IPN60090

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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; IC50=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.

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.

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%.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. 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.Animal Model:Female CD-1 mice 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 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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Others

Other Targets

transporter

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1853164-83-6

532.52

C24H27F3N8O3

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 31.43 mg/mL (59.02 mM; 超声助溶 )

CNC(=O)c1cn(C[C@H](F)CCc2ccc(NC(=O)Cc3cc(OC4CC(F)(F)C4)cc(C)n3)nn2)nn1

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(-20℃)

With Ice Pack

≥ 2 years