BAY-1436032 is a novel pan-mutant isocitrate dehydrogenase 1 (IDH1) inhibitor.

IDH1^[1]

BAY-1436032 is a novel pan-mutant isocitrate dehydrogenase 1 (IDH1) inhibitor. BAY-1436032 inhibits intracellular (R)-2-hydroxyglutarate (R-2HG) production in mouse hematopoietic cells expressing IDH1R132H or IDH1R132C with IC₅₀s of 60 and 45 nM, respectively. R-2HG levels are not reduced in IDH2R140Q and IDH2R172K expressing mouse hematopoietic cells by BAY-1436032 at concentrations up to 10 μM. Colony growth is inhibited by 50% at a concentration of 0.1 μM BAY-1436032, while concentrations up to 100 μM do not suppress colony growth of patient-derived IDH1 wild-type AML cells. On morphologic evaluation myelomonocytic differentiation of myeloid progenitors is strongly induced by BAY-1436032^[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.

Long-term exposure to once daily oral BAY-1436032 reveals nearly complete suppression of (R)-2-hydroxyglutarate (R-2HG) production with 150 mg/kg BAY1436032. White blood cell counts constantly increase in vehicle-treated mice and, at a lower rate, in animals receiving 45 mg/kg BAY-1436032, while they remain constant in the 150 mg/kg cohort. Hemoglobin levels are slightly lower in the vehicle and 45 mg/kg groups as compare to the 150 mg/kg cohort at day 60, while platelet counts are significantly reduced in vehicle and 45 mg/kg BAY-1436032 treated mice compare to the 150 mg/kg cohort at day 60. All mice receiving 150 mg/kg BAY-1436032 survive with minimal hCD45⁺ cell load in their peripheral blood until the end of observation at day 150 after treatment start (P<0.001), while vehicle-treated animals die from leukemia with a median survival of 91 days. Mice treated with 45 mg/kg BAY-1436032 display intermediate levels of CD14/CD15 expression^[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.

489.53

C₂₆H₃₀F₃N₃O₃

1803274-65-8

Room temperature in continental US; may vary elsewhere.

DMSO : 125 mg/mL (255.35 mM; Need ultrasonic and warming)

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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
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• 1.

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

  Solubility: ≥ 2.5 mg/mL (5.11 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.11 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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% (20% SBE-β-CD in saline)

  Solubility: 2.5 mg/mL (5.11 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (5.11 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.11 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.11 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Chaturvedi A, et al. Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo. Leukemia. 2017 Oct;31(10):2020-2028.

Colony-forming cell (CFC) units are assayed in methylcellulose supplemented with 10 ng/mL IL-3, 10 ng/mL GM-CSF, 50 ng/ mL SCF, 50 ng/mL FLT3-ligand and 3 U/mL EPO. Vehicle or BAY-1436032 is added to methylcellulose containing 10⁵ human mononuclear cells, which are plated in duplicate. Colonies are evaluated microscopically 10 to 14 days after plating by standard criteria^[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.

NSG mice are used and transplanted with primary acute myeloid leukemia (AML) cells from a patient with IDH1R132C mutant AML. Per condition 10 mice are treated with vehicle, 45 or 150 mg/kg body weight BAY-1436032 once daily by oral gavage for 150 days starting 17 days after transplantation. Finally, serum R-2HG levels and human CD45⁺ (hCD45⁺) cells are measured^[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.

• [1]. Chaturvedi A, et al. Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo. Leukemia. 2017 Oct;31(10):2020-2028.