We asked the drug discovery community to nominate molecules for our annual Molecule of the Year spot based on what you found most technically impressive and impactful.
Here is the final list of the top 10 candidates for 2023’s Molecule of the Year, selected by our readers and reviewers. It's always incredibly difficult to narrow down the group, and even more difficult to pick just one!
These finalists are selected based on technical achievement, scientific contribution, potential clinical impact, and novelty, among other factors.
The 2023 Molecule of the Year candidates include:
MK-0616 (PCSK9) - first oral PCSK9 inhibitor and first mRNA display-derived macrocyclic peptide to demonstrate clinical efficacy
KT-474 (IRAK4) - first clinical heterobifunctional degrader in immunology
orforglipron (GLP-1R) - the most advanced small molecule GLP-1R agonist from Chugai
suzetrigine/VX-548 (NaV1.8) - a non-opioid pain medication with recent positive Ph. III data
resmetirom (THR-beta) - a drug that has a chance at achieving the first approval in NASH, with a PDUFA date of Mar. 14, 2024
ritlecitinib (JAK3/TEC-family) - a kinetically-selective JAK3 covalent inhibitor with profound efficacy in alopecia areata
lirafugratinib/RLY-4008 (FGFR2) - the first isoform-selective FGFR2 inhibitor with kinetic selectivity rationalized by molecular dynamics
RMC-6291 (KRAS G12C) - a clinical tri-complex KRAS G12C inhibitor with a molecular glue mechanism of action
omaveloxolone (Nrf2 activator) - a reversible covalent, CNS-penetrant Nrf2 activator
nirogacestat (gamma-secretase) - the first approval for a gamma-secretase inhibitor
You can click on the links above to read full case studies about each of the molecules to understand more about how they work, how they were discovered, and why they’re important.
Additional nominees with multiple submissions that didn’t make the final list include AbbVie’s ABBV-CLS-484 (targeting PTPN2/N1), a pioneering phosphatase inhibitor for cancer immunology, Novartis’ HRO761 (WRN), the most advanced WRN helicase inhibitor, Karuna Therapeutics’ M1&M4 modulator combination for schizophrenia, Turning Point Therapeutics’ macrocyclic kinase inhibitor, repotrectinib, and the potential best-in-class TTR stabilizer, acoramidis from BridgeBio.
Vote for the #1 2023 Molecule of the Year here!
Check out the past winners here:
2022 Molecule of the Year: BMS’s TYK2 Inhibitor, Deucravacitinib
2021 Molecule of the Year: Pfizer’s CoV-2 Mpro Inhibitor, Paxlovid
2020 Molecule of the Year: Gilead’s HIV Capsid Inhibitor, Lenacapavir
And past nominees here:
For even more inspiration, browse the collection of 120 molecules of the month from 2023 here.
