissue repair pathways and downregulation of inflammatory pathways. Peter concluded by sharing a summary of early data supporting the application of SIK2 inhibition for the treatment of rheumatoid arthritis. If you are interested in the pharmacology of selective SIK2 inhibition and would like to learn more, watch the full Flash Talk on our YouTube channel: https://lnkd.in/druTWdxW

March 2026 Patent Highlights | https://lnkd.in/efKYJG-x This month’s selections cover notable new IP disclosures across cardiovascular, metabolic, CNS, and oncology targets, including: • NPR1 activators for heart failure • GOAT inhibitors for impulsivity-linked addiction • CRFR2 agonists for lean-mass-preserving weight loss • ABHD6 inhibition as a CNS-oriented endocannabinoid strategy • WDR5 inhibitors for transcriptionally driven cancers As always, we’ve distilled the key biology, chemistry, and translational context from these disclosures to help you stay current on the IP that matters most.

Our analysis of 2025 global small molecule drug approvals is now open access. Here, we examine first-time approvals across Europe’s EMA, China’s NMPA, and Japan’s PMDA, highlighting the key trends shaping drug discovery worldwide. Across these agencies: - 38 small molecules were approved - Oncology dominated, representing a broad range of targets and tumor types - Infectious disease remained a major focus, including HCV, influenza A/B, and COVID-19 We also explore the broader therapeutic areas and mechanisms driving innovation across the global landscape. Read the open access article here: https://lnkd.in/ep4kuAnM

Molecules of the Month – March 2026 | https://lnkd.in/eUwUK8RE Drug Hunter’s March picks spotlight relacorilant, Corcept Therapeutics' newly approved selective glucocorticoid receptor antagonist that establishes cortisol modulation as a new mechanism in platinum-resistant ovarian cancer; cleminorexton, Eli Lilly and Company/Centessa Pharmaceuticals's oral orexin receptor 2 agonist emerging as a potential best-in-class therapy for narcolepsy and idiopathic hypersomnia; and alrizomadlin, an oral MDM2 inhibitor showing encouraging activity in TP53 wild-type salivary gland cancers. Rounding out the list: – compound 12 — Merck's CNS-penetrant macrocyclic LRRK2 inhibitor that showcases how macrocyclization can help solve the potency/selectivity/brain-penetration puzzle in Parkinson’s drug discovery – AP306 (EOS-789) — a first-in-class oral pan-phosphate transporter inhibitor aiming to lower serum phosphate in dialysis patients by blocking GI phosphate uptake rather than binding phosphate in the gut – TAS1440 — an LSD1 inhibitor that dismantles the INSM1–LSD1 transcriptional axis in neuroendocrine SCLC and reprograms tumor cell state – darlifarnib — Kura Oncology, Inc.'s next-generation farnesyl transferase inhibitor that may help resensitize renal tumors to VEGFR TKIs by suppressing adaptive RHEB–mTORC1 signaling – ARD-101 — Aardvark Therapeutics' gut-restricted TAS2R agonist, a differentiated oral metabolic program now paused after dose-related cardiac observations – compound 23 — Pfizer's brain-penetrant GPR61 inverse agonist that opens a new angle on metabolic disease biology through an induced intracellular allosteric pocket – compound 3 — Daiichi Sankyo Japan's colon-targeted O-glucuronide prodrug of an E. coli biofilm inhibitor that boosts lower-GI delivery and outperforms the parent agent in a colitis model Read the full article to explore the molecules that made our March 2026 list.

Dual CDK4/2 Inhibitor from Regor, Acquired by Genentech, Demonstrates Positive Preliminary Clinical Data | https://lnkd.in/ejvCPFai Dr. Wenge Zhong of Regor Therapeutics Group presented the discovery story of GDC-4198, an oral CDK4/2 inhibitor currently in Ph. 1/2 trials for advanced solid tumors. Discovered at Regor and later acquired by Genentech, this molecule combines the impressive CDK4 potency of compounds like abemaciclib with low nanomolar CDK2 potency and nearly 20-fold selectivity over CDK6 to deliver a differentiated profile. Early clinical data for this compound include single agent efficacy in patients who previously progressed on CDK4/6 therapy.

Liganded Structures | https://lnkd.in/d_nPnGf7 Few areas of drug discovery have been transformed as rapidly as protein structure — reshaped by advances in experimental technology and machine learning over the last decade. In the first lecture of the Protein Structure & Target Pharmacology module, we introduce protein-associated considerations for selecting an expression system and structural assessment method, and discuss some of the applications for HDX-MS, X-ray crystallography, Cryo-EM, and ML models. Due to inherent constraints for all structure characterization technologies, project teams are likely to rely on several complementary approaches in the course of a drug discovery campaign. Understanding the strenghts and limitations of each approach can help project teams prioritize resources and strategically deploy the optimal methods. Happy Learning! 🎓

Alnodesertib (ART0380): a Twist on Sulfoximines for ATR Inhibition | https://lnkd.in/gh_kuChU Alnodesertib, an ATR inhibitor targeting the DDR pathway, is progressing through the clinic, garnering FDA Fast Track designation in ATM-negative metastatic colorectal cancer based on results from the Ph. 1/2a STELLA trial. Discovered at MD Anderson’s IACS and under development by Artios, alnodesertib contains an N-linked sulfoximine that was key to optimizing selectivity over other PIKK family members such as PI3K and mTOR. Artios recently raised a $115M series D funding round to continue clinical studies of its DDR portfolio, and efforts continue to add ATR as another tool in the DDR toolbox following the success of PARP inhibitors. However, questions remain about optimal dosing regimen, combination partners, and patient populations in light of narrow TIs observed across the class.

Molecule Search is live – a faster, more connected way to explore data across the industry. We just launched a major upgrade to the Drug Hunter platform — built to help you rapidly act on insights from the rest of the industry. What’s inside: - Rapid, consolidated searches across Drug Hunter Molecules, FDA-Approved Drugs, and Modern Clinical Compounds in parallel  - Structure-searchable disclosures indexed to targets, MoA’s, and therapeutic areas - Structures visualized across chemical space, with filters to refine by relevant molecular properties - Direct links to 3D structures of compounds and targets Fragmented tools and disconnected databases have long been the reality of structure-based research. This upgrade continues to redefine how Drug Hunter helps researchers explore industry-relevant data by bringing everything together in one place. The same trusted data — now more powerful. Explore the update: https://lnkd.in/eBrR-KSx