MJP6412
Based on 1 Customer Validation
MJP6412 is a p300 and CBP PROTAC degrader that potently degrades p300 and CBP in 22Rv1 cells with DC50 values of 1.6 nM and 1.2 nM, respectively. MJP6412 downregulates the expression of AR-FL, AR-V7 and c-MYC, as well as androgen receptor target genes (KLK3, FKBP5, TMPRSS2). MJP6412 completely abolishes p300/CBP-dependent histone acetylation (H3K27Ac and H2BNTAC) and induces G1 cell cycle arrest. MJP6412 inhibits cancer cell proliferation and tumor growth. MJP6412 can be used in prostate cancer-related research.
(Pink: CBP/p300 ligand (HY-111784); Blue: Cereblon ligand (HY-W087383); Black: linker (HY-W102095)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 95.90%
- No. CAS: 3105406-14-9
- Fòrmula: C55H54F2N8O9
- Peso molecular:1009.06
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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]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
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p300 |
CBP |
AR-FL |
AR-V7 |
KLK3 |
FKBP5 |
TMPRSS2 |
MJP6412 (0.1-1000 nM; 24 h) potently degrades p300 (DC50 = 1.6 nM, Dmax = 96%) and CBP (DC50 = 1.2 nM, Dmax = 89%) in 22Rv1 human castration-resistant prostate cancer cells after 24 h of treatment[1].
MJP6412 (5 days) potently inhibits the growth of 22Rv1 human castration-resistant prostate cancer cells with an IC50 of 37.6 nM and Imax of 91% after 5 days of treatment[1].
MJP6412 (0.1-1000 nM; 24 h) potently degrades p300 (DC50 = 3.4 nM, Dmax = 94%) and CBP (DC50 = 3.7 nM, Dmax = 82%) in LNCaP human prostate cancer cells after 24 h of treatment[1].
MJP6412 (0.1-1000 nM; 24 h) potently degrades p300 (DC50 = 1.6 nM, Dmax = 97%) and CBP (DC50 = 1.4 nM, Dmax = 89%) in VCaP human prostate cancer cells after 24 h of treatment[1].
MJP6412 (10 nM; 12 h) degrades p300 and CBP in 22Rv1 human castration-resistant prostate cancer cells via a ubiquitin-proteasome-dependent PROTAC mechanism that requires CRBN recruitment and binding to p300/CBP[1].
MJP6412 (100 nM; 6 h) acts as a highly selective p300/CBP degrader in 22Rv1 human castration-resistant prostate cancer cells, with no reduction in known CRBN neo-substrates after 6 h of treatment with 100 nM[1].
MJP6412 (5 days) potently inhibits the growth of VCaP human prostate cancer cells with an IC50 of 7.9 nM and Imax of 98% after 5 days of treatment[1].
MJP6412 (5 days) potently inhibits the growth of LNCaP human prostate cancer cells with an IC50 of 21.4 nM and Imax of 89% after 5 days of treatment[1].
MJP6412 (5 days) potently inhibits the growth of enzalutamide-resistant VCaP-ENR human prostate cancer cells with an IC50 of 5.2 nM and Imax of 98% after 5 days of treatment[1].
MJP6412 (5 days) potently inhibits the growth of enzalutamide-resistant LNCaP-ENR human prostate cancer cells with an IC50 of 138.1 nM and Imax of 72% after 5 days of treatment[1].
MJP6412 (10-100 nM; 24-48 h) downregulates AR and c-MYC signaling in 22Rv1 human castration-resistant prostate cancer cells, reducing AR-FL, AR-V7, and c-MYC protein and mRNA levels, as well as AR-regulated gene mRNA levels, after 24−48 h of treatment with 10−100 nM[1].
MJP6412 (10-100 nM; 12 h) completely extinguishes p300/CBP-dependent histone acetylation (H3K27Ac, H2BK5Ac, H2BK20Ac) in 22Rv1 human castration-resistant prostate cancer cells after 12 h of treatment with 100 nM[1].
MJP6412 (10 nM; 0.25-96 h) induces long-lasting degradation of p300 and CBP in 22Rv1 human castration-resistant prostate cancer cells, with maximum degradation starting at 12 h and lasting through 48 h after treatment with 10 nM[1].
MJP6412 (1-100 nM; 48 h) induces dose-dependent G1 cell cycle arrest in VCaP human prostate cancer cells, with significant arrest occurring after 48 h of treatment with 100 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:VCaP human prostate cancer cells
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Concentration:1, 10 and 100 nM
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Incubation Time:48 h
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Result:Induced G1 cell cycle arrest in a dose-dependent manner.
Induced detectable G1 arrest at 1 nM.
Significantly induced G1 arrest at 100 nM.
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Cell Line:VCaP cells
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Concentration:0.1, 1, 10 and 100 nM
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Incubation Time:24 h (for AR-FL, AR-V7, and c-MYC protein expression); 12 h (for H2BK5Ac, H2BK20Ac, and H3K27Ac protein expression)
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Result:Treatment with 0.1, 1, 10, and 100 nM for 24 h resulted in a dose-dependent decrease in AR-FL, AR-V7, and c-MYC protein expression.
At 10 nM, the expression of AR-FL and AR-V7 was significantly reduced, and at 100 nM, a >80% reduction in AR-FL and AR-V7 proteins was observed.
For c-MYC, 10 nM significantly reduced its expression, and 100 nM almost completely depleted it.
In the acetylation assay, treatment with 10 nM for 12 h significantly decreased the levels of H3K27Ac, H2BK5Ac, and H2BK20Ac, and these acetylation marks were almost completely abolished at 100 nM.
| Species | Dose | Route | T1/2 | AUC0-t | Vz | CL | MRT0-t |
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| Mice[1] | 5 mg/kg | i.v. | 4.27 h | 2407 ng/mL·h | 12500 mL/kg | 2058 mL/h/kg | 2.75 h |
MJP6412 (3-15 mg/kg; i.v.; every other day; 24 days) exhibits significant antitumor activity with a 42% TGI in VCaP prostate cancer xenograft tumors in BALB/c-Nude mice, with excellent biosafety[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR mice 22Rv1 prostate cancer xenograft[1]
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Dosage:10 mg/kg
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Administration:i.p.; single dose
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Result:Reduced p300 protein levels in 22Rv1 xenograft tumor tissue at 6 hours post-treatment.
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Animal Model:Male BALB/c-Nude mice, 6 weeks old, were maintained in a standard SPF mouse room. VCaP cells (1 × 10⁷ cells in Matrigel (Corning Life Sciences), 0.2 mL/mouse) were injected subcutaneously into the right side of the induced cell-derived xenograft tumor and allowed to grow to the indicated size. When the average volume of the tumors reached approximately 200 mm³, treatment can start.
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Dosage:3 mg/kg; 15 mg/kg
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Administration:i.v.; every other day; 24 days
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Result:Achieved a tumor growth inhibition (TGI) value of 42% at 15 mg/kg, comparable to positive control CCS1477.
Was well tolerated, with no significant mouse weight loss observed over the 24-day treatment period.
Chemical Information
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No. CAS 3105406-14-9
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Appearance Solid
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Peso molecular 1009.06
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Fòrmula C55H54F2N8O9
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Color Light yellow to yellow
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SMILES
O=C(CCC1N(C(C2=C3C=CC(N4CCC(CC4)OC5=CC=C(C=C5)NC(CO[C@H]6CC[C@H](N7C([C@H]8N(C9=CC(F)=C(F)C=C9)C(CCC8)=O)=NC%10=CC(C%11=C(C)ON=C%11C)=CC=C7%10)CC6)=O)=C2)=O)C3=O)NC1=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 100 mg/mL (99.10 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)
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 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.48 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2.5 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
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.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%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
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Ficha de datos (282 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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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 |
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| DMSO | 1 mM | 0.9910 mL | 4.9551 mL | 9.9102 mL | 24.7755 mL |
| 5 mM | 0.1982 mL | 0.9910 mL | 1.9820 mL | 4.9551 mL | |
| 10 mM | 0.0991 mL | 0.4955 mL | 0.9910 mL | 2.4776 mL | |
| 15 mM | 0.0661 mL | 0.3303 mL | 0.6607 mL | 1.6517 mL | |
| 20 mM | 0.0496 mL | 0.2478 mL | 0.4955 mL | 1.2388 mL | |
| 25 mM | 0.0396 mL | 0.1982 mL | 0.3964 mL | 0.9910 mL | |
| 30 mM | 0.0330 mL | 0.1652 mL | 0.3303 mL | 0.8259 mL | |
| 40 mM | 0.0248 mL | 0.1239 mL | 0.2478 mL | 0.6194 mL | |
| 50 mM | 0.0198 mL | 0.0991 mL | 0.1982 mL | 0.4955 mL | |
| 60 mM | 0.0165 mL | 0.0826 mL | 0.1652 mL | 0.4129 mL | |
| 80 mM | 0.0124 mL | 0.0619 mL | 0.1239 mL | 0.3097 mL |
MJP6412 Related Classifications
HY-168201 Related Classifications
Powered by Bioz
- MJP6412
- 3105406-14-9
- MJP 6412
- MJP-6412
- PROTACs
- Histone Acetyltransferase
- c-Myc
- Androgen Receptor
- CRBN
- p300
- LNCaP human prostate cancer cells
- ubiquitin proteasome system
- enzalutamide-resistant prostate cancer
- CBP
- androgen receptor
- VCaP human prostate cancer cells
- xenograft model
- 22Rv1 human castration-resistant prostate cancer cells
- Inhibitor
- inhibitor
- inhibit