IPN-60090 是一种具有口服活性和高选择性的谷氨酰胺酶 1GLS1的抑制剂 (IC50=31 nM)，对 GLS-2 无活性。IPN-60090 在体内表现出优良的物理化学和药代动力学特性。IPN-60090 可用于实体肿瘤的研究，如肺癌和卵巢癌。
| 生物活性 | IPN-60090 is an orally active and highly selective inhibitor ofglutaminase1 (GLS1;IC50=31 nM), with no activity observed against GLS-2. IPN-60090 exhibits excellent physicochemical and pharmacokinetic propertiesin vivo. IPN-60090 can be used for solid tumors research, such as lung and ovarian cancers[1][2]. |
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体外研究
(In Vitro) | There are two known isoforms of glutaminase: GLS-1 (also called kidney-type or KGA), and GLS-2 (also called liver-type or LGA). GLS-1 is ubiquitous and GLS-2 expression appears limited primarily to the liver.
In a dual-coupled enzyme assay, IPN60090 inhibits purified recombinant human GLS-1 (GAC isoform) with an IC50of 31 nM, and has no activity against GLS-2, with an IC50of >50000 nM[2].
IPN60090 inhibits the proliferation of A549 cells with an IC50of 26 nM[2].
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体内研究
(In Vivo) | IPN60090 (3 mg/kg for i.v.; 10 mg/kg for p.o.) has excellent pharmacokinetic properties, with CL=4.1 mL/min/kg, t1/2=1 hour, Cmax=19 μM, F%=89%[2].
IPN-60090 (oral administration; 100 mg/kg; twice daily; 30 days) shows similar efficacy and target engagement to CB-839 (HY-12248) dosed orally at 250 mg/kg twice daily. And the 100 mg/kg BID dose of IPN-60090 is a tolerated dose for the following model study[2].IPN-60090 (oral administration; 100 mg/kg; twice daily; 30 days; monotherapy or in combination with TAK228 (HY-13328)) causes tumor growth inhibition. IPN-60090 alone demonstrates robust in vivo target engagement in a dose-dependent manner. The glutamate/glutamine ratios and the free plasma concentrations of IPN-60090 at 4 hours post-dose on both day 4 and day 28 are all decreased[2]. Furthermore, IPN-60090 in combination with TAK228 strongly causes an 85% tumor growth inhibition, IPN-60090 alone causes a 28% tumor growth inhibition in vivo[2].
| Animal Model: | Female CD-1 mice[2] | | Dosage: | 3 mg/kg for i.v.; 10 mg/kg for p.o. (Pharmacokinetic Analysis) | | Administration: | Intravenous injection and oral administration | | Result: | CL (4.1 mL/min/kg), t1/2(1 hour) for i.v.; Cmax(19 μM), F% (89%) for p.o.. |
| Animal Model: | Ru337 non-small cell lung cancer patient-derived xenograft (PDX) subcutaneous mouse model as monotherapy or in combination[2] | | Dosage: | 100 mg/kg | | Administration: | Oral administration; 100 mg/kg; twice daily; 30 days; monotherapy or in combination with TAK228 | | Result: | Exhibited an improvement in the combination regimen group over either single agent. |
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| Clinical Trial | |
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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 : 31.43 mg/mL(59.02 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.8779 mL | 9.3893 mL | 18.7786 mL | | 5 mM | 0.3756 mL | 1.8779 mL | 3.7557 mL | | 10 mM | 0.1878 mL | 0.9389 mL | 1.8779 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 90%corn oil Solubility: ≥ 3.14 mg/mL (5.90 mM); Clear solution
此方案可获得 ≥ 3.14 mg/mL (5.90 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 31.4 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本网站选购。 |
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