Safusidenib  (Synonyms: AB-291; DS-1001)

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].

Safusidenib (DS-1001b) impairs the proliferation of IDH1-mutated chondrosarcoma cell lines and decreases 2-HG levels^[1].
Safusidenib impairs the proliferation of IDH1 mutant chondrosarcoma cell lines in a dose-dependent manner, whereas Safusidenib has little effect on the proliferation of the IDH wild-type cell lines OUMS27 and NDCS-1; GI₅₀ values for JJ012, L835, OUMS27, and NDCS-1 cells are 81?nM (day 14), 77?nM (6 weeks), >10?μM (day 10), and >10?μM (day 10), respectively^[1].
Safusidenib (1, and 10?μM; for 6 weeks) markedly upregulates SOX9, a key regulator of chondrocyte differentiation, at the protein level^[1].
Safusidenib (1 μM) significantly upregulates CDKN1C at the protein level^[1].
Safusidenib (DS-1001b) exhibits activity against IDH1 or IDH2 enzymes with IC₅₀s of 8.4, 11, and 180 nM for IDH1R132H, IDH1R132C, and IDH1WT in assays conducted with a 2-hour preincubation step^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

535.78

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1898206-17-1

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• [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.  [Content Brief]

  [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.  [Content Brief]