FX-909

FX-909
Legal status
Legal status
  • Investigational
Identifiers
  • 3-(5,7-difluoro-4-oxo-1H-quinolin-2-yl)-4-methylsulfonylbenzonitrile
CAS Number
PubChem CID
Chemical and physical data
FormulaC17H10F2N2O3S
Molar mass360.33 g·mol−1
3D model (JSmol)
  • CS(=O)(=O)C1=C(C=C(C=C1)C#N)C2=CC(=O)C3=C(N2)C=C(C=C3F)F
  • InChI=1S/C17H10F2N2O3S/c1-25(23,24)16-3-2-9(8-20)4-11(16)13-7-15(22)17-12(19)5-10(18)6-14(17)21-13/h2-7H,1H3,(H,21,22)
  • Key:RBUBBZVQPHSZEZ-UHFFFAOYSA-N

FX-909 is a drug which acts as a selective inverse agonist at the receptor peroxisome proliferator-activated receptor gamma (PPARγ). It is being investigated as a potential therapeutic agent for a particular form of cancer, urothelial carcinoma. While PPARγ agonists are commonly used in the treatment of diabetes and have been investigated as anti-cancer drugs for other forms of cancer, in the case of urothelial carcinoma, PPARγ is a master regulator of cell differentiation in the tissue forming the inner lining of the bladder and urinary system, and PPARγ inverse agonists can inhibit the growth of tumors derived from these tissues. FX-909 is the first drug of this type to have reached human clinical trials and has performed well in early stage testing, though it has not been approved for medical use.

See also

References

  1. ↑ Deng W, Wang X, Niu X, Zhang X, Hou Y, Qin M. Inverse Agonists of Peroxisome Proliferator-Activated Receptor Gamma: Advances and Prospects in Cancer Treatment. J Med Chem. 2025 May 8;68(9):9084-9100. doi:10.1021/acs.jmedchem.5c00673 PMID 40300091
  2. ↑ Laughlin ZT, Arifova L, Munoz-Tello P, Yu X, Giridhar MNK, Dong J, Harp JM, Zhu D, Kamenecka TM, Kojetin DJ. Structural Basis of PPARγ-Mediated Transcriptional Repression by the Covalent Inverse Agonist FX-909. J Med Chem. 2025 Aug 28;68(16):17587-17597. doi:10.1021/acs.jmedchem.5c01252 PMID 40797371
  3. ↑ First-of-Its-Kind PPARG Inhibitor Shows Compelling Activity. Cancer Discov. 2026 Jan 12;16(1):OF1. {doi:10.1158/2159-8290.CD-NW2025-0103 PMID 41289426
  4. ↑ Galsky MD, Mantia C, Bowden M, Bellmunt J, Garmezy B, Iyer G, Petrylak DP, Rasco D, Gupta S, Rodriguez-Rivera I, Mikhailov Y, Joshi A, Nguyen PA, Kakrecha B, Tepper J, Costa AM, McCrone C, Rossi AP, Mertz JA, Gjini E, Meyers ML, Milowsky MI, Gao X. A small-molecule inverse agonist of PPARγ for advanced solid tumors: a phase 1 trial. Nat Med. 2026 Apr;32(4):1249-1256. doi:10.1038/s41591-026-04263-3 PMID 41760953
  5. ↑ Stuckey JI, Mertz JA, Wilson JE, Williamson KE, Li Y, Kuljanin M, Setser JW, DeLaBarre B, Chenail G, Nguyen PA, Scott ME, Geier MJ, Bailey CM, Motley WW, Audia JE, Sims RJ 3rd. Covalent PPARγ inverse agonism by FX-909 reveals mechanistic insights into therapeutic targeting of PPARγ/RXRα-activated urothelial carcinoma. Cell Chem Biol. 2026 Jun 18;33(6):837-847.e14. doi:10.1016/j.chembiol.2026.04.017 PMID 42208535