MI-3454 - ≥99% , CAS No.2134169-43-8

CAS: 2134169-43-8 Cat. No.: M651958 Molecular Weight: 636.73 PubChem CID: 130443890

GRADE & PURITY ≥99%

Storage

Store at 2-8°C

Shipped In

Wet ice

Overview

MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC 50 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

In Vitro

MI-3454 (0.001-10 μM; 7 days) strongly reduces murine bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1 proliferation. 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. MI-3454 markedly reduces the viability of leukemic cells harboring various MLL fusion proteins (MLL-AF9, MLL-AF4, MLL-ENL), with GI 50 values ranging from 7 to 27 nM. MI-3454 blocks the interaction of menin with an MLL1 4–43 fragment encompassing the entire menin binding motif. MI-3454 does not potently inhibit cytochromes P450 (<50% inhibition at 10 μM). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: Murine bone marrow cells transformed with MLL-AF9 or Hoxa9/Meis1 Concentration: 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 7 days Result: Demonstrated strong reduction of cell proliferation. RT-PCRCell Line: Human leukemic cell lines MV-4-11 cells or MOLM13 Concentration: 50 nM Incubation Time: 6 days Result: Led to downregulated expression of HOXA9 and MEIS1 and expression level of other MLL fusion target genes, including MEF2C , DLX2 , HOXA10 , PBX3 , and FLT3 .

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 T 1/2 of 3.2 hours, a C max of 4698 mg/mL for PO . MI-3454 exhibits favorable stability in murine and human liver microsomes (t 1/2 =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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 8- to 10-week-old female NSG mice (MV-4-11 xenotransplantation model of MLL leukemia) 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 Dosage: 100 mg/kg (PO) or 15 mg/kg (IV) (Pharmacokinetic Analysis) Administration: PO or IV Result: Had a T 1/2 of 3.2 hours, a C max of 4698 mg/mL for PO. Had a T 1/2 of 2.4 hours, a CL of 2375 mL/hours•kg, and a V ss of 5358 mL/kg for IV.

Form:Solid

IC50& Target:IC50: 0.51 nM (menin-MLL1 interaction)

Specifications

Specifications & Purity

≥99%

Biochemical and Physiological Mechanisms

MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC 50 of 0.51 nM. MI-3454 inhibits proliferation, induces differentiation and complete remission or regression of leukemia in mouse models of MLL1 -rearrange

Storage

Store at 2-8°C

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥99%

Names and Identifiers

• Canonical Smiles: CC1=C(C=CC2=C1C=C(N2CC34CC(C3)(C4)NC=O)C#N)CN5CCC(CC5)NC6=C7C=C(SC7=NC(=N6)NC)CC(F)(F)F
• IUPAC 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
• InChIKey: MBFYNGBMAACLAT-UHFFFAOYSA-N
• 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)
• PubChem CID: 130443890
• Molecular Weight: 636.73

Chemical and Physical Properties

• Solubility: DMSO : 31.25 mg/mL (49.08 mM; Need ultrasonic)