For research use only. Not for therapeutic Use.
ABL127 is a selective and covalent inhibitor of protein methylesterase 1 (PME-1) with IC50s of 6.4 nM and 4.2 nM in HEK293T and MDA-MB-231 cells, respectively.
Three described PME-1 inhibitors are tested in this assay and a thermal shift with 100 μM ABL127 is detected. Using 25 or 50 μM ABL127 also shows a shift in protein melting temperature. It is found that treatment of Ishikawa cells with ABL127 and AMZ-30 significantly decreases cell proliferation similarly to depletion of PME-1 with shRNA. It is also found that treatment of ECC-1 cells with ABL127 or AMZ-30 affects cell invasion in a dose-dependent manner. The treatment of EC cells with ABL127 leads to a significant ~45 % increase in protein phosphatase 2A (PP2A) activity, while treatment with AMZ-30 leads to a modest ~10 % increase in PP2A activity[1].
No significant decrease in tumor burden can be assessed in these pilot studies[1]. Gel-based profiles indicate that brain PME-1 is inactivated by ABL127, but overlapping serine hydrolase activities preclude a confident assessment of the extent of inactivation[2].
| Catalog Number | I000704 |
| CAS Number | 1073529-41-5 |
| Synonyms | dimethyl (3R)-3-cyclopentyl-4-oxo-3-phenyldiazetidine-1,2-dicarboxylate |
| Molecular Formula | C17H20N2O5 |
| Purity | ≥95% |
| InChI | InChI=1S/C17H20N2O5/c1-23-15(21)18-14(20)17(13-10-6-7-11-13,19(18)16(22)24-2)12-8-4-3-5-9-12/h3-5,8-9,13H,6-7,10-11H2,1-2H3/t17-/m0/s1 |
| InChIKey | ZRHWCAFAIHTQKD-KRWDZBQOSA-N |
| SMILES | COC(=O)N1C(=O)C(N1C(=O)OC)(C2CCCC2)C3=CC=CC=C3 |
| Reference | [1]. Pusey M, et al. Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models. Tumour Biol. 2016 Sep;37(9):11835-11842. [2]. Bachovchin DA, et al. Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors. Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):6811-6. |
