The AACR 2023 first disclosures presented in the Chemistry in Cancer Research’s “New Drugs on the Horizon” sessions are always fascinating. This article contains the structures of all of the novel small molecule first disclosures presented at AACR in the session, along with notes on their significance, and another molecule disclosed in the poster session. This page will continue to be updated. Special thanks to Dr. Julien LeFranc for helping cover all of the first disclosures sessions.
The disclosures of small molecule-based therapeutics included:
- ARV-766: An androgen receptor degrading PROTAC for mCRPC (Arvinas)
- BAY 2965501: A first-in-class a diacylglycerol kinase zeta (lipid kinase) inhibitor for cancer immunotherapy, (Bayer/Nuvisan)
- CFT1946: A CRBN-based oral mutant-selective BRAFV600X degrader (C4 Therapeutics)
- RMC-6291: A tri-complex KRASG12C(ON) inhibitor (Revolution Medicines)
- FX-909: A first-in-class covalent inverse agonist of the PPARG lineage transcription factor (Flare Therapeutics)
- M3913: A potential first-in-class WFS1 transmembrane glycoprotein-targeting unfolded protein response (UPR) inducer (ER stress modulator) (Merck KGaA)
- TNG260: An HDAC1/LSD1/RCOR1 (CoREST) deacetylase complex inhibitor (Tango Therapeutics)
- MRT-2359: A CRBN-based GSPT1 degrader (Monte Rosa Tx)
- BI 907828: An MDM2-p53 protein-protein interaction antagonist related to the Nutlin series (Boehringer Ingelheim)
- EO-3021: A MMAE-based CLDN18.2 ADC (Elevation Oncology)
- ABBV-319: A first-in-class glucocorticoid receptor modulator agonist ADC for B-cell malignancies (AbbVie, SSF)
RMC-6291: a Covalent KRASG12C(ON) Inhibitor
RMC-6291 was presented by Jim Cregg, Director of Medicinal Chemistry at Revolution Medicines in Redwood City. While we’ve previously highlighted this class of molecules in Apr. 2021’s Molecules of the Month (RM-018), and the community voted for it as a 2021 Molecule of the Year nominee, the AACR presentation discloses the clinical candidate for the first time, and delves into some of the discovery story around the molecule. Some highlights from the story appear below.
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