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ChemicalBook--->CAS DataBase List--->2134169-43-8

2134169-43-8

2134169-43-8 Structure

2134169-43-8 Structure
IdentificationBack Directory
[Name]

Formamide, N-[3-[[2-cyano-4-methyl-5-[[4-[[2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]-1-piperidinyl]methyl]-1H-indol-1-yl]methyl]bicyclo[1.1.1]pent-1-yl]-
[CAS]

2134169-43-8
[Synonyms]

MI-3454
Formamide, N-[3-[[2-cyano-4-methyl-5-[[4-[[2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]-1-piperidinyl]methyl]-1H-indol-1-yl]methyl]bicyclo[1.1.1]pent-1-yl]-
[Molecular Formula]

C32 H35 F3 N8 O S
[MOL File]

2134169-43-8.mol
[Molecular Weight]

636.73
Chemical PropertiesBack Directory
[form ]

Solid
[color ]

Light brown to brown
Hazard InformationBack Directory
[Description]

MI-3454 is a 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.
[Uses]

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[1].
[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[1].
? MI-3454 (p.o.; 120 mg/kg; one or twice daily for 7 consecutive days) sufficiently blocks leukemia progression by a once-daily treatment[1].
? 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[1].
? 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[1].
? MI-3454 exhibits favorable stability in murine and human liver microsomes (t1/2=20.4 minutes and 37.1 minutes, respectively)[1].
? MI-3454 demonstrates lower levels in brain and cerebrospinal fluid, suggesting limited ability to cross the blood-brain barrier[1].

Animal Model:8- to 10-week-old female NSG mice (MV-4-11 xenotransplantation model of MLL leukemia)[1]
Dosage:120 mg/kg
Administration:Orally; one or twice daily for 7 consecutive days
Result:A once-daily treatment was sufficient to block leukemia progression.
Animal Model:Female CD-1 mice[1]
Dosage:100 mg/kg (PO) or 15 mg/kg (IV) (Pharmacokinetic Analysis)
Administration:PO or IV
Result:Had a T1/2 of 3.2 hours, a Cmax of 4698 mg/mL for PO.
Had a T1/2 of 2.4 hours, a CL of 2375 mL/hours?kg, and a Vss of 5358 mL/kg for IV.
[References]

[1] Szymon Klossowski, et al. Menin Inhibitor MI-3454 Induces Remission in MLL1-rearranged and NPM1-mutated Models of Leukemia. J Clin Invest. 2020 Feb 3;130(2):981-997. DOI:10.1172/JCI129126
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