Drug Hunter Highlights Notable Small Molecules from July Through December 2025

Drug Hunter's Molecules of the Month series from July through December 2025 showcased a diverse pipeline of small molecule drug candidates addressing unmet medical needs across multiple therapeutic areas.

December 2025 selections included BCFTP, Johns Hopkins' orally bioavailable MRGPRX1 PAM that could potentially serve as a non-opioid, neuropathic pain relief agent; relutrigine, Praxis' precision NaV inhibitor that could become the first targeted therapy for certain forms of ultra-rare pediatric epilepsies; and GHP-88310, a broad-spectrum non-nucleoside orthoparamyxovirus polymerase inhibitor. Also featured was romaciclib, a CDK8/19 inhibitor being developed to overcome resistance.

October 2025 molecules included an oral small molecule helicase–primase inhibitor targeting HSV-1 and HSV-2, designed to remain active against viral strains that are resistant or refractory to standard nucleoside analogs; a brain-penetrant small molecule muscarinic agonist that potently activates both M1 and M4 receptors; and a pan-PPAR agonist being developed for MASH, which directly targets intrahepatic fibrosis and also addresses extrahepatic inflammation and metabolic dysfunction.

September 2025 featured the first potent, selective, and orally bioavailable FEN1 inhibitor; a brain-penetrant, nanomolar ClpP activator; and a tricyclic GABA-analog for neuropathic pain. Also featured were an oral small molecule for eosinophilic asthma and a benzofuranyl-pyrazole that targets the "undruggable" MYC oncogene.

August 2025 selections included an oral, brain-penetrant pan-mutant RET degrader designed to overcome G810 solvent-front resistance; TNG260, a selective CoREST/HDAC1 inhibitor that restores anti–PD-1 sensitivity in STK11-deficient nSCLC; and sunobinop, a NOP partial agonist that improved sleep efficiency and maintenance in a Ph. 1 crossover clinical trial. Also featured were RMC-5552, a bi-steric mTORC1 inhibitor that reactivates 4EBP1 to suppress MYC, and seclidemstat, a selective HDAC inhibitor.

July 2025 molecules included obefazimod, a miR-124 upregulator achieving remission in ulcerative colitis trials; osivelotor, a next-generation sickle hemoglobin polymerization inhibitor with improved PK and efficacy over the removed-from-market voxelotor; and JNJ-37822681, a repurposed D₂ antagonist for schizophrenia that also acts as a Kv7 channel opener, opening up potential in epilepsy. Also featured was a potent LOXL2 inhibitor with anti-fibrotic efficacy in hepatic models.