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| Targets |
MP-07-66 targets the SET-PP2A complex, a protein-protein interaction that inhibits PP2A activity. SET (also known as I2PP2A) is an oncoprotein that binds to and inhibits PP2A, a major serine/threonine phosphatase that regulates numerous cellular processes including cell cycle progression, apoptosis, and signal transduction. In many cancers, including chronic lymphocytic leukemia (CLL), SET is overexpressed, leading to PP2A inhibition and enhanced survival and proliferation of malignant cells. MP-07-66 disrupts the SET-PP2A interaction, thereby reactivating PP2A enzymatic activity. Reactivated PP2A dephosphorylates key oncogenic proteins, leading to cell cycle arrest, apoptosis, and reduced tumor growth. Unlike FTY720, which also targets SET-PP2A but has immunosuppressive effects through S1P receptor modulation, MP-07-66 is devoid of S1P receptor activity, providing a more selective anticancer mechanism.
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| ln Vitro |
In vitro, MP-07-66 effectively disrupts the SET-PP2A complex and reactivates PP2A in CLL cells and other cancer cell lines. This reactivation results in decreased phosphorylation of PP2A substrates, including AKT, ERK, and other oncogenic signaling proteins. The compound induces apoptosis in CLL cells, as demonstrated by increased Annexin V staining, caspase activation, and PARP cleavage. MP-07-66 shows potent antiproliferative activity against CLL cells with minimal effects on normal B cells, suggesting selectivity for malignant cells. The compound also exhibits activity against other cancer cell lines where SET is overexpressed, including solid tumors. In combination with conventional chemotherapeutics, MP-07-66 shows synergistic effects, enhancing the sensitivity of cancer cells to treatment. The compound's ability to reactivate PP2A without immunosuppression makes it a promising tool for cancer research.
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| ln Vivo |
In vivo, MP-07-66 has demonstrated antitumor efficacy in preclinical models of chronic lymphocytic leukemia. In mouse xenograft models, administration of the compound results in significant tumor growth inhibition and improved survival. Pharmacodynamic studies confirm PP2A reactivation in tumor tissues, with reduced phosphorylation of downstream targets. Unlike FTY720, MP-07-66 does not cause lymphopenia or immunosuppression, as it does not modulate S1P receptors. This provides a significant safety advantage, as immunosuppression is a major side effect of FTY720 and other S1P receptor modulators. The compound is well-tolerated in vivo at therapeutic doses, with no significant body weight loss or organ toxicity observed. Its efficacy and favorable safety profile support further development as a targeted therapy for CLL and other SET-overexpressing cancers.
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| Enzyme Assay |
The in vitro SET-PP2A disruption assay for MP-07-66 typically uses purified SET protein and PP2A enzyme or cell lysates from CLL cells. The assay is performed in 96-well plates containing PP2A substrate (e.g., phosphorylated peptide or p-nitrophenyl phosphate) and varying concentrations of MP-07-66 (typically 0.1 nM to 100 µM). The reaction is initiated by adding PP2A and incubated at 37°C for 30-60 minutes. Phosphatase activity is measured by colorimetric detection of released phosphate or by fluorescence using a fluorogenic substrate. The ability of MP-07-66 to disrupt the SET-PP2A complex is confirmed by co-immunoprecipitation or pull-down assays, where the compound is incubated with SET and PP2A, and the amount of SET bound to PP2A is quantified by Western blotting. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) can be used to measure binding affinity of MP-07-66 to SET or the SET-PP2A complex. Positive controls (FTY720) and negative controls (vehicle) are included in each assay.
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| Cell Assay |
For in vitro cellular assays, CLL cells (primary patient samples or cell lines such as MEC-1 or JVM-2) are treated with MP-07-66 at concentrations ranging from 0.1 to 100 µM for 24-72 hours. PP2A activity is measured in cell lysates using a commercial PP2A activity assay kit. Protein phosphorylation levels (e.g., p-AKT, p-ERK, p-STAT3) are assessed by Western blotting. Apoptosis is quantified by Annexin V/PI staining, caspase 3/7 activity assays, and PARP cleavage detection. Cell viability is evaluated using CellTiter-Glo or MTT assays. For combination studies, the compound is tested with chemotherapeutic agents (e.g., fludarabine, ibrutinib, or venetoclax) to assess synergy using combination index calculations. All experiments include appropriate controls (vehicle, FTY720 as a positive control for PP2A reactivation) and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice (e.g., NSG or SCID) are inoculated intravenously or subcutaneously with CLL cells (e.g., MEC-1 or primary CLL cells). When tumors are established or engraftment is confirmed, mice are randomized into treatment groups (n=5-10 per group). MP-07-66 is administered orally or intraperitoneally at doses ranging from 10 to 100 mg/kg, typically once or twice daily, for 14-28 days. Tumor burden is monitored by bioluminescence imaging (if luciferase-expressing cells are used) or by measuring tumor volume with calipers. Body weight and clinical signs are monitored for toxicity. At study endpoint, blood and tissues are harvested for pharmacokinetic analysis, PP2A activity measurement, and histopathological examination. Survival studies are performed using KaplaneMeier analysis. Pharmacodynamic markers including PP2A activity and phosphorylation of downstream targets are assessed in tumor and spleen tissues.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of MP-07-66 have been characterized in preclinical species. Following oral administration, the compound shows moderate oral bioavailability (approximately 40-60%) with a Tmax of 1-2 hours. Plasma half-life ranges from 3-6 hours, supporting once- or twice-daily dosing in preclinical studies. The compound distributes into tissues including spleen, lymph nodes, and bone marrow, consistent with its intended use for hematological malignancies. Plasma protein binding is approximately 70-80%. Metabolism is primarily hepatic, with CYP450-mediated oxidation and glucuronidation as major pathways. The compound demonstrates moderate clearance and a volume of distribution consistent with extensive tissue distribution. Pharmacokinetic/pharmacodynamic relationships demonstrate that plasma concentrations above the in vitro effective concentration are maintained for a sufficient duration to achieve antitumor efficacy. Further PK studies are ongoing to fully characterize the compound's disposition.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of MP-07-66 have been conducted in rodents. In acute toxicity studies, the compound is well-tolerated at doses up to 200 mg/kg with no mortality or significant adverse effects. In 14-28 day repeat-dose studies, the no-observed-adverse-effect level (NOAEL) is established at approximately 50 mg/kg/day in mice. At higher doses, mild gastrointestinal disturbances and transient liver enzyme elevations are noted. Importantly, unlike FTY720, MP-07-66 does not cause lymphopenia or immunosuppression at therapeutic doses, confirming its lack of S1P receptor activity. No significant hematological abnormalities, organ toxicity, or histopathological changes are observed at therapeutic doses. The compound shows no evidence of genotoxicity in standard Ames test or micronucleus assays. Cardiotoxicity risk appears low based on hERG channel inhibition studies. The safety profile supports further preclinical and potential clinical development.
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| References | |
| Additional Infomation |
MP-07-66 is a research compound developed for PP2A reactivation as a therapeutic strategy in cancer, particularly chronic lymphocytic leukemia. It is a novel FTY720 analog that lacks immunosuppressive effects, providing a more targeted approach to anticancer therapy. The compound's mechanism involves disruption of the SET-PP2A complex, leading to PP2A reactivation and subsequent apoptosis of cancer cells. MP-07-66 has not yet entered clinical trials but shows promise as a preclinical candidate for hematological malignancies and potentially other SET-overexpressing cancers. Its favorable safety profile, oral bioavailability, and efficacy in preclinical models support further development. The compound is available for research purposes only and is not approved for human use. Ongoing studies are exploring its potential in combination with other targeted therapies and in additional cancer types.
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| Molecular Formula |
C19H33NO3
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|---|---|
| Molecular Weight |
323.470226049423
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| Exact Mass |
323.246
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| CAS # |
1938056-90-6
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| PubChem CID |
154113489
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| Appearance |
Colorless to light yellow ointment
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
23
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| Complexity |
249
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCOC1=CC=C(C=C1)CNCC(OCC)OCC
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| InChi Key |
WBCMPXCRPPCZSO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H33NO3/c1-4-7-8-9-14-23-18-12-10-17(11-13-18)15-20-16-19(21-5-2)22-6-3/h10-13,19-20H,4-9,14-16H2,1-3H3
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| Chemical Name |
2,2-diethoxy-N-[(4-hexoxyphenyl)methyl]ethanamine
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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 : ~250 mg/mL (~772.87 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0915 mL | 15.4574 mL | 30.9148 mL | |
| 5 mM | 0.6183 mL | 3.0915 mL | 6.1830 mL | |
| 10 mM | 0.3091 mL | 1.5457 mL | 3.0915 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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