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| Targets |
The primary target of ABL127 is protein phosphatase methylesterase-1 (PME-1). PME-1 is an enzyme that demethylates the catalytic subunit of protein phosphatase 2A (PP2A), thereby inactivating it. By covalently inhibiting PME-1, ABL127 prevents the demethylation of PP2A, maintaining its activity. PP2A is a tumor suppressor phosphatase that regulates various signaling pathways involved in cell growth and proliferation.
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| ln Vitro |
In this experiment, three known PME-1 inhibitors were examined, and thermal shifts of 100 μM ABL127 were found. The protein melting temperature was also seen to alter when 25 or 50 μM ABL127 was used. Similar to PME-1 depletion using shRNA, it was discovered that treating Ishikawa cells with ABL127 and AMZ-30 dramatically decreased cell growth. Additionally, it was shown that ABL127 or AMZ-30 treatment had a dose-dependent effect on cell invasion in ECC-1 cells. Protein phosphatase 2A (PP2A) activity in EC cells treated with ABL127 increases significantly to about 45%, but treatment with AMZ-30 causes PP2A activity to increase just slightly to around 10% [1].
In vitro, ABL127 is a potent and selective inhibitor of PME-1. It has cellular IC₅₀ values of 6.4 nM and 4.2 nM in HEK293T and MDA-MB-231 cells, respectively. By inhibiting PME-1, ABL127 increases PP2A methylation and activity, reducing demethylated PP2A by up to ~85%. It suppresses cancer cell proliferation and invasive growth at recommended concentrations of ~100 nM. |
| ln Vivo |
These pilot investigations did not allow for the assessment of significant reductions in tumor burden [1]. Brain PME-1 is inactivated by ABL127, according to gel-based study, however accurate measurement of the degree of inactivation is hampered by overlapping serine hydrolase activity [2].
In vivo, ABL127 has been used as a chemical probe for PP2A/PME-1 signaling. Its ability to inhibit PME-1 and activate PP2A makes it a valuable tool for studying the role of this phosphatase in tumor suppression and other biological processes. The compound's in vivo efficacy and pharmacokinetic properties have been characterized in preclinical studies. |
| Enzyme Assay |
In vitro enzyme assays for ABL127 measure its inhibition of PME-1 activity. The enzyme is incubated with a substrate, and the demethylation of PP2A is measured. The compound's IC₅₀ is determined from dose-response curves. Selectivity over other serine hydrolases is assessed by testing against a panel of enzymes. These assays confirm its mechanism as a potent and selective covalent inhibitor.
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| Cell Assay |
In vitro cell-based assays for ABL127 evaluate its effects on PP2A activity and cell proliferation. Cells are treated with the compound, and the methylation status of PP2A is measured by Western blot using specific antibodies. Cell proliferation is assessed using MTT or CellTiter-Glo assays. The compound's effects on cell migration and invasion can also be evaluated.
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| Animal Protocol |
In vivo animal studies for ABL127 are conducted to evaluate its pharmacological effects. The compound is typically administered via intraperitoneal or oral routes. Pharmacodynamic studies assess the inhibition of PME-1 and the increase in PP2A activity in target tissues. Efficacy studies may be performed in tumor models to evaluate its anti-cancer effects. Pharmacokinetic studies determine the compound's half-life and bioavailability.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of ABL127 have been characterized in preclinical studies. Its molecular weight is 332.35 g/mol. The compound is soluble in DMSO (≥5 mg/mL) and should be stored as a powder at -20°C for up to 3 years. Further details on its half-life, Cmax, and bioavailability are available from the primary research literature.
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| Toxicity/Toxicokinetics |
The toxicity profile of ABL127 has not been extensively detailed in the available literature. It is classified for research use only and not for human consumption. At concentrations above 1 µM, broader serine-hydrolase off-targets may emerge. Standard safety precautions for handling covalent inhibitors should be followed.
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| References |
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| Additional Infomation |
Additional information: ABL127 is also known as ML174. It is a selective covalent inhibitor of PME-1. The compound is used as a chemical probe for PP2A/PME-1 signaling and tumor-suppressor phosphatase research. It has cellular IC₅₀ values in the low nanomolar range. This product is for research use only and is not approved for clinical or therapeutic applications.
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| Molecular Formula |
C17H20N2O5
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| Molecular Weight |
332.351104736328
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| Exact Mass |
332.137
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| CAS # |
1073529-41-5
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| PubChem CID |
24856225
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| Appearance |
Colorless to off-white oil
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
422.8±48.0 °C at 760 mmHg
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| Flash Point |
209.5±29.6 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.586
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| LogP |
2.78
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
525
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1(C(OC)=O)C(=O)[C@@](C2CCCC2)(C2=CC=CC=C2)N1C(OC)=O
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| InChi Key |
ZRHWCAFAIHTQKD-KRWDZBQOSA-N
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| InChi Code |
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
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| Chemical Name |
dimethyl (3R)-3-cyclopentyl-4-oxo-3-phenyldiazetidine-1,2-dicarboxylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~300.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.52 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0089 mL | 15.0444 mL | 30.0888 mL | |
| 5 mM | 0.6018 mL | 3.0089 mL | 6.0178 mL | |
| 10 mM | 0.3009 mL | 1.5044 mL | 3.0089 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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