标签归档：farudodstat

Farudodstat(Synonyms: ASLAN003)

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Farudodstat (Synonyms: ASLAN003) 纯度: 99.95%

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。

Farudodstat(Synonyms: ASLAN003)

Farudodstat Chemical Structure

CAS No. : 1035688-66-4

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ￥2744 In-stock
5 mg ￥3500 In-stock
10 mg ￥5500 In-stock
25 mg ￥9900 In-stock
50 mg 询价
100 mg 询价

* Please select Quantity before adding items.

Farudodstat 相关产品

•相关化合物库:

  • Drug Repurposing Compound Library Plus
  • Clinical Compound Library Plus
  • Bioactive Compound Library Plus
  • Apoptosis Compound Library
  • Cell Cycle/DNA Damage Compound Library
  • Metabolism/Protease Compound Library
  • Anti-Cancer Compound Library
  • Clinical Compound Library
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  • Drug Repurposing Compound Library
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生物活性

Farudodstat (ASLAN003) is an orally active and potent Dihydroorotate Dehydrogenase (DHODH) inhibitor with an IC50 of 35 nM for human DHODH enzyme. Farudodstat inhibits protein synthesis via activation of AP-1 transcription factors. Farudodstat induces apoptosis and 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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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 IC50 values 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.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Female NOD.Cg-Prkdcscid Il2rgtm1Wjl/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.

Clinical Trial

分子量

356.32

Formula

C19H14F2N2O3
CAS 号

1035688-66-4
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
溶解性数据
In Vitro: 

DMSO : 130 mg/mL (364.84 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
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

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.17 mg/mL (6.09 mM); Clear solution

    此方案可获得 ≥ 2.17 mg/mL (6.09 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2.17 mg/mL (6.09 mM); Clear solution

    此方案可获得 ≥ 2.17 mg/mL (6.09 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Jianbiao Zhou, et al. ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemia. Haematologica. 2019 Nov7;haematol.2019.230482.

    [2]. Marco L. Lolli, et al. Human Dihydroorotate Dehydrogenase (hDHODH) as a new target on Acute Myelogenous Leukemia (AML): Targeting Myeloid Differentiation using Potent and Innovative hDHODH Inhibitors. 23rd Swedish Conference on Macromolecular Structure and Function Tällberg, 14-17 June 2019

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