IPN60090

小分子

IPN60090

I649622-5mg

5mg

≥99%

-20°C储存

超低温冰袋运输

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 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 IC 50 of 31 nM, and has no activity against GLS-2, with an IC 50 of >50000 nM. IPN60090 inhibits the proliferation of A549 cells with an IC 50 of 26 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. 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, 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 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 ) 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female CD-1 miceDosage: 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), t 1/2 (1 hour) for i.v.; C max (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 combinationDosage: 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. Form:Solid IC50& Target:IC50: 31 nM (GLS1)

IPN-60090 是一种具有高度选择性的谷氨酰胺酶 1（GLS1；IC 50 =31 nM）口服活性抑制剂，对 GLS-2 没有活性。IPN-60090 在体内表现出优异的理化和药代动力学特性。IPN-60090 可用于

1853164-83-6

C24H27F3N8O3

532.52 g/mol

118627280

CC1=CC(=CC(=N1)CC(=O)NC2=NN=C(C=C2)CC[C@H](CN3C=C(N=N3)C(=O)NC)F)OC4CC(C4)(F)F

1-[(2R)-4-[6-[[2-[4-(3,3-difluorocyclobutyl)oxy-6-methylpyridin-2-yl]acetyl]amino]pyridazin-3-yl]-2-fluorobutyl]-N-methyltriazole-4-carboxamide

1S/C24H27F3N8O3/c1-14-7-18(38-19-10-24(26,27)11-19)8-17(29-14)9-22(36)30-21-6-5-16(31-33-21)4-3-15(25)12-35-13-20(32-34-35)23(37)28-2/h5-8,13,15,19H,3-4,9-12H2,1-2H3,(H,28,37)(H,30,33,36)/t15-/m1/s1

GEHZIZWHNLQFAS-OAHLLOKOSA-N

CC1=CC(=CC(=N1)CC(=O)NC2=NN=C(C=C2)CCC(CN3C=C(N=N3)C(=O)NC)F)OC4CC(C4)(F)F

118627280

DMSO : 31.43 mg/mL (59.02 mM; Need ultrasonic)