SEL24-B489 是有效的、I 型的、口服有效的、PIM和FLT3-ITD的双抑制剂,其对PIM1、PIM2 和 PIM3 的Kd值分别为 2 nM、2 nM、和 3 nM。
生物活性 | SEL24-B489 is a potent, type I, orally active, dualPIMandFLT3-ITDinhibitor, withKdvalues of 2 nM forPIM1, 2 nM forPIM2and 3 nM forPIM3, respectively[1].
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IC50& Target[1] | PIM1 2 nM (Kd) | PIM2 2 nM (Kd) | PIM3 3 nM (Kd) | FLT3-ITD |
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体外研究 (In Vitro) | In MOLM-13 and to a lesser extent in MV4-11 cells, a dose-dependent disruption of cell cycle with especially pronounced depletion of the S phase after treatment with SEL24-B489, accompanied by PARP cleavage and apoptosis was observed[1]. SEL24-B489 causes a profound inhibition of S6 (S235/236), but has little effect on PI3K/mTOR signaling[1]. SEL24-B489 inhibits STAT5 (Ser726) and reduced expression of MCL1, whereas none of the selective inhibitors altered c-MYC abundance or induced PARP cleavage[1].
Cell Viability Assay[1] Cell Line: | AZD1208, AC220 and AraC in AML cell lines. | Concentration: | 0-10 μM. | Incubation Time: | 72 h. | Result: | Decreased viability. |
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体内研究 (In Vivo) | SEL24-B489 (25-100 mg/kg, orally) exhibited activity in AML in vivo models[1]. SEL24-B489 induces apoptosis of DLBCL cell lines in low/sub-micromolar concentrations and exhibits activity in a xenograft model[2].
Animal Model: | SCID/beige mice bearing MV-4-11 tumors (FLT3-ITD+)[1].
| Dosage: | 50, 75 and 100 mg/kg. | Administration: | Orally, twice daily. | Result: | Marked dose – dependent tumor reduction (67%, 74% and 82% tumor growth inhibition (TGI) for 50, 75 and 100 mg/kg daily doses, respectively). |
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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 : 25 mg/mL(56.04 mM;ultrasonic and adjust pH to 2 with HCl) 配制储备液 1 mM | 2.2414 mL | 11.2072 mL | 22.4145 mL | 5 mM | 0.4483 mL | 2.2414 mL | 4.4829 mL | 10 mM | 0.2241 mL | 1.1207 mL | 2.2414 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℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 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: ≥ 2.5 mg/mL (5.60 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.60 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。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (5.60 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.60 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 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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