Safusidenib 是一种口服有效的选择性IDH1突变型抑制剂。Safusidenib 强烈抑制突变型 IDH1 但不抑制野生型 IDH1。Safusidenib 会削弱软骨肉瘤中的肿瘤活性。Safusidenib 对IDH1R132H和IDH1R132C具有活性，在没有预孵育的情况下，IC50分别为 15 和 130 nM。

Safusidenib 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 IC 50 s 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; GI 50 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 IC 50 s of 8.4, 11, and 180 nM for IDH1R132H, IDH1R132C, and IDH1WT in assays conducted with a 2-hour preincubation step [2]. Cell Proliferation Assay [1] Cell Line: The IDH1 mutant cell lines JJ012 and L835 cells Concentration: 0.1, 1, and 10 μM Incubation Time: 0, 3, 6, 9, 12, and 15 days Result: Impaired proliferation in both cell lines in a dose-dependent manner. Western Blot Analysis [1] Cell Line: L835 cells Concentration: 0, 1, and 10 μM Incubation Time: 6 weeks Result: Markedly upregulated SOX9 at the protein level.

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.

1898206-17-1

C25H18Cl3FN2O4

535.78

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years