| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg |
| ln Vitro |
By causing cell death, MMRi62 prevents pancreatic ductal glands (PDAC) from proliferating, cloning, and growing generatively [1]. MMRi62 attaches to the cyclic heterodimer of MDM2 and MDM4 (3 nM-100 μM; 4 h). Albino cells are activated and inhibited by MMRi62 (10 nM-1 μM; 72 h), with IC50 values of 0.34 μM (HL60) and 0.22 μM (HL60VR)[2]. In a dose-dependent manner, 5 μM, 10μM; 24 hours) decreases MDM2B autoubiquitination and enhances MDM4 ubiquitination [2]. An E3 ligase modification called MMRi62 causes the substrate preference to change from MDM2 to MDM4 [2]. Cellular fluorescence is transmitted by MMRi62 (5 μM; 24, 72 h) without the aid of p53[2].
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|---|---|
| ln Vivo |
MMRi62 showed anti-activity in an orthotopic xenograft PDAC tumor model, decreasing tumor development in mice by suppressing NCOA4 and mutant p53 transcription [1]. MMRi62 also totally prevents orthotopic tumor development [1].
|
| Cell Assay |
Western Blot Analysis[2]
Cell Types: WT-p53 with MV4-11 cells; 293 cells transfected with MDM2B and MDM4 Tested Concentrations: 2, 2.5, 5, 10, 40, 80, 160 μM Incubation Duration: 24 hrs (hours) Experimental Results: 2 μM Levels of cleaved PARP protein and activated caspase 3 increased in wt-p53 MV4-11 cells for 24 hrs (hours). At 5 μM and 10 μM for 24 hrs (hours), MDM2B autoubiquitination diminished and MDM4 ubiquitination increased. In NALM6 cells, 5 μM induces MDM2-dependent degradation of MDM4 protein. Cell proliferation assay[2] Cell Types: primary AML patient cells, NALM6 cells and NALM6shp53 cells Tested Concentrations: 1, 10, 25 and 50 µM Incubation Duration: 24 hrs (hours) and 72 hrs (hours) Experimental Results: Primary cells induced in 24 hands NALM6 cells induced apoptosis for 72 hrs (hours) in AML patients. |
| References |
[1]. Li J, et al. Small-Molecule MMRi62 Induces Ferroptosis and Inhibits Metastasis in Pancreatic Cancer via Degradation of Ferritin Heavy Chain and Mutant p53. Mol Cancer Ther. 2022 Apr 1;21(4):535-545.
[2]. Lama R, et al. Small molecule MMRi62 targets MDM4 for degradation and induces leukemic cell apoptosis regardless of p53 status. Front Oncol. 2022 Aug 5;12:933446. |
| Molecular Formula |
C21H15CL2N3O
|
|---|---|
| Molecular Weight |
396.27
|
| Exact Mass |
395.0592
|
| Elemental Analysis |
C, 63.65; H, 3.82; Cl, 17.89; N, 10.60; O, 4.04
|
| CAS # |
352693-80-2
|
| Related CAS # |
352693-80-2
|
| Appearance |
Solid
|
| SMILES |
C1=CC=NC(=C1)NC(C2=C(C(=CC=C2)Cl)Cl)C3=C(C4=C(C=CC=N4)C=C3)O
|
| InChi Key |
FMUBUUSODRAEMS-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H15Cl2N3O/c22-16-7-3-6-14(18(16)23)20(26-17-8-1-2-11-24-17)15-10-9-13-5-4-12-25-19(13)21(15)27/h1-12,20,27H,(H,24,26)
|
| Chemical Name |
7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol
|
| Synonyms |
MMRi 62; MMRi62; MMRi-62
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~62.5 mg/mL (~157.7 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 | 2.5235 mL | 12.6177 mL | 25.2353 mL | |
| 5 mM | 0.5047 mL | 2.5235 mL | 5.0471 mL | |
| 10 mM | 0.2524 mL | 1.2618 mL | 2.5235 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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