Safusidenib (AB-291; DS-1001) is an orally bioavailable, selective mutant IDH1 inhibitor. Safusidenib strongly inhibits mutant IDH1 but not wild-type IDH1. Safusidenib impairs tumor activity in chondrosarcoma[1]. Safusidenib exhibits activity against IDH1R132H, and IDH1R132C with IC50s of 15, and 130 nM in assays without any preincubation, respectively[2].
in vivo
Safusidenib (DS-1001b) has antineoplastic activity in JJ012 xenografts. Continuous administration of Safusidenib (mixed with sterilized pellet food and fed continuously for 6 weeks) impairs tumor growth in xenograft mice[1].
Animal Model:
NOD-SCID bearing JJ012 xenograft[3]
Dosage:
Mixed with sterilized pellet food (CRF-1; Oriental Yeast) and fed ad libitum for 6 weeks.
Mixed with sterilized pellet food (CRF-1; Oriental Yeast) and fed ad libitum for 6 weeks.
Administration:
Fed continuously starting at 3 weeks
Result:
Continuous administration significantly impaired tumor growth in JJ012 xenograft mice.
IC 50
IDH1
References
[1] Makoto Nakagawa, et al. Selective inhibition of mutant IDH1 by DS-1001b ameliorates aberrant histone modifications and impairs tumor activity in chondrosarcoma. Oncogene. 2019 Oct;38(42):6835-6849. DOI:10.1038/s41388-019-0929-9 [2] Yukino Machida, et al. A Potent Blood-Brain Barrier-Permeable Mutant IDH1 Inhibitor Suppresses the Growth of Glioblastoma with IDH1 Mutation in a Patient-Derived Orthotopic Xenograft Model. Mol Cancer Ther. 2020 Feb;19(2):375-383. DOI:10.1158/1535-7163.MCT-18-1349
