| Bioactivity | 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. | ||||||||||||
| Target | IC50: 6.4 nM (PME-1 in HEK293T), 4.2 nM (PME-1 in MDA-MB-231) | ||||||||||||
| Invitro | 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]. | ||||||||||||
| In Vivo | 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]. | ||||||||||||
| Name | ABL127 | ||||||||||||
| CAS | 1073529-41-5 | ||||||||||||
| Formula | C17H20N2O5 | ||||||||||||
| Molar Mass | 332.35 | ||||||||||||
| Appearance | Oil | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| 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. |