- MI-503
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- $0.00 / 1mg
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2024-04-19
- CAS:1857417-13-0
- Min. Order: 1mg
- Purity: 98%+ HPLC
- Supply Ability: 50g per month
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| Product Name: | MI-503 | | Synonyms: | mi503;mi-503;1-((1H-Pyrazol-4-yl)methyl)-4-methyl-5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-;MI503;MI 503;CS-1946;1H-Indole-2-carbonitrile, 4-methyl-1-(1H-pyrazol-4-ylmethyl)-5-[[4-[[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]-1-piperidinyl]methyl]-;1-((1H-Pyrazol-4-yl)methyl)-4-methyl-5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile;Inhibitor,MI503,inhibit,MI 503,MI-503,Epigenetic Reader Domain | | CAS: | 1857417-13-0 | | MF: | C28H27F3N8S | | MW: | 564.63 | | EINECS: | | | Product Categories: | | | Mol File: | 1857417-13-0.mol |  |
| | MI-503 Chemical Properties |
| Boiling point | 782.9±60.0 °C(Predicted) | | density | 1.48±0.1 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | DMSO : 50 mg/mL (88.55 mM);Water : < 0.1 mg/mL (insoluble) | | pka | 14.10±0.50(Predicted) | | InChIKey | DETOMBLLEOZTMZ-UHFFFAOYSA-N | | SMILES | N1(CC2=CNN=C2)C2=C(C(C)=C(CN3CCC(NC4N=CN=C5SC(CC(F)(F)F)=CC5=4)CC3)C=C2)C=C1C#N |
| | MI-503 Usage And Synthesis |
| Uses | MI-503 is used in the pharmacological inhibition of menin-MLL interaction that blocks progression of MLL leukemia in vivo. | | Biochem/physiol Actions | MI-503 is a highly potent menin-MLL interaction inhibitor (cell-free IC50 = 14.7 nM against 1 nM FITC-MLL(4-13) peptide; cellular IC50 = 220 nM using HEK293 MLL-AF9 fusion transfectants) that targets menin MLL-binding site with high affinity (KD = 9.3 nM by ITC). MI-503 selectively inhibits mixed lineage leukemia (MLL) oncogenic fusion-driven cancer progression in cultures (GI50 from 250 to 570 nM; GI50 >5 μM against cells without MLL gene translocation) and is efficacious against human MLL leukemia MV4; tumor growth in mice in vivo (by 80-100%; 60 mg/kg/day i.p.) with good pharmacokinetic properties, oral bioavailability (73% post 30 mg/kg p.o.), and no adverse effects to the animals. | | in vitro | MI-503 occupies the F9 and P13 pockets on menin, forming a hydrogen bond with Tyr276, and also extends beyond the P13 pocket to form hydrogen bonds with Trp341 and Glu366. Treatment of murine bone marrow cells (BMC) transformed with the mLL-AF9 oncogene with MI-503 results in substantial growth inhibition, with GI50 of 0.22 μM. The cell growth inhibitory effect of MI-503 is time-dependent, with a pronounced impact achieved after 7-10 days of treatment.
| | in vivo |
MI-503 achieves a high level in peripheral blood following a single intravenous or oral dose while also showing high oral bioavailability (75%). MI-503 induces strong tumor growth inhibition with once-daily intraperitoneal (i.p.) administration. Treatment with MI-503 results in an over 80% reduction in MV4, 11 tumor volume, and complete tumor regression in two mice. Ten consecutive days of treatment with MI-503 results in a marked delay in the progression of mLL leukemia in mice and significantly reduces leukemia tumor burden. Treatment with MI-503 and MI-463 leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of mLL fusion proteins substantially upregulated in mLL leukemias.
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| | MI-503 Preparation Products And Raw materials |
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