MI-503 |
Katalog-Nr.GC19247
One-Click Copy Product Info
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MI-503 ist ein hochwirksamer und oral bioverfÜgbarer niedermolekularer Inhibitor der Menin-mLL-Interaktion.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1857417-13-0
Sample solution is provided at 25 µL, 10mM.
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MI-503 is a highly potent and orally bioavailable small molecule inhibitor of the menin-mLL interaction.
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 uM. The cell growth inhibitory effect of MI-503 is time-dependent, with a pronounced effect achieved after 7-10 days of treatment[1].
MI-503 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (75%). MI-503 induces strong inhibition of tumor growth 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 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[1].
References:
[1]. Borkin D, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell. 2015 Apr 13;27(4):589-602.
Cell experiment: | Leukemia cells are treated with MI-503 or 0.25% DMSO and cultured at 37 °C for 7 days. Media is changed at day 4, viable cell numbers are restored to the original concentration and MI-503 are re-supplied. MTT cell proliferation assay kit is then employed, and plates are read for absorbance at 570 nm using a microplate reader[1]. |
Animal experiment: | Mice: For efficacy studies in MV4;11 subcutaneous xenograft mice model, 5×106 cells are injected into the 4-6 week old female BALB/c nude mice. Treatment is started when the tumor size reached ~100 mm3. Vehicle (25% DMSO, 25% PEG400, 50% PBS) or compounds (MI-463 or MI-503) are administrated once daily at designated doses using i.p. injections[1]. |
References: [1]. Borkin D, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell. 2015 Apr 13;27(4):589-602. | |
| Cas No. | 1857417-13-0 | SDF | |
| Canonical SMILES | FC(F)(F)CC(S1)=CC2=C1N=CN=C2NC3CCN(CC4=CC=C(N(CC5=CNN=C5)C(C#N)=C6)C6=C4C)CC3 | ||
| Formula | C28H27F3N8S | M.Wt | 564.63 |
| Löslichkeit | DMSO : 50 mg/mL (88.55 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7711 mL | 8.8554 mL | 17.7107 mL |
| 5 mM | 354.2 μL | 1.7711 mL | 3.5421 mL |
| 10 mM | 177.1 μL | 885.5 μL | 1.7711 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 27 reference(s) in Google Scholar.)