Farudodstat (ASLAN003) 是一种具有口服活性，有效的二氢乳清酸脱氢酶 (DHODH) 抑制剂，对人 DHODH 酶的IC50为 35 nM。Farudodstat 通过激活 AP-1 转录因子来抑制蛋白质合成。Farudodstat 可以诱导凋亡 (apoptosis)，并在急性髓样白血病 (AML) 异种移植小鼠中大大延长其生存期。
| 生物活性 | Farudodstat (ASLAN003) is an orally active and potentDihydroorotate Dehydrogenase(DHODH)inhibitor with anIC50of 35 nM for human DHODH enzyme. Farudodstat inhibits protein synthesis via activation ofAP-1transcription factors. Farudodstat inducesapoptosisand substantially prolongs survival in acute myeloid leukemia (AML) xenograft mice[1][2]. |
| IC50& Target | IC50: 35 nM (human DHODH enzyme)[1] |
体外研究
(In Vitro) | Farudodstat (0.01-100 μM; for 48 hours) inhibits leukemic cell proliferation. The cell viability is maintained at ~50% at Farudodstat 1 μM and higher[1].
Farudodstat (0.5, 1 μM; for 48 hours) significantly increases cleaved caspase 8[1].
Farudodstat (2, 4 μM; for 96 hours) decreases viability and induces differentiation in primary acute myeloid leukemia blasts and myelodysplastic syndrome samples[1].
Farudodstat (1, 2 μM; pretreatment 1 h before OPP for 1 h) inhibits protein synthesis, as demonstrated by the reduced incorporation of O-propargyl-puromycin (OPP) at protein translation sites in both MOLM-14 and KG-1 cells. Farudodstat causes the downregulation of EIF4B, and RPL6 proteins[1].
Cell Proliferation Assay[1] | Cell Line: | THP-1, MOLM-14 and KG-1 cells | | Concentration: | 0.01, 0.1, 1, 10, 100 μM | | Incubation Time: | For 48 hours | | Result: | Inhibited leukemic cell proliferation of THP-1, MOLM-14 and KG-1 with IC50values of 152 nM, 582 nM, and 382 nM, respectively. |
Western Blot Analysis[1] | Cell Line: | KG-1 and MOLM-14 cells | | Concentration: | 0.5, 1 μM | | Incubation Time: | For 48 hours | | Result: | Significantly increased cleaved caspase 8, increased leakage of cytochrome c from mitochondria into the cytosol and induced cleaved caspase-3 and -7. |
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体内研究
(In Vivo) | Farudodstat (50 mg/kg; oral gavage; once daily; from the day 3 to 30) substantially reduces the number of disseminated tumors and prolongs survival[1].
| Animal Model: | Female NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ, NGS mice (4-6 weeks old) with MOLM-14 cells[1] | | Dosage: | 50 mg/kg | | Administration: | Oral gavage; once daily; from the day 3 to 30 | | Result: | Substantially reduced the number of disseminated tumors and the size of these tumors.
Survival was significantly prolonged. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 130 mg/mL(364.84 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.8065 mL | 14.0323 mL | 28.0647 mL | | 5 mM | 0.5613 mL | 2.8065 mL | 5.6129 mL | | 10 mM | 0.2806 mL | 1.4032 mL | 2.8065 mL |
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