Product Name :
MI-3454
Description:
MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC50 of 0.51 nM. MI-3454 inhibits proliferation, induces differentiation and complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia through downregulation of key genes involved in leukemogenesis.
CAS:
2134169-43-8
Molecular Weight:
636.73
Formula:
C32H35F3N8OS
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]-1H-indol-1-yl}methyl)bicyclo[1.1.1]pentan-1-yl]formamide
Smiles :
CC1C2C=C(C#N)N(CC34CC(C3)(C4)NC=O)C=2C=CC=1CN1CCC(CC1)NC1N=C(NC)N=C2SC(CC(F)(F)F)=CC2=1
InChiKey:
MBFYNGBMAACLAT-UHFFFAOYSA-N
InChi :
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)
Purity:
≥98% (or refer to the Certificate of Analysis)
Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition :
Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life:
≥12 months if stored properly.
Stock Solution Storage:
0 – 4 oC for 1 month or refer to the Certificate of Analysis.
Additional information:
MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC50 of 0.51 nM. MI-3454 inhibits proliferation, induces differentiation and complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia through downregulation of key genes involved in leukemogenesis.|Product information|CAS Number: 2134169-43-8|Molecular Weight: 636.73|Formula: C32H35F3N8OS|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]-1H-indol-1-yl}methyl)bicyclo[1.1.1]pentan-1-yl]formamide|Smiles: CC1C2C=C(C#N)N(CC34CC(C3)(C4)NC=O)C=2C=CC=1CN1CCC(CC1)NC1N=C(NC)N=C2SC(CC(F)(F)F)=CC2=1|InChiKey: MBFYNGBMAACLAT-UHFFFAOYSA-N|InChi: 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)|Technical Data|Appearance: Solid Power|Purity: ≥98% (or refer to the Certificate of Analysis)|Solubility: DMSO : 31.25 mg/mL (49.08 mM; Need ultrasonic).|Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis|Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.|Shelf Life: ≥12 months if stored properly.|Stock Solution Storage: 0 – 4 oC for 1 month or refer to the Certificate of Analysis.|Drug Formulation: To be determined|HS Tariff Code: 382200|How to use|In Vitro:|MI-3454 (0.001-10 μM; 7 days) strongly reduces murine bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1 proliferation.{{Febuxostat} MedChemExpress|{Febuxostat} Xanthine Oxidase|{Febuxostat} Biological Activity|{Febuxostat} Formula|{Febuxostat} supplier|{Febuxostat} Epigenetics} MI-3454 (50 nM; 6 days) leads to downregulated expression of HOXA9 and MEIS1 in Human leukemic cell lines MV-4-11 cells or MOLM13.{{Xanthan gum} MedChemExpress|{Xanthan gum} {Biochemical Assay Reagents}|{Xanthan gum} Technical Information|{Xanthan gum} References|{Xanthan gum} manufacturer|{Xanthan gum} Cancer} MI-3454 markedly reduces the viability of leukemic cells harboring various MLL fusion proteins (MLL-AF9, MLL-AF4, MLL-ENL), with GI50 values ranging from 7 to 27 nM.PMID:24202965 MI-3454 blocks the interaction of menin with an MLL14–43 fragment encompassing the entire menin binding motif. MI-3454 does not potently inhibit cytochromes P450 (In Vivo:|MI-3454 induces complete remission or regression of leukemia in mouse models of mixed lineage leukemia 1 (MLL1)-rearranged or nucleophosmin 1 (NPM1)-mutated leukemia. MI-3454 (p.o.; 120 mg/kg; one or twice daily for 7 consecutive days) sufficiently blocks leukemia progression by a once-daily treatment. MI-3454 (p.o.; 100 mg/kg; b.i.d.; for 19 consecutive days) effectively blocks leukemia progression during the treatment period and markedly prolongs survival of MOLM13 xenotransplantation model mice. MI-3454 induces complete remission or blocks leukemia progression in patient-derived xenograft (PDX) models of MLL leukemia. MI-3454 (100 mg/kg of PO or 15 mg/kg of IV) has a T1/2 of 3.2 hours, a Cmax of 4698 mg/mL for PO. MI-3454 exhibits favorable stability in murine and human liver microsomes (t1/2=20.4 minutes and 37.1 minutes, respectively). MI-3454 demonstrates lower levels in brain and cerebrospinal fluid, suggesting limited ability to cross the blood-brain barrier.|Products are for research use only. Not for human use.|
