Six science picks span hit-finding platforms to a MurB PET probe; six business items include Kodiak's Eylea-rival trial win, Mirum's third FOP approval, a Merck/Daiichi ADC withdrawal, a Merck KRAS licensing deal, AbbVie's Parkinson's nod, and a Maruho-BMS Japan tie-up.
2026-09-27 · ⚗️Ligand-detected NMR screening/hit-triage platform (methodology/platform paper, not target-specific) · Journal of Medicinal Chemistry (ACS)
- An automated, high-throughput ligand-detected NMR method targets hit triage in medicinal chemistry screening campaigns.
- The approach is framed as enabling rapid, qualitative binding assessment of screening hits at scale.
- Reads as a platform/methodology contribution focused on throughput and workflow automation rather than a single target or chemical series.
💡 PointsNMR gives you binding mode, not just 'yes it binds' — that's the filter SPR and TSA can't offer, especially for the promiscuous frequent-hitters that eat up your week. If the automation actually holds up at HTS volumes, this slots in as a fast confidence check before compounds go into a co-crystal queue, not a replacement for it.
Automated High-Throughput Ligand-Detected NMR for Medicinal Chemistry Hit Triage and Binding Assessment ↗
2026-09-27 · ⚗️Cruzain / Cathepsin L — covalent cysteine protease inhibitors · ChemMedChem (Wiley)
- Uses relative binding free energy (FEP-type alchemical) calculations to compare warhead-bearing covalent inhibitors across two related cysteine proteases.
- Cruzain, the key protease of Trypanosoma cruzi (Chagas disease), and human cathepsin L, its close homolog, are modeled in parallel.
- Comparison highlights selectivity for the parasitic target versus off-target reactivity with the human enzyme, guiding optimization.
💡 PointsFEP on a reactive warhead is still shakier than on reversible binders — parameterizing the covalent bond is where these methods quietly break. Still, cat L cross-reactivity has sunk more cruzain leads than weak potency ever did, so a validated ΔΔG ranking that flags off-target binders before synthesis is real triage value — worth having when neglected-disease budgets don't cover redundant chemistry.
Assessment of the Binding Affinity of Covalent Inhibitors of Cruzain and Cathepsin L Using Relative Binding Free Energy ↗
2026-09-27 · ⚗️Transthyretin (TTR) stabilizer, CNS-penetrant small molecule · Journal of Medicinal Chemistry (ACS)
- A new series of neutral, heterocyclic-linker-containing transthyretin (TTR) stabilizers is designed for improved brain and cerebrospinal fluid (CSF) penetration.
- Aims to address CNS/leptomeningeal manifestations of hereditary ATTR amyloidosis, where existing acidic stabilizers such as tafamidis show limited CNS exposure.
- Heterocyclic linker modifications reduced compound acidity relative to earlier chemotypes while reportedly preserving TTR tetramer-stabilizing potency and selectivity in vitro.
💡 PointsFinally—someone attacking the acidic-pharmacophore/P-gp efflux tradeoff head-on instead of just tolerating tafamidis's CNS blind spot. Ditching the carboxylic acid for heterocyclic linkers while holding onto tetramer-stabilizing potency is the hard part of this SAR, not the easy part. If CSF exposure holds up in vivo, leptomeningeal ATTR patients finally get a real option instead of an afterthought.
Discovery of Neutral and Cerebrospinal Fluid Penetrant Transthyretin (TTR) Stabilizers with Heterocyclic Linkers ↗
2026-09-27 · ⚗️Methodology/platform paper on direct-to-biology (D2B) screening: compounds synthesized at nanoscale and crude, unpurified reaction mixtures assayed directly, skipping isolation/purification to speed up hit identification. · Journal of Medicinal Chemistry (ACS)
- A direct-to-biology (D2B) platform synthesizes candidate compounds at small scale and evaluates the crude reaction mixtures directly in biological assays, bypassing conventional purification.
- The approach couples miniaturized, automation-compatible chemistry with rapid biological readout to shorten the design-make-test cycle typical of early hit-finding and library exploration.
- Positioned within a broader wave of D2B methodology in medicinal chemistry, applicable to accelerating hit identification across diverse chemotypes.
💡 PointsSkipping purification is the real win—cuts days off the DMT cycle when you're triaging hundreds of analogs. But I want hard numbers on false-positive rates from residual catalyst/byproducts before trusting crude-mixture hits blind; great for rapid SAR triage, not for anything feeding a confirmatory dose-response.
Direct-To-Biology Platform Enabled Drug Discovery ↗
2026-09-27 · ⚗️LSD1 (KDM1A) inhibition · Journal of Medicinal Chemistry (ACS)
- Perspective-style article proposing that pharmacological inhibition of the epigenetic enzyme LSD1 (KDM1A) can modulate cellular sensitivity to nucleoside analogue therapeutics.
- Synthesizes evidence across myeloid malignancies and viral infections, two disease areas where nucleoside analogues are already established treatments.
- Argues LSD1-driven chromatin and transcriptional changes may underlie altered drug response, positioning LSD1 inhibitors as potential combination partners to enhance nucleoside analogue efficacy across both fields.
💡 PointsWhat grabs me is that clinical-stage LSD1 chemotypes already exist (bomedemstat, seclidemstat, and friends) — if the chromatin argument holds up, repurposing into combo trials is cheap and fast. But this is a Perspective stitching two literatures together, not new data; before I'd trust a DDI-manageable combo across both AML and antivirals, I want real mechanistic proof that LSD1 inhibition actually changes nucleoside analogue uptake/incorporation, not just correlation.
Targeting LSD1 Modulates Therapeutic Responses to Nucleoside Analogues: From Myeloid Malignancies to Viral Infections ↗
2026-09-27 · ⚗️MurB (bacterial cell-wall/peptidoglycan biosynthesis enzyme) — PET imaging probe · Journal of Medicinal Chemistry (ACS)
- Iron-binding chemistry anchors a new bacteria-targeted imaging probe engaging MurB, an enzyme unique to bacterial peptidoglycan (cell-wall) biosynthesis, for radiolabeling.
- The probe is proposed as a platform for PET (positron emission tomography), aiming to visualize actual bacterial infection sites in vivo rather than relying on nonspecific inflammation markers.
- By targeting a pathway absent in human cells, the approach could help clinicians distinguish genuine bacterial infection from sterile inflammation, addressing a longstanding gap in infectious-disease imaging.
💡 PointsMurB being absent in human cells is about as clean a selectivity handle as probe chemistry gets, aimed at a real gap — FDG-PET can't tell infection from sterile inflammation. The iron-chelating warhead is a neat trick too: swap in a radiometal and the labeling chemistry comes free. Makes you wonder if that MurB-binding core doubles as an antibacterial lead.
Leveraging the Iron-Probe-MurB Interaction: An Enhanced Platform for PET Imaging of Bacterial Infections ↗
2026-09-28 · 🏢trial result · STAT News · AbbVie
- FDA approved AbbVie's Juvmo (tavapadon), a once-daily oral pill for Parkinson's disease, usable alone early on or alongside levodopa for motor fluctuations.
- It's the first selective D1/D5 dopamine receptor partial agonist approved for Parkinson's, a mechanism distinct from older D2/D3 agonists, aimed at controlling motor symptoms with fewer impulse-control or sleep-attack risks.
- AbbVie gained tavapadon via its 2023 Cerevel Therapeutics acquisition; US launch is planned October 2026.
💡 PointsThis is AbbVie's first tangible payoff from the $8.7B Cerevel bet — proof the deal wasn't just pipeline padding. But novelty alone won't move share: Parkinson's prescribing is sticky, generics dominate, and neurologists switch stable patients reluctantly. The cleaner side-effect profile is a real wedge, yet formulary inertia will decide if it's more than a niche add-on.
AbbVie wins FDA nod for Parkinson's pill ↗
2026-09-28 · 🏢trial result · Endpoints News · Kodiak Sciences
- Kodiak Sciences' Phase 3 DAYBREAK trial met primary endpoints for both Zenkuda (tarcocimab tedromer) and tabirafusp-ted (KSI-501) in wet age-related macular degeneration, with vision gains comparable to Regeneron's Eylea (aflibercept).
- The majority of Zenkuda patients achieved a six-month dosing interval, versus Eylea's standard eight-week schedule.
- Kodiak plans to file a Biologics License Application with the FDA in Q4 2026.
💡 PointsMatching Eylea's efficacy is table stakes; the six-month interval is the real lever, potentially beating Eylea HD's and Vabysmo's quarterly dosing on the metric that drives adherence — treatment burden. That strengthens Kodiak's BLA package and partnership leverage more than raw efficacy parity would. Risk: without a durability edge, six-month dosing could compress once real-world data arrives.
Kodiak's stock soars as it clinches crucial Phase 3 win for Eylea competitor ↗
2026-09-28 · 🏢partnership · Endpoints News · Merck & Co. / SciBrunch Therapeutics
- Merck & Co. entered an exclusive global license agreement with Shanghai-based SciBrunch Therapeutics for SPR2015, an investigational oral KRAS G12D molecular-glue inhibitor.
- SciBrunch will receive $400 million upfront, with total deal value up to $2.13 billion including milestone payments.
- The deal reflects a growing trend of U.S. pharma companies in-licensing China-originated oncology assets.
💡 PointsThis plugs Merck's biggest KRAS gap: everyone's crowded into G12C, but G12D — more common in pancreatic and colorectal cancer — has stayed stubbornly undrugged with covalent chemistry. A molecular-glue approach, if it works, sidesteps that entirely. The modest 19% upfront-to-total ratio signals early-stage derisking, not a validated asset — expect Western rivals to scramble for the remaining China-origin G12D candidates.
Merck licenses a KRAS G12D inhibitor for $400M upfront ↗
2026-09-25 · 🏢partnership · AnswersNews · Maruho / Bristol Myers Squibb
- Maruho and Bristol Myers Squibb (BMS) signed a Japan sales partnership for Sotyktu (deucravacitinib), BMS's oral TYK2 inhibitor, starting October 1, 2026.
- Maruho will handle domestic sales and distribution, promoting the drug in dermatology and rheumatology, while BMS continues promotion in rheumatology.
- Sotyktu is approved for plaque, pustular and erythrodermic psoriasis, with a psoriatic arthritis indication added in May 2026.
💡 PointsBMS ceding Japan commercial lead to Maruho is a tacit admission that dermatologist relationships beat global scale here — the classic foreign-innovator/domestic-specialist access play. Adding rheumatology promotion right after the May PsA nod signals urgency to outrun oral JAK rivals before positioning hardens. For Maruho, it's low-risk topline padding that fits its derm book without R&D exposure.
マルホ、ブリストルのTYK2阻害薬「ソーティクツ」の国内販売で提携 ↗
2026-09-25 · 🏢discontinuation · Endpoints News · Merck & Co. / Daiichi Sankyo
- Merck & Co. and Daiichi Sankyo voluntarily withdrew their FDA BLA for ifinatamab deruxtecan, a B7-H3-targeted ADC, in previously treated ES-SCLC.
- FDA feedback indicated Phase 2 data didn't support accelerated approval, marking the alliance's second pullback for the drug after an earlier lung-toxicity-related clinical hold.
- The companies continue the Phase 3 IDeate-Lung02 confirmatory trial and other Phase 3 studies in prostate and esophageal cancer.
💡 PointsA second stumble for the same molecule is a real signal, but it's about ifinatamab deruxtecan's timeline, not the Merck-Daiichi deal's overall health — this alliance is bigger than one BLA. Withdrawing rather than fighting for a contested approval is the disciplined move, protecting IDeate-Lung02's confirmatory data package. But every added year gives rival B7-H3 ADC programs room to catch up.
Merck, Daiichi scrap FDA application for B7-H3 ADC in lung cancer ↗
2026-09-25 · 🏢regulatory approval · FiercePharma · Mirum Pharmaceuticals
- The FDA approved Mirum Pharmaceuticals' Atebrioz (zilurgisertib), an oral ALK2 inhibitor licensed from Incyte, for patients 12 and older with fibrodysplasia ossificans progressiva (FOP), an ultra-rare bone disorder.
- It's the third approved FOP therapy, after Sohonos (palovarotene) and Regeneron's Pasatru (garetosmab), sharpening rivalry between Mirum and Regeneron.
- In its pivotal trial, Atebrioz notably reduced new heterotopic ossification (abnormal bone growth) versus placebo.
💡 PointsThree mechanisms chasing one ultra-rare population signals a share fight, not market expansion — FOP's patient pool won't stretch to reward a late third entrant on volume alone. Oral dosing is Mirum's real differentiator against Regeneron's IV antibody, and the Incyte in-license shows Mirum building a rare-bone-disease franchise by acquiring assets rather than discovering them.
Mirum bags FDA approval for ultra-rare bone lesion disorder, heating up rivalry with Regeneron ↗