MCB-36
Based on 1 Customer Validation
MCB-36 is a VHL-recruiting pan-KRAS PROTAC degrader without affecting KRAS transcription. MCB-36 exhibits minimal effects on HRAS and NRAS protein levels. MCB-36 binds to the GDP-loaded state of G12D, G12C, G12V, and wild-type KRAS with high affinities Kd ≈ 1 pM). MCB-36 decreases p-ERK levels, leading to cell apoptosis. MCB-36 effectively suppress KRASG12C inhibitor-resistant cancer cells and remodel the tumor immune microenvironment. MCB-36 can be used for the study of colorectal cancer and lung cancer (Pink: Target protein ligand; Blue: E3 ligand (HY-112078); Black: Linker (HY-W091879)).
(Pink: Target protein ligand; Blue: VHL ligand (HY-112078); Black: linker (HY-W091879)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.43%
- No. CAS: 3104382-00-2
- Fòrmula: C60H71F2N9O7S
- Peso molecular:1100.32
-
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
Ver todos los productos específicos de isoformas PROTACs
MoreVer todos los productos específicos de isoformas Caspase
MoreVer todos los productos específicos de isoformas TNF Receptor
More
Actividad biológica
|
KRas G12C |
KRas G12D |
KRas G12V |
KRAS G13D |
K-Ras WT |
Caspase 3 |
MCB-36 (1 nM-100 μM, 5 days) shows significant anti-proliferative effects on KRAS-dependent cancer cells that rely on KRAS (as PC-1 (G12D), H358 (G12C), LS180 (G12V), HCT116 (G13D), etc.) for growth and survival (24 of 30 cell lines tested with a mean IC50 of around 1 μM) while sparing normal cells (hTERT-HPNE, NCM460) and KRAS-independent cells (IC50 > 10 μM)[1].
MCB-36 (0-10 μM, 0-72 h) effectively degraded KRAS protein, decreased p-ERK levels and induced cell death in all cell lines tested including MIA PaCa-2 cells expressing KRASG12C, KRASG12C/Y96C, and KRASG12C/H95D[1].
MCB-36 (0-2.5 μM, 6 days) suppresses the growth of KRAS-mutant colorectal cancer organoids, accompanied by reduced abundance of MAPK signaling components and reciprocal induction of apoptotic markers.
MCB-36 significantly upregulates the interferon-alpha response pathway in CD45+ immune cells isolated from CT26 tumors and increases the abundance of effector CD8+ T cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:Caco-2 (WT), Capan-2 (G12V), H358 (G12C), AsPC-1 (G12D) cells
-
Concentration:0, 0.1, 1 and 10 μM
-
Incubation Time:0, 3, 6, 12, 24, 48 h
-
Result:Dose- and time- dependently degraded KRAS.
Dose- and time- dependently decreased p-ERK, cleaved caspase-3, and cleaved PARP.
-
Cell Line:MIA PaCa-2 (G12C), MIA PaCa-2 (G12C/Y96C) and MIA PaCa-2 (G12C/H95D)
-
Concentration:100 nM
-
Incubation Time:0, 1, 3, 6, 12, 24, 36, 48, 72 h
-
Result:Inhibited p-ERK level, induced cell death and retained their potency over at least 36 h.
-
Cell Line:KRAS-mutant colorectal cancer organoids
-
Concentration:0, 1.25 and 2.5 μM
-
Incubation Time:6 days
-
Result:Decreased p-ERK, cleaved caspase-3, and cleaved PARP.
MCB-294 (60 mg/kg, i.p., twice daily for 1-21 days) effectively suppresses KRASG12C inhibitor-resistant cancer cells and remodel the tumor immune microenvironment in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Patient-derived xenograft (PDX) model induced by colorectal carcinoma harboring a KRASG12C mutation (PDX A02), and lung adenocarcinoma harboring a KRASG12V mutation (PDX A03) established in four- to five-week-old male BALB/c mice[1]
-
Dosage:60 mg/kg
-
Administration:Intraperitoneal administration (i.p.), twice daily, for 16 days
-
Result:Significantly reduced tumor volume and weight in the PDX A02 and PDX A03 xenograft models.
Showed a dramatic decrease in KRAS and Ki67 expression from a cohort of treated mice.
No signs of overt toxicity were observed, as mouse body weight maintained stable.
-
Animal Model:CT26 induced immunoregulation model established in six- to eight-week-old male BALB/c nude mice[1]
-
Dosage:60 mg/kg
-
Administration:Intraperitoneal administration (i.p.), twice daily, for 2 days
-
Result:Increased the abundance of effector CD8+ T cells, IFN-γ, TNF-α and Ki67.
Enhanced the efficacy of anti-PD-1 therapy.
Chemical Information
-
No. CAS 3104382-00-2
-
Appearance Solid
-
Peso molecular 1100.32
-
Fòrmula C60H71F2N9O7S
-
Color Off-white to yellow
-
SMILES
C#CC1=C(C=CC2=CC(O)=CC(C3=NC=C4C(N5CCC[C@@](O)(C5)C)=NC(OC[C@@H]6CCCN6CCCCCCC(N[C@@H](C(C)(C)C)C(N7C[C@@H](C[C@H]7C(N[C@H](C8=CC=C(C=C8)C9=C(N=CS9)C)C)=O)O)=O)=O)=NC4=C3F)=C21)F
-
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
DMSO : 100 mg/mL (90.88 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.
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 (283 KB)
-
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)
-
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 | 0.9088 mL | 4.5441 mL | 9.0883 mL | 22.7207 mL |
| 5 mM | 0.1818 mL | 0.9088 mL | 1.8177 mL | 4.5441 mL | |
| 10 mM | 0.0909 mL | 0.4544 mL | 0.9088 mL | 2.2721 mL | |
| 15 mM | 0.0606 mL | 0.3029 mL | 0.6059 mL | 1.5147 mL | |
| 20 mM | 0.0454 mL | 0.2272 mL | 0.4544 mL | 1.1360 mL | |
| 25 mM | 0.0364 mL | 0.1818 mL | 0.3635 mL | 0.9088 mL | |
| 30 mM | 0.0303 mL | 0.1515 mL | 0.3029 mL | 0.7574 mL | |
| 40 mM | 0.0227 mL | 0.1136 mL | 0.2272 mL | 0.5680 mL | |
| 50 mM | 0.0182 mL | 0.0909 mL | 0.1818 mL | 0.4544 mL | |
| 60 mM | 0.0151 mL | 0.0757 mL | 0.1515 mL | 0.3787 mL | |
| 80 mM | 0.0114 mL | 0.0568 mL | 0.1136 mL | 0.2840 mL |
MCB-36 Related Classifications
HY-176786 Related Classifications
Powered by Bioz