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MI-503 is a potent and selective Menin-MLL inhibitor with IC50 of 14.7 nM. MI-503 shows pronounced growth suppressive activity in a panel of human MLL leukemia cell lines(GI50 at 250 nM-570 nM range), but only a minimal effect in human leukemia cell lines without MLL translocations. MI-503 is also very effective in inducing differentiation of MLL leukemia cells and substantially increases expression of CD11b, a myeloid differentiation marker. These effects are accompanied by reduced c-kit (CD117) expression, a marker associated with leukemia stem cells (LSCs).
In vivo, MI-503 blocks hematologic tumors in vivo and reduces MLL leukemia tumor burden. MI-503 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (~75%). Prolonged treatment (38 days) with MI-503 induces no toxicity in mice as reflected by no alterations in the body weight and no morphological changes in liver and kidney tissues.
Mol Biomed. 2025 Nov 15;6:112.
Histone methyltransferase KMT2D targets the SPOP-G3BP1 axis to enhance AR stability and drive castration-resistant prostate cancer progression.
MI-503 purchased from AbMole
| Molecular Weight | 564.63 |
| Formula | C28H27F3N8S |
| CAS Number | 1857417-13-0 |
| Solubility (25°C) | DMSO: ≥ 50 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[2] Laurie K Svoboda, et al. Menin regulates the serine biosynthetic pathway in Ewing sarcoma
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