IPN-60090 是一种具有口服活性和高选择性的谷氨酰胺酶 1 GLS1 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。

IPN-60090 is an orally active and highly selective inhibitor of glutaminase 1 (GLS1; IC 50 =31 nM), with no activity observed against GLS-2. IPN-60090 exhibits excellent physicochemical and pharmacokinetic properties in vivo. IPN-60090 can be used for solid tumors research, such as lung and ovarian cancers.

Solid

IC50: 31 nM (GLS1)

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 IC50 of 31 nM, and has no activity against GLS-2, with an IC50 of >50000 nM.
IPN60090 inhibits the proliferation of A549 cells with an IC50 of 26 nM.
has not independently confirmed the accuracy of these methods. They are for reference only.

IPN60090 (3 mg/kg for i.v.; 10 mg/kg for p.o.) has excellent pharmacokinetic properties, with CL=4.1 mL/min/kg, t 1/2 =1 hour, C max =19 μM, F%=89%.
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.
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.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Maria Emilia Di Francesco, et al. Gls1 inhibitors for treating disease. WO2016004404A2.
[2]. Michael J Soth, et al. Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties. J Med Chem. 2020 Nov 12;63(21):12957-12977.

In Vitro: DMSO : 31.43 mg/mL (59.02 mM; Need ultrasonic)配制储备液