MI-3454 - ≥99% , CAS No.2134169-43-8

CAS: 2134169-43-8 Cat. No.: M651958 Formula: C₃₂H₃₅F₃N₈OS Peso molecolare: 636.73 PubChem CID: 130443890

GRADE & PURITY ≥99%

Storage

Store at 2-8°C

Shipped In

Wet ice

Panoramica

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

Specifiche e purezza

≥99%

Meccanismi biochimici e fisiologici

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

Condizioni di conservazione di stoccaggio

Store at 2-8°C

Spedito in

Wet ice

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Tipo di azione

INHIBITOR

Purezza

≥99%

Nomi e identificatori

• Sorrisi canonici: 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
• Peso molecolare: 636.73

Proprietà chimiche e fisiche

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

Domande frequenti

What is the purity of this product?

This product is supplied at ≥99% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at 2–8 °C. Refrigerated storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships chilled on wet ice. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 2134169-43-8, the molecular formula is C32H35F3N8OS, and the molecular weight is 636.73 g/mol. InChIKey MBFYNGBMAACLAT-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.