MMH1
Based on 1 Customer Validation
MMH1 is a novel BRD4 molecular glue degrader. MMH1 functions by recruiting the CUL4 DCAF16 ligase to the second bromodomain of BRD4 (BRD4 BD2). MMH1 binds to the JQ1-binding site of BRD4 BD2, acts as a template to covalently modify Cys58 of DCAF16, stabilizes the BRD4-DCAF16 ternary complex, and thereby promotes BRD4 degradation via the CRL4DCAF16 ubiquitin ligase pathway. Using BRD4 BD2 as a structural template, MMH1 covalently modifies Cys87 of GAK and induces the GAK-BRD4 BD2 interaction. Through its covalent mechanism, MMH1 exhibits sustained BRD4 degradation activity, and shows selective degradation activity for BRD4 BD2 over BRD4 BD1.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 99.83%
- No. CAS: 3079093-16-3
- Fòrmula: C26H29N5O3S
- Peso molecular:491.61
-
Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Actividad biológica
-
Chemical Information
-
Solvente y solubilidad
- Pureza y Documentación
- Referencias
-
Help & FAQs
Actividad biológica
Descripciòn
IC50 & Target
[1]|
BRD4 BD2 |
DCAF16 |
GAK |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| K562 | DC50 |
1 nM
|
Half-maximal BRD4 degradation activity against human K562 cells incubated for 16 h, measured via western blot analysis.
Half-maximal BRD4 degradation activity against human K562 cells incubated for 16 h, measured via western blot analysis.
|
39075252 |
In Vitro
MMH1 (0.001-100 μM) potently promotes formation of the DDB1-DCAF16-BRD4BD2 ternary complex in a recombinant TR-FRET assay, with peak activity at 1 μM, while its non-reactive analog MMH1-NR (HY-157591) does not[1].
MMH1 (1-100 nM; 6 h, 0.1-10 μM; 16 h, 0.1 μM; 4 h pre-treatment followed by 20 h washout) potently degrades BRD4 in K562 cells, with a half-maximal degradation concentration (DC50,16h) of ~1 nM and maximal degradation (D_max,16h) of ~95%, while its non-reactive analog MMH1-NR does not induce BRD4 degradation[1].
MMH1 (1 μM; 4 h) induces a covalent-dependent interaction between GAK14-351 and BRD4_BD2 in 293T cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. .
-
Cell Line:K562 cells
-
Concentration:1, 10, 100 nM (6 h); 0, 0.1, 1, 10 μM (16 h); 0.1 μM (washout pre-treatment)
-
Incubation Time:6 h; 16 h; 4 h pre-treatment followed by 20 h washout
-
Result:Induced visible BRD4 degradation at 10 nM and 100 nM after 6 h, with degradation comparable to heterobifunctional degraders dBET6 and MZ1.
Induced robust BRD4 degradation across 0.1-10 μM after 16 h.
Exhibited sustained BRD4 degradation after washout, maintaining reduced BRD4 levels 20 h after a 4 h pre-treatment with 0.1 μM MMH1.
Achieved a half-maximal degradation concentration (DC50,16h) of 1 nM and maximal degradation (D_max,16h) of 95%.
Chemical Information
-
No. CAS 3079093-16-3
-
Appearance Solid
-
Peso molecular 491.61
-
Fòrmula C26H29N5O3S
-
Color White to off-white
-
SMILES
CC1=C(C)SC2=C1C(C3=CC=C(NC(C=C)=O)C=C3)=N[C@@H](CC(OC(C)(C)C)=O)C4=NN=C(C)N42
-
Envío
Room temperature in continental US; may vary elsewhere.
-
Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (203.41 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (5.09 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 2.5 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.09 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 2.5 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
-
Ficha de datos (295 KB)
-
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
-
Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0341 mL | 10.1707 mL | 20.3413 mL | 50.8533 mL |
| 5 mM | 0.4068 mL | 2.0341 mL | 4.0683 mL | 10.1707 mL | |
| 10 mM | 0.2034 mL | 1.0171 mL | 2.0341 mL | 5.0853 mL | |
| 15 mM | 0.1356 mL | 0.6780 mL | 1.3561 mL | 3.3902 mL | |
| 20 mM | 0.1017 mL | 0.5085 mL | 1.0171 mL | 2.5427 mL | |
| 25 mM | 0.0814 mL | 0.4068 mL | 0.8137 mL | 2.0341 mL | |
| 30 mM | 0.0678 mL | 0.3390 mL | 0.6780 mL | 1.6951 mL | |
| 40 mM | 0.0509 mL | 0.2543 mL | 0.5085 mL | 1.2713 mL | |
| 50 mM | 0.0407 mL | 0.2034 mL | 0.4068 mL | 1.0171 mL | |
| 60 mM | 0.0339 mL | 0.1695 mL | 0.3390 mL | 0.8476 mL | |
| 80 mM | 0.0254 mL | 0.1271 mL | 0.2543 mL | 0.6357 mL | |
| 100 mM | 0.0203 mL | 0.1017 mL | 0.2034 mL | 0.5085 mL |
MMH1 Related Classifications
HY-156827 Related Classifications
Powered by Bioz