MI-503
- CAS No.
- 1857417-13-0
- Chemical Name:
- MI-503
- Synonyms
- mi503;M1-503;mi-503;CS-1946;MI503;MI 503;Inhibitor,MI503,inhibit,MI 503,MI-503,Epigenetic Reader Domain;1-((1H-Pyrazol-4-yl)methyl)-4-methyl-5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-;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;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]-
- CBNumber:
- CB22747932
- Molecular Formula:
- C28H27F3N8S
- Molecular Weight:
- 564.63
- MDL Number:
- MFCD28506303
- MOL File:
- 1857417-13-0.mol
| 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) |
| form | Solid |
| pka | 14.10±0.50(Predicted) |
| color | White to off-white |
| 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 price
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Usbiological | 456198 | MI-503 | 1857417-13-0 | 1mg | $779 | 2021-12-16 | Buy |
| TRC | M350055 | MI-503 | 1857417-13-0 | 2.5mg | $935 | 2021-12-16 | Buy |
| Biosynth Carbosynth | BM170658 | MI 503 | 1857417-13-0 | 100 | $1100 | 2021-12-16 | Buy |
| ChemScene | CS-6217 | MI-503 99.81% | 1857417-13-0 | 50mg | $1130 | 2021-12-16 | Buy |
| ChemScene | CS-6217 | MI-503 99.81% | 1857417-13-0 | 25mg | $790 | 2021-12-16 | Buy |
MI-503 Chemical Properties,Uses,Production
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.
MI-503 Preparation Products And Raw materials
Raw materials
Preparation Products
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Hubei Chuchang Biotech Co., Ltd. | +undefined15623860702 | info@chuchangbiotech.com | China | 116 | 58 |
| ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | ivan@atkchemical.com | China | 32957 | 60 |
| HANGZHOU CLAP TECHNOLOGY CO.,LTD | 86-571-88216897,88216896 13588875226 | sales@hzclap.com | CHINA | 6312 | 58 |
| Zhejiang J&C Biological Technology Co.,Limited | +1-2135480471 +1-2135480471 | sales@sarms4muscle.com | China | 10473 | 58 |
| Nantong HI-FUTURE Biology Co., Ltd. | +undefined18051384581 | sales@chemhifuture.com | China | 3135 | 58 |
| TargetMol Chemicals Inc. | support@targetmol.com | United States | 38632 | 58 | |
| Hebei Miaoyin Technology Co.,Ltd | +86-17367732028 +86-17367732028 | kathy@hbyinsheng.com | China | 3512 | 58 |
| Wuhan Topule Biopharmaceutical Co., Ltd | +8618327326525 | masar@topule.com | China | 8467 | 58 |
| Zibo Hangyu Biotechnology Development Co., Ltd | +86-0533-2185556 +8617865335152 | Mandy@hangyubiotech.com | China | 10986 | 58 |
| Nanjing Bicbiotechnology Co., Ltd | +86-2552131256 +86-18251840740 | sales@bicbiotech.com | China | 5994 | 58 |
