MedKoo product information

  LY2874455

Description of LY2874455:  LY2874455 is a novel and potent FGF/FGFR Inhibitor. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship.

Current developer:    Eli Lilly.

LY2874455 is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic.[source:  Mol Cancer Ther; 10(11); 2200-10.]

1. Zhao G, Li WY, Chen D, Henry JR, Li HY, Chen Z, Zia-Ebrahimi M, Bloem L, Zhai  Y, Huss K, Peng SB, McCann DJ. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models. Mol Cancer Ther. 2011 Nov;10(11):2200-10. Epub 2011 Sep 7. PubMed PMID: 21900693.

2.  Preparation of vinyl indazolyl compounds as antitumor agents, By Chen, Daohong; Li, Hong-Yu; Zhao, Genshi. From PCT Int. Appl. (2010), WO 2010129509 A1 20101111.