MI-389 free base · Synonyms: MI 389 · MI389

MI-389 is a potent menin-MLL interaction inhibitor (IC50=25 nM) and a CRBN-recruiting, GSPT1-targeted PROTAC degrader.

For research use only. Not for human or veterinary use.

Target PROTACs Eukaryotic Release Factor (eRF) Epigenetic Reader Domain

Research area Cancer

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Data Sheet SDS COA

MI-389 structure

CAS No.: 2222635-92-7

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
25 mg	USD 461.00	BP-02445-25mg	In stock	Get quote
50 mg	USD 740.00	BP-02445-50mg	In stock	Get quote
100 mg	USD 1,180.00	BP-02445-100mg	In stock	Get quote
250 mg	USD 2,360.00	BP-02445-250mg	In stock	Get quote
500 mg	USD 3,776.00	BP-02445-500mg	In stock	Get quote
1 g	Inquire	BP-02445-1g	In stock	Inquire

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Description

MI-389 is a potent menin-MLL interaction inhibitor (IC50=25 nM) and a CRBN-recruiting, GSPT1-targeted PROTAC degrader. MI-389 upregulates myeloid differentiation-related genes that are lowly expressed in primitive hematopoietic progenitor cells, thereby inducing myeloid differentiation phenotypic changes in MLL-rearranged leukemia cells. MI-389 competitively blocks the MG-H1-RAGE interaction to interfere with the AGEs-RAGE pathway, thus alleviating AGEs-induced HUVEC injury . MI-389 can be used in studies related to MLL-rearranged acute leukemia .

Biological activity

In Vitro MI-389 potently inhibits the menin-MLL interaction in cell-free assays, with an IC50 of 25 nM and a Kd of 21 nM for binding to menin. MI-389 (0.74-1.69 μM; 7 days) selectively inhibits the growth of MLL-rearranged leukemia cells (MV4;11, MOLM-13, MLL-AF9 BMCs) with GI50 values ranging from 0.74-1.69 μM, while showing no activity against non-MLL leukemia cells (Jurkat, HM-2 BMCs) after 7 days of treatment. MI-389 (4 μM; 6 days) reverses the MLL fusion-driven gene expression signature in MV4;11 human MLL leukemia cells, downregulating oncogenic MLL target genes and upregulating differentiation-associated genes after 6 days of treatment with 4 μM MI-389. MI-389 (2 μM; 6 days) downregulates oncogenic MLL target genes and upregulates the myeloid differentiation marker MNDA in MOLM-13 human MLL leukemia cells.

Identifiers

SMILES: O=C1C2=C(NCCCCCCNC(C3=C(C)NC(/C=C4C5=CC(F)=CC=C5NC/4=O)=C3C)=O)C=CC=C2C(N1C6C(NC(CC6)=O)=O)=O
InChIKey: VXBLUAKQWQJPAD-QJOMJCCJSA-N

Specifications

MW (average): 654.6874
Formula: C₃₅H₃₅FN₆O₆
CAS No.: 2222635-92-7
Physical state: Solid
Color: Yellow to orange
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder 4°C, stored under nitrogen; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

References

[1].Borkin D, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo[J]. Cancer cell, 2015, 27(4): 589-602.

[2].Feng L, et al. Competitive binding between 4,4'-diphenylmethane-bis(methyl) carbamate and RAGE ligand MG-H1 on human umbilical vein endothelial cell by cell membrane chromatography. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2012 Jan 15;881-882:55-62.

Same target

Search PROTACs

Same research area

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