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。
| 生物活性 | Safusidenib is an orally bioavailable, selective mutantIDH1inhibitor. Safusidenib strongly inhibits mutantIDH1but not wild-typeIDH1. Safusidenib impairs tumor activity in chondrosarcoma[1]. Safusidenib exhibits activity againstIDH1R132H, andIDH1R132CwithIC50s of 15, and 130 nM in assays without any preincubation, respectively[2]. |
体外研究
(In Vitro) | 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; GI50values 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].
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. |
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体内研究
(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 fedad libitumfor 6 weeks.
Mixed with sterilized pellet food (CRF-1; Oriental Yeast) and fedad libitumfor 6 weeks. | | Administration: | Fed continuously starting at 3 weeks | | Result: | Continuous administration significantly impaired tumor growth in JJ012 xenograft mice. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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