Chicago—An 8 a.m. start time, 6 p.m. finish, and long walk to a far corner of Chicago’s McCormick Place Convention Center. These things did not deter attendees from the Division of Medicinal Chemistry’s perennially popular first-time disclosures session on Wednesday at the American Chemical Society Fall 2026 meeting (ACS publishes C&EN but is not involved in editorial decisions). A crowd packed into a large meeting room to hear talks about medicinal chemistry campaigns from companies, large and small. Speakers unveiled structures of 13 new drug candidates that were invented to treat a wide range of diseases, including cancer, lupus, and acne.
Presenters discussed an array of approaches to drug discovery and strategies that took years to execute in some cases. Other campaigns, such as that for Pfizer’s glucose-dependent insulinotropic polypeptide receptor antagonist PF-07976016, took only a matter of months.
Session chair H. Rachel Lagiakos of Novartis told C&EN that ACS’s 150th anniversary was a time to reflect “on what a century and a half of scientific excellence enables.” She said in her opening remarks that each of the clinical candidates presented during the session “represents years of persistence, creativity, and problem-solving across our global medicinal chemistry community.”
Candidate: QTX3034
Presenter: Hong Lin, Quanta Therapeutics
Target: KRas (G12D mutation)
Disease: Endometrial cancer, colorectal cancer, and pancreatic ductal adenocarcinoma
Clinical: Phase 1 (NCT06227377)
Related: “Notorious KRAS: Taking Down Cancer Researchers’ Biggest Foe”
Notes: QTX3034’s spirocycle was part of the campaign’s original design. It provides rigidity in an allosteric site on several KRas mutants.
Candidate: AZD3632
Presenter: Gerjan de Bruin, Acerta Pharma/AstraZeneca
Target: Menin
Disease: Acute myeloid leukemia, acute lymphoblastic leukemia
Clinical: Phase 1 (NCT07155226)
Related: “AstraZeneca Snags Stake in Acerta ”
Notes: AZD3632 features a ketone, a motif that is often a liability in drug candidates because it can compromise a compound’s stability. Although the researchers looked into removing the ketone, it proved not to be a problem and instead makes key interactions with the candidate’s target.
Candidate: NVP-KFA115
Presenter: Simone Bonazzi, Novartis
Target: Ikaros family zinc finger 2 (IKZF2 Helios) and Ikaros family zinc finger 4 (IKZF4 Eos)
Disease: Immunomodulation for cancer
Clinical: Phase 1 (NCT05544929)
Related: “Changing Tactics for Targeting Ikaros Proteins in Cancers”
Notes: The trans-cyclohexylamine-ether on NVP-KFA115 arose from a by-product of a carbon-oxygen cross-coupling reaction when the substrate reacted with a copper ligand. The researchers decided to test this by-product for activity, and the results shifted the project in a new direction.
Candidate: SGR-3515
Presenter: Jiashi Wang, Schrödinger
Target: WEE1 G2 checkpoint kinase (Wee1) and myelin transcription factor 1 (Myt1)
Disease: Solid tumors
Clinical: Phase 1 (NCT06463340)
Related: “A Computational Shortcut to Selectivity Creates Precise Kinase Inhibitors”
Notes: The Schrödinger researchers started their virtual screening with 447 million compounds. They attribute SGR-3515’s improved kinase activity to its high sp3 character, which anchors it within its targets.
Candidate: GFH647
Presenter: Tao Jiang, GenFleet Therapeutics
Target: Bruton tyrosine kinase (BTK, wild-type and C481S mutation)
Disease: B-cell malignancies
Clinical: Investigational new drug approval
Related: “To Battle B-Cell Cancers, Drugmakers Are Going Beyond the Covalent Bond”
Notes: GFH647’s deuterated methyl and methoxy groups extended the compound’s metabolic stability as compared with the nondeuterated versions.
Candidate: Iptocigistat (VENT-03)
Presenter: Ramsay Beveridge, Ventus Therapeutics
Target: Cyclic GMP-AMP synthase (cGAS)
Disease: Systemic lupus erythematosus
Clinical: Phase 2a (NCT07260877)
Related: “Ventus Therapeutics Launches to Drug Inflammasomes, cGAS, and More”
Notes: Iptocigistat features a pyrone, which is an unconventional motif in drugs. Beveridge hopes the drug candidate inspires others to use pyrones in their campaigns. “They’re actually better than you think,” he said.
Candidate: PF-07905428
Presenter: Gwenaella Rescourio, Pfizer
Target: Acetyl CoA carboxylase (ACC)
Disease: Acne vulgaris
Clinical: Phase 1 (NCT06671834), discontinued
Related: “These Drug Candidates Excited Researchers 10 Years Ago. What Happened?”
Notes: Rescourio said that one of the key challenges in developing a topical agent such as PF-07905428 was delivering enough of the compound to the site of action—the hair follicle and sebum gland.
Candidate: DA-003
Presenter: Craig Stivala, Deep Apple Therapeutics
Target: Mas-related G protein–coupled receptor family member X2 (MRGPRX2)
Disease: Mast cell–driven inflammatory diseases, such as atopic dermatitis, asthma, and migraine
Clinical: Clinical trial application submitted
Related: “Deep Apple Therapeutics Launches with Small-Molecule Drug Discovery Program”
Notes: Deep Apple began this campaign with a virtual screen that looked at more than 560 million molecules. DA-003’s N-oxide appears to have a significant stabilizing interaction with its target’s N-terminal tail, Stivala said.
Candidate: BLU-808/SAR449028
Presenter: Guangyan Du, Blueprint Medicines/Sanofi
Target: Receptor tyrosine kinase KIT
Disease: Chronic urticaria
Clinical: Phase 2 (NCT06931405)
Related: “Sanofi to Buy Blueprint Medicines”
Notes: The fluorine in BLU-808 proved to be key in preventing it from binding to platelet-derived growth factor receptor (PDGFR), which is a receptor tyrosine kinase that shares a similar binding site to KIT. It took Blueprint a mere 12 months to go from its first hit to BLU-808.
Candidate: GSK3882347
Presenter: Laurel Mydock-McGrane, Fimbrion Therapeutics/GSK
Target: Bacterial FimH protein
Disease: Uncomplicated urinary tract infections
Clinical: Phase 1b (NCT05138822)
Related: “Mannosides Fight Urinary Infections”
Notes: Unlike antibiotics, mannosides like GSK3882347 don’t kill bacteria. Rather, Mydock-McGrane said, they “disarm” them. GSK3882347’s fluorines proved to be key in achieving the desired properties for this drug candidate.
Candidate: MZE829
Presenter: Sarah Bronner, Maze Therapeutics
Target: Apolipoprotein L1 (APOL1)
Disease: APOL1-mediated chronic kidney disease
Clinical: Phase 2 (NCT06830629)
Related: “Maze Therapeutics Raises $191 Million to Figure Out Why Some Mutations Cause Genetic Disease, and Others Don’t”
Notes: MZE829’s pharmacophore was developed with Schrödinger’s pharmacophore modeling tool, Phase, showing that computational strategies can still be effective in the absence of a target’s crystal structure.
Candidate: RTY-406
Presenter: Nathan Fuller, Rectify Pharmaceuticals
Target: Hepatocyte transporters ABCB4 and BSEP
Disease: Primary sclerosing cholangitis
Clinical: Phase 1
Related: “Rectify Launches with $100 Million to Drug ABC Transporters”
Notes: Rectify is pursuing a novel modality in which small molecules are used to fix misbehaving proteins. Rectify calls these PFMs, for positive functional modulators. Using conformational restriction in RTY-406 boosted its potency.
Candidate: PF-07976016
Presenter: Kevin J. Filipski, Pfizer
Target: Glucose-dependent insulinotropic polypeptide receptor (GIPR)
Disease: Obesity
Clinical: Phase 2a (NCT06717425), discontinued
Related: “New Weight-Loss Drugs Could Shift the Scales”
Notes: In making PF-07976016, Pfizer scientists went from a screening campaign to regulatory toxicology studies that enabled investigational new drug approval in about 11 months. It was a Herculean effort that included 30 synthetic chemists who synthesized more than 11,000 molecules. “We had permission to fail, which I think was part of the success,” Filipski said.
