PGMI-004A-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPGMI-004ACat. No.: HY-101143CAS No.: 1313738-90-7分式: CHFNOS分量: 463.38作靶點(diǎn): Others作通路: Others儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 125 mg/mL (269.76 mM)H2O : 40% PEG300 5% Tween-80

2、45% salineSolubility: 2.08 mg/mL (4.49 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.49 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 PGMI-004A種有效的磷酸油酸變位酶 1 (PGAM1) 抑制劑，IC50 為 13.1 M。IC50 & Target IC50: 13.1

3、 M (PGAM1) 1體外研究 PGMI-004A inhibits PGAM1 with an IC50 of approximately 13.1 M and the Kd value of the PGMI-004A-PGAM1 interaction is determined to be 7.20.7 M from fluorescence-based binding assay. PGMI-004A mayallosterically modulate the enzyme activity of PGAM1. The Ki value is determined to be 3

4、.912.50 M usingDixon plot analysis. The Kd value for protein-ligand interaction is calculated to be 9.42.0 M. Inhibition ofPGAM1 activity by PGMI-004A (20 M) treatment results in decreased 2-PG and increased 3-PG levels inH1299 cells, which could be rescued by treatment with methyl-2-PG. Treatment w

5、ith PGMI-004A (20 M)results in significantly reduced lactate production that is rescued by methyl-2-PG treatment, but has nosignificant effect on intracellular ATP levels. PGMI-004A (20 M) treatment results in decreased oxidativePPP flux and NADPH/NADP+ratio, as well as reduced biosynthesis of lipid

6、s and RNA, and cell proliferation inH1299 cells. PGMI-004A treatment results in decreased cell proliferation of diverse human cancer andleukemia cells, but not control human dermal fibroblasts (HDF), human foreskin fibroblasts (HFF), humanHaCaT keratinocyte cells and human melanocyte PIG1 cells, sug

7、gesting minimal non-specific toxicity ofPGMI-004A in normal, proliferating human cells 1.體內(nèi)研究 The xenograft experiment is performed by injecting H1299 cells to nude mice. Six days post-injection, miceare divided into two groups (n=8/group) and treated with either PGMI-004A (100mg/kg/day) or vehicle

8、for 21days. PGMI-004A treatment results in significantly decreased tumor growth and tumor size in treated micecompared with mice receiving vehicle control. Moreover, treatment with PGMI-004A effectively inhibitsPGAM1 enzyme activity in tumors in vivo in resected tumors from xenograft nude mice 1.PRO

9、TOCOLCell Assay 1 For adherent cell viability assay such as H1299 cells with trypan blue exclusion, 5104 cells are seeded in 6-well plate 24 h before the assay starts and are cultured at 37C. 24 h after seeding, cells are treated withPGMI-004A (5, 10, 20, and 40 M) and incubated at 37C for indicated

10、 times. Cell viability is determined bycounting drug-treated cells compared to DMSO-treated control cells with trypan blue exclusion under amicroscope (40). For MTT cell viability assay of adherent cells, 5103 cells are seeded in 96-well plate 24 hbefore the assay starts and are cultured at 37C. 24

11、h after seeding, cells are treated with PGMI-004A andincubated at 37C for 3 days. Cell viability is determined by using CellTiter96Aqueous One solutionproliferation kit 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Nude

12、 mice (female 6-8-week-old) are subcutaneously injected with 10106 H1299 cells harboring emptyvector on the left flank, and cells with stable knockdown of endogenous hPGAM1 on the right flank,respectively. The tumors are harvested and weighed at the experimental endpoint, and the masses of tumors2/3

13、 Master of Small Molecules 您邊的抑制劑師www.MedChemE(g) derived from cells with and without stable knockdown of endogenous hPGAM1 in both flanks of eachmouse are compared. Statistical analyses are performed by comparison in relation to the control group with atwo-tailed paired Students ttest. For drug eva

14、luation of PGMI-004A using xenograft mice, PGMI-004A isadministered by daily i.p. injection at a dose of 100 mg/kg from 6 days after subcutaneous injection of H1299cells on right flank of each mouse. Tumor growth is recorded by measurement of two perpendiculardiameters of the tumors over a 3-week course 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Hitosugi T, et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell. 2012