Physicochemical Properties
| CAS # | 2851841-61-5 |
| PubChem CID | 168286999 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 40 |
| Complexity | 907 |
| Defined Atom Stereocenter Count | 0 |
| 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 |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | In liver microsomes, menin-MLL inhibitor-22 (1 μM; 60 min) had a low clearance rate and good stability[1]. Menin-MLL inhibitor-22 (0.1–10 μM; 24 h) reduces the expression of HOXA9 and MEIS1 triggered by menin–MLL interaction, while menin–MLL inhibitor–22 (1 and 10 μM; 24 h) suppresses the proliferation of MLL-r Leukemia cells MV4–11. The quantity of CD11b, a myeloid cell differentiation marker, increases in response to menin-MLL inhibitor-22 (1 and 10 μM; 7 d), suggesting that the differentiation arrest of MLL-r leukemia cells has been reversed[1]. Menin-MLL inhibitor-22 (1 and 10 μM; 24 h) produces G0/G1 cell cycle arrest and cell apoptosis[1]. |
| ln Vivo | The MV4;11 subcutaneous xenograft models of MLL-rearranged leukemia demonstrate strong antitumor activity when menin-MLL inhibitor-22 (6 mg/kg and 30 mg/kg; po; every second day for 16 days) is administered[1]. AUC0-t (ng·h/mL) AUC0-∞ (ng·h/ML) ClTotal (ML/H/Kg) VSS (L/Kg) f (%) IV 5 n/A 17.5 7.1 1187 1700 2495 2056 49.3 Po 15.3 15.5 12.7 863.7 14730 23 16.9 Pharmacokinetic Properties in SD Rats[1] |
| Cell Assay |
RT-PCR[1] Cell Types: MLL-r Leukemia cells MV4;11 Tested Concentrations: 0.1, 1, and 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Reversed the over-expressing HOXA9 and MEIS1 induced by menin- MLL interaction, diminished the level of HOXA9 and MEIS1. Apoptosis Analysis[1] Cell Types: MLL-r Leukemia cells MV4;11 Tested Concentrations: 1, and 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished in the population of cells in the S and G2/M phases, arrested cell cycle at G0/G1 phase. |
| Animal Protocol |
Animal/Disease Models: Balb/C Nude mice bearing MV4;11 cell xenografts[1] Doses: 6 mg/kg, 30 mg/kg Route of Administration: Oral gavage; every second day for 16 days Experimental Results: decreased the volume of tumor in mice. |
| References |
[1]. Discovery of Novel, Potent, and Selective Small-Molecule Menin-Mixed Lineage Leukemia Interaction Inhibitors through Attempting Introduction of Hydrophilic Groups. J Med Chem. 2022 Oct 13;65(19):13413-13435. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |