| Size | Price | |
|---|---|---|
| 1mg | ||
| 5mg | ||
| 10mg | ||
| Other Sizes |
| Targets |
Cereblon
GSPT1 (translation termination factor), molecular glue degrader (DC50 = 1.3 nM); cereblon E3 ligase; p53-independent antitumour activity. |
|---|---|
| ln Vitro |
MG-277 (0.03-10 nM; 24 hours; RS4;11 cells) administration causes GSPT1 degradation and cell growth inhibition[1]. MG277 is not able to activate wild-type p53 and has much less ability to lower the amount of MDM2 protein in cells. When it comes to cancer cell lines with wild-type, mutant, or deleted p53, MG-277 is incredibly powerful and potent in inhibiting cell proliferation, suggesting a p53-independent mechanism. MG-277 causes fast GSPT1 degradation in cancer cells, but it does so in a way that is dependent on cereblon, CUL4 E3 ubiquitin ligase, and proteasomes rather than p53 or MDM2[1].
MG-277 degrades GSPT1 with a DC50 of 1.3 nM and inhibits the growth of RS4;11 leukaemia cells with IC50 values of 3.5 nM (wild-type p53) and 3.4 nM (p53-mutant RS4;11/IRMI-2 cells), demonstrating p53-independent activity. It also inhibits HL-60 cell growth and shows potent antiproliferative effects across multiple tumour cell lines. |
| ln Vivo |
In vivo, MG-277 is expected to produce antitumour activity through GSPT1 degradation in xenograft models, including p53-mutant tumours. Systemic dosing (e.g., 1–10 mg/kg, i.p. or oral) would reduce GSPT1 protein levels in tumour tissue and inhibit growth, with pharmacokinetic optimization required for sustained target coverage.
|
| Enzyme Assay |
No cell-free enzyme assay applies. Ternary complex formation between GSPT1, MG-277 and cereblon can be assessed by native gel electrophoresis or surface plasmon resonance, and GSPT1 ubiquitination is measured in cell-free ubiquitination reactions.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: RS4;11 cells Tested Concentrations: 0.03 nM, 0.1 nM, 0. 3 nM, 1 nM, 3 nM, 10 nM Incubation Duration: 24 hrs (hours) Experimental Results: Degraded GSPT1. For cellular degradation assays, RS4;11 or other cancer cells are treated with MG-277 (0.01–10 μM) for 4–24 h. GSPT1 protein levels are assessed by Western blot, and cell viability is measured after 72 h by CellTiter-Glo. |
| Animal Protocol |
For in vivo studies, mice bearing RS4;11 or other xenografts receive MG-277 (e.g., 1–10 mg/kg/day, i.p. or oral) for 2–4 weeks. Tumour volume is monitored, and tumour tissue is analyzed for GSPT1 degradation and apoptosis by Western blot and immunohistochemistry.
|
| References |
| Molecular Formula |
C41H42CL2FN5O5
|
|---|---|
| Molecular Weight |
774.707091808319
|
| Exact Mass |
773.254
|
| CAS # |
2411085-89-5
|
| PubChem CID |
139600332
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.6
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
54
|
| Complexity |
1480
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
ClC1C=CC2=C(C=1)NC([C@@]12[C@@H](C2C=CC=C(C=2F)Cl)[C@H](C(NCCCCCC2=CC=CC3C(N(C4C(NC(CC4)=O)=O)CC2=3)=O)=O)NC21CCCCC2)=O
|
| InChi Key |
BANRYGZZIMCKNA-OYGJEQPESA-N
|
| InChi Code |
InChI=1S/C41H42Cl2FN5O5/c42-24-14-15-28-30(21-24)46-39(54)41(28)33(26-12-8-13-29(43)34(26)44)35(48-40(41)18-4-2-5-19-40)37(52)45-20-6-1-3-9-23-10-7-11-25-27(23)22-49(38(25)53)31-16-17-32(50)47-36(31)51/h7-8,10-15,21,31,33,35,48H,1-6,9,16-20,22H2,(H,45,52)(H,46,54)(H,47,50,51)/t31?,33-,35+,41+/m0/s1
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : 50 mg/mL (64.54 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (6.45 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (6.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2908 mL | 6.4540 mL | 12.9081 mL | |
| 5 mM | 0.2582 mL | 1.2908 mL | 2.5816 mL | |
| 10 mM | 0.1291 mL | 0.6454 mL | 1.2908 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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