| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
|
| ln Vitro |
The proliferation of myeloid cells transformed with MLL-AF9 or Hoxa9/Meis1 is significantly inhibited by MI-3454 (0.001-10 μM; 7 days) [1]. In the human blood cell line, MI-3454 (50 nM; 6 days) induces MV-MI-3454 fusion, which dramatically lowers the viability of several leukocytes carrying MLL proteins (MLL-AF9, MLL-AF4, MLL-ENL), GI50 range Expression levels of HOXA9 and MEIS1 in 4-11 cells or MOLM13 [1]. ranges between 7 and 27 nM. Foamy menin is bound by MI-3454 to a segment of MLL14–43 that contains the complete menin binding motif [1]. Cytochrome P450 is not efficiently inhibited by MI-3454 (less than 50% inhibition at 10 μM) [1]. Assay for proliferation [1]
|
|---|---|
| ln Vivo |
MI-3454 causes full leukemia or regression in mixed lineage leukemia 1 (MLL1) rearranged or nucleophosmin 1 (NPM1) variant leukemia models [1]. MI-3454 (120 mg/kg orally; once or twice daily for 7 days) potently halts leukemia progression with once-day dosing [1]. MI-3454 (100 mg/kg sidewall; bid; for 19 days) is effective in leukemia progression throughout treatment and considerably prolongs MOLM13 xenograft MI-3454 causes full remission in a patient-derived xenograft (PDX) model of MLL leukemia or inhibit the progression of leukemia [1]. MI-3454 (100 mg/kg IV or 15 mg/kg IV) has a T1/2 of 3.2 hours and an interface Cmax of 4698 mg/mL [1]. MI-3454 showed good stability in mouse and human liver microsomes (t = 20.4 minutes and 37.1, respectively). MI-3454 has low levels in the brain and CSF fluid, showing its potential to pass the blood-brain barrier. Limited [1].
|
| Cell Assay |
Proliferation assay[1]
Cell Types: Mouse bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1 Tested Concentrations: 0.001, 0.01, 0.1, 1, 10 μM Incubation Duration: 7 days Experimental Results: demonstrated a strong reduction in cell proliferation. RT-PCR[1] Cell Types: Human leukemia cell line MV-4-11 cells or MOLM13 Tested Concentrations: 50 nM Incubation Duration: 6 days Experimental Results: Resulting in down-regulation of the expression of HOXA9 and MEIS1 and the expression levels of other MLL fusion target genes, including MEF2C, DLX2, HOXA10, PBX3 and FLT3. |
| Animal Protocol |
Animal/Disease Models: 8 to 10 weeks old female NSG mice (MV-4 minutes) [1]. -11 MLL leukemia xenograft model) [1]
Doses: 120 mg/kg Route of Administration: oral; Once or twice (two times) daily for 7 days Experimental Results: Once-daily treatment was enough to halt the progression of leukemia. Animal/Disease Models: Female CD-1 mice [1] Doses: 100 mg/kg (PO) or 15 mg/kg (IV) (pharmacokinetic/PK/PK analysis) Route of Administration: PO or IV Experimental Results:T1/2 is 3.2 hrs (hrs (hours)), Cmax PO is 4698 mg/mL. The T1/2 of IV was 2.4 hrs (hrs (hours)), the CL was 2375 mL/hour·kg, and the Vss was 5358 mL/kg. |
| References |
| Molecular Formula |
C32H35F3N8OS
|
|---|---|
| Molecular Weight |
636.7335
|
| Exact Mass |
636.26
|
| CAS # |
2134169-43-8
|
| Related CAS # |
2134169-43-8;MI-3454 HCl;
|
| PubChem CID |
130443890
|
| Appearance |
Light brown to brown solid powder
|
| LogP |
6.1
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
45
|
| Complexity |
1120
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S1C(C([H])([H])C(F)(F)F)=C([H])C2C1=NC(N([H])C([H])([H])[H])=NC=2N([H])C1([H])C([H])([H])C([H])([H])N(C([H])([H])C1([H])[H])C([H])([H])C1C([H])=C([H])C2=C(C=1C([H])([H])[H])C([H])=C(C#N)N2C([H])([H])C12C([H])([H])C(C1([H])[H])(C2([H])[H])N([H])C([H])=O
|
| InChi Key |
MBFYNGBMAACLAT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C32H35F3N8OS/c1-19-20(3-4-26-24(19)9-22(12-36)43(26)17-30-14-31(15-30,16-30)38-18-44)13-42-7-5-21(6-8-42)39-27-25-10-23(11-32(33,34)35)45-28(25)41-29(37-2)40-27/h3-4,9-10,18,21H,5-8,11,13-17H2,1-2H3,(H,38,44)(H2,37,39,40,41)
|
| Chemical Name |
N-[3-[[2-cyano-4-methyl-5-[[4-[[2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]piperidin-1-yl]methyl]indol-1-yl]methyl]-1-bicyclo[1.1.1]pentanyl]formamide
|
| 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~31.25 mg/mL (~49.08 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (7.85 mM) in 20% HP-β-CD 5% Cremophor EL (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5705 mL | 7.8526 mL | 15.7052 mL | |
| 5 mM | 0.3141 mL | 1.5705 mL | 3.1410 mL | |
| 10 mM | 0.1571 mL | 0.7853 mL | 1.5705 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
