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| Targets |
MOMIPP targets PIKfyve (also known as Fab1), a phosphoinositide kinase that generates phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a lipid that is essential for endosomal trafficking, lysosomal function, and macropinocytosis. By inhibiting PIKfyve, MOMIPP disrupts the normal dynamics of endosomal membranes, leading to the formation of giant vacuoles that originate from macropinosomes and endosomes. The compound selectively activates the JNK1/2 stress kinase pathway, which results in the phosphorylation of downstream targets such as c-Jun, Bcl-2, and Bcl-xL. This JNK activation is a key mediator of methuosis, as it triggers a cascade of events that culminate in cell death. MOMIPP also causes early disruptions of glucose uptake and glycolytic metabolism, which precede the morphological changes associated with methuosis. This metabolic perturbation further contributes to the cytotoxic effects of the compound.
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| ln Vitro |
At low micromolar concentrations, MOMIPP strongly promotes macrocytosis in cultivated astroblastoma cells, resulting in cell division [1]. 3 μM MOMIPP causes cellular vacuolation in U373 and Hs683 cell lines [1]. 10 μM MOMIPP causes excess nutrients and premature glycolysis disruption. JNK1/2 is specifically activated above complement by MOMIPP, which phosphorylates Bcl-2, Bcl-xL, and c-Jun [2].
In vitro studies have extensively characterized the cellular effects of MOMIPP. At low micromolar concentrations (e.g., 3 μM), MOMIPP induces cell vacuolization in U373 and Hs683 glioblastoma cell lines. At 10 μM, MOMIPP causes disruptions of glucose uptake and glycolytic metabolism. Coincident with these metabolic changes, MOMIPP selectively activates the JNK1/2 stress kinase pathway, resulting in phosphorylation of c-Jun, Bcl-2, and Bcl-xL. Western blot analysis has shown that MOMIPP (10 μM) induces major increases in JNK1/2 phosphorylation after 4 or 24 hours of treatment. The compound's ability to induce methuosis has been confirmed in multiple glioblastoma cell lines, and its effects are dependent on the activation of the JNK signaling pathway. The molecular weight of MOMIPP is 292.33 g/mol, and its molecular formula is C18H16N2O2. It is soluble in DMSO at 15.13 mg/mL (51.76 mM). |
| ln Vivo |
The intraperitoneal injection of MOMIPP (80 mg/kg; once daily; for 15 consecutive days) has modifying effects that prevent the growth of xenografts of astrocytoblastoma in the brain [2].
In vivo, MOMIPP has been evaluated in mouse models of glioblastoma. In athymic CrTac:NCR-Foxn1 mice (female, 7-8 weeks old) bearing intracerebral glioblastoma xenografts, intraperitoneal administration of MOMIPP at 80 mg/kg once daily for 15 consecutive days was moderately effective in suppressing tumor progression. The compound's ability to penetrate the blood-brain barrier is critical for its efficacy in these intracranial models. These in vivo findings demonstrate that MOMIPP can reach therapeutic concentrations in the brain and exert anti-tumor effects, supporting its potential for the treatment of glioblastoma and other brain tumors. However, the compound's moderate efficacy suggests that further optimization or combination with other therapies may be needed to achieve more robust anti-tumor responses. |
| Enzyme Assay |
The in vitro enzyme/receptor binding assays for MOMIPP focus on its inhibition of PIKfyve kinase activity. These assays typically use recombinant PIKfyve enzyme and a lipid substrate, and the phosphorylation of phosphatidylinositol to PI(3,5)P2 is measured in the presence of varying concentrations of MOMIPP. The IC50 for PIKfyve inhibition can be determined from dose-response curves. In addition to PIKfyve, the compound's selectivity against other lipid kinases and related enzymes can be assessed using panel screening. However, detailed IC50 values for PIKfyve inhibition have not been widely published, and MOMIPP is primarily characterized by its cellular effects rather than its direct enzymatic potency.
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| Cell Assay |
Western Blot analysis[2]
Cell Types: U251 Cell Tested Concentrations: 10 μM Incubation Duration: 4 hrs (hours) or 24 hrs (hours) Experimental Results: Activation of JNK stress kinase pathway. Cellular assays for MOMIPP are central to its characterization. The compound's ability to induce macropinocytosis and methuosis is assessed using a combination of microscopy and biochemical techniques. Cells are treated with MOMIPP at various concentrations, and the formation of cytoplasmic vacuoles is visualized by phase-contrast or fluorescence microscopy. The uptake of fluorescent tracers, such as dextran or Lucifer Yellow, can be used to quantify macropinocytosis. Cell viability is measured using standard assays such as MTT or CCK-8. The activation of the JNK signaling pathway is assessed by Western blot analysis using phospho-specific antibodies against JNK1/2, c-Jun, Bcl-2, and Bcl-xL. These cellular assays provide a comprehensive picture of MOMIPP's mechanism of action and its effects on cancer cell biology. |
| Animal Protocol |
Animal/Disease Models: Athymic CrTac:NCR-Foxn1 mice (female, 7-8 weeks) [2]
Doses: 80 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day; for 15 days Experimental Results: Inhibition of glioblastoma in the brain Progress in Cytoma Xenografts. In vivo animal experiments for MOMIPP are conducted in mouse models of glioblastoma. Athymic nude mice are implanted with human glioblastoma cells intracranially to establish tumors that grow within the brain parenchyma. After tumor establishment, MOMIPP is administered intraperitoneally at a dose of 80 mg/kg once daily for 15 consecutive days. Tumor progression is monitored by bioluminescence imaging if the cells are engineered to express luciferase, or by histological analysis at the end of the study. The primary endpoint is tumor volume or burden, and secondary endpoints may include animal survival and body weight changes. These experiments are critical for evaluating the therapeutic potential of MOMIPP in a clinically relevant model of glioblastoma. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of MOMIPP have been partially characterized. The compound is known to penetrate the blood-brain barrier, which is essential for its activity against intracranial tumors. It has a molecular weight of 292.33 g/mol and a molecular formula of C18H16N2O2. The compound is soluble in DMSO at 15.13 mg/mL (51.76 mM) and has a LogP of 3.776. These physicochemical properties are consistent with its ability to cross biological membranes, including the blood-brain barrier. However, detailed ADME parameters such as half-life, clearance, and bioavailability have not been extensively reported in the public domain.
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| Toxicity/Toxicokinetics |
The toxicity profile of MOMIPP has not been comprehensively characterized in the public literature. In animal studies, the compound has been administered at 80 mg/kg once daily for 15 consecutive days without reported severe toxicity. However, comprehensive toxicological evaluations, including genotoxicity, cardiotoxicity, and long-term safety studies, have not been published. As a research compound, MOMIPP is intended for laboratory use only and is not approved for human therapeutic applications.
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| References |
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| Additional Infomation |
MOMIPP is a research compound that has not entered clinical trials or received regulatory approval for therapeutic use. Its primary value lies in its ability to induce methuosis, a non-apoptotic form of cell death, through the inhibition of PIKfyve and activation of the JNK signaling pathway. This unique mechanism makes MOMIPP a valuable tool for studying macropinocytosis, endosomal trafficking, and the biology of cell death in cancer research. The compound's ability to penetrate the blood-brain barrier further enhances its utility for studying glioblastoma and other brain tumors. MOMIPP is also used to investigate the role of glucose metabolism and glycolytic disruption in cancer cell death. Ongoing research may explore its potential as a lead compound for the development of novel cancer therapies that target treatment-resistant tumors through non-apoptotic mechanisms.
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| Molecular Formula |
C18H16N2O2
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| Molecular Weight |
292.3318
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| Exact Mass |
292.121
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| CAS # |
1363421-46-8
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| Related CAS # |
MOPIPP;1485521-76-3
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| PubChem CID |
51039247
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| Appearance |
Yellow to orange solid powder
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| LogP |
3.776
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
417
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C2=C(N1)C=CC(=C2)OC)/C=C/C(=O)C3=CC=NC=C3
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| InChi Key |
UPJCYXIOWHZRLU-GQCTYLIASA-N
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| InChi Code |
InChI=1S/C18H16N2O2/c1-12-15(4-6-18(21)13-7-9-19-10-8-13)16-11-14(22-2)3-5-17(16)20-12/h3-11,20H,1-2H3/b6-4+
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| Chemical Name |
(E)-3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-pyridin-4-ylprop-2-en-1-one
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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 : ~31.25 mg/mL (~106.90 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 | 3.4208 mL | 17.1040 mL | 34.2079 mL | |
| 5 mM | 0.6842 mL | 3.4208 mL | 6.8416 mL | |
| 10 mM | 0.3421 mL | 1.7104 mL | 3.4208 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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