HPK1-IN-7 是一种有效的口服活性HPK1(造血祖细胞激酶1, MAP4K1) 抑制剂(IC50=2.6 nM)，具有优良的家族和激酶组选择性。HPK1-IN-7 对 IRAK4 (59 nM) 和 GLK (140 nM) 具有选择性。HPK1-IN-7 联合抗 PD1 对 MC38 同基因肿瘤模型显示出强大的疗效。
| 生物活性 | HPK1-IN-7 is a potent, orally activeHPK1(hematopoietic progenitor kinase 1, MAP4K1) inhibitor (IC50=2.6 nM) with excellent family and kinome selectivity. HPK1-IN-7 shows selectivity againstIRAK4(59 nM) and GLK (140 nM). HPK1-IN-7 shows robust efficacy against MC38 syngeneic tumor model in combination with anti-PD1[1]. |
| IC50& Target[1] | HPK1 2.6 nM (IC50) | GLK/MAP4K3 140 nM (IC50) | IRAK4 59 nM (IC50) | Fms/CSFR 3.2 nM (IC50) | FLT3 25.4 nM (IC50) | AMPKA1 44.3 nM (IC50) | cKIT 45.7 nM (IC50) | MST1 55.1 nM (IC50) | ICK 65.1 nM (IC50) | MST2 78.5 nM (IC50) |
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体内研究
(In Vivo) | HPK1-IN-7 (100 mg/kg; p.o.; twice daily for 28 days) shows robust enhancement of anti-PD1 efficacy in a syngeneic tumor model of colorectal cancer[1].
HPK1-IN-7 (compound 24) (1 mg/kg; intravenous; mice) is characterized by moderate plasma clearance (43 mL/min/kg) and a large volume of distribution (4.4 L/kg). After oral administration (20 mg/kg), the Cmax was 5.3 μM and the AUC0-24hwas 19 μMoh. The calculated oral bioavailability based on these pharmacokinetics studies is approximately 100%[1].
| Animal Model: | Mice (MC38 syngeneic tumor model)[1] | | Dosage: | 100 mg/kg | | Administration: | Oral; twice daily for 28 days | | Result: | Enhanced the efficacy of anti-PD1 treatment, garnering a 100% cure rate vs a 20% cure rate with anti-PD1 alone. |
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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 : 125 mg/mL(272.65 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.1812 mL | 10.9058 mL | 21.8117 mL | | 5 mM | 0.4362 mL | 2.1812 mL | 4.3623 mL | | 10 mM | 0.2181 mL | 1.0906 mL | 2.1812 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: ≥ 2.08 mg/mL (4.54 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.54 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 *以上所有助溶剂都可在本网站选购。
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