MCB-36
Based on 1 Customer Validation
MCB-36 is a pan-KRAS PROTAC degrader that recruits VHL, with a Kd value of approximately 1 pM against KRAS, and it does not affect KRAS transcription. MCB-36 continuously degrades various KRAS mutants, inhibits oncogenic KRAS signaling pathways, reduces p-ERK levels, and induces apoptosis, thereby suppressing the growth of KRAS-dependent cancer cells. In vivo, MCB-36 inhibits tumor growth, overcomes resistance to KRAS G12C inhibitors, remodels the tumor immune microenvironment and enhances immune cell infiltration. MCB-36 can be used in research related to colorectal cancer and lung cancer.
(Pink: Target protein ligand; Blue: VHL ligand (HY-112078); Black: linker (HY-W091879)).
For research use only. We do not sell to patients.
- Purity : 98.43%
- CAS No.: 3104382-00-2
- Formula: C60H71F2N9O7S
- Molecular Weight:1100.32
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Storage: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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
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KRas G12C |
KRas G12D |
KRas G12V |
KRAS G13D |
K-Ras WT |
Caspase 3 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| MIA PaCa-2 | IC50 |
131.10 nM
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Inhibition of cell viability against parental MIA PaCa-2 human cancer cells incubated for 5 days via 2D cell viability assay.
Inhibition of cell viability against parental MIA PaCa-2 human cancer cells incubated for 5 days via 2D cell viability assay.
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40780213 |
In Vitro
MCB-36 (0.3125-5 nM; 120 s association, 300 s dissociation) binds to GDP-bound KRASG12D, KRASG12C, KRASG12V, and wild-type proteins with high affinity (Kd ≈ 1 pM) in cell-free SPR assays[1].
MCB-36 (100 nM; 12 h) significantly reduces the abundance of KRAS protein in AsPC-1 and H358 human cancer cells[1].
MCB-36 (0-10 μM; 3-48 h) induces concentration- and time-dependent degradation of KRAS and shortens the half-life of KRAS protein in human cancer cell lines AsPC-1, H358, Capan-2 and Caco-2[1].
MCB-36 (12 h) potently degrades wild-type and multiple mutant KRAS variants (KRASG12D, KRASG12C, KRASG12V, KRASG12S, KRASG13D, KRASQ61H) in transfected 293T cells[1].
MCB-36 forms a cooperative ternary complex with purified VCB, KRASG12D or KRASG12C proteins in cell-free fluorescence polarization (FP) assays[1].
MCB-36 forms a ternary complex with purified VCB and KRAS proteins in cell-free HTRF assays[1].
MCB-36 induces the formation of an intracellular ternary complex between KRAS and VHL in transfected 293T cells[1].
MCB-36 (administered for 5 consecutive days) inhibits the growth of KRAS-dependent human cancer cells with a mean IC50 of approximately 1 μM, whereas it exerts no significant inhibitory effect on KRAS-independent cancer cells and normal human cells (IC50 >10 μM)[1].
MCB-36 (administered for 5 consecutive days) inhibits the growth of MIA PaCa-2/SR and MIA PaCa-2/AR cells that are resistant to KRASG12C inhibitors, with IC50 values of 319.10 nM and 438.60 nM respectively after 5 days of treatment[1].
MCB-36 (administered for 5 consecutive days) inhibits the growth of MIA PaCa-2 cells harboring KRASG12C/Y96C or KRASG12C/H95D second-site mutations, with IC50 values of 186.50 nM and 185.70 nM respectively after 5 days of treatment, and retains activity against these KRASG12C inhibitor-resistant mutants[1].
MCB-36 (0-10 μM; 3-48 h) induces concentration- and time-dependent inhibition of KRAS signaling (decreased p-ERK levels) and apoptosis (increased levels of activated caspase-3 and activated PARP) in KRAS-dependent human cancer cells[1].
MCB-36 (0.3-0.6 μM; 6 days) inhibits the growth of patient-derived organoids from human colorectal cancer with KRAS mutations, while suppressing the MAPK signaling pathway and inducing apoptosis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KRAS-mutant colorectal cancer organoids
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Concentration:0, 1.25 and 2.5 μM
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Incubation Time:6 days
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Result:Decreased p-ERK, cleaved caspase-3, and cleaved PARP.
In Vivo
MCB-36 (60 mg/kg; i.p.; twice daily; for 16 consecutive days) exhibits potent antitumor activity in KRASG12V-mutant lung cancer PDX models, reduces tumor volume and weight, and downregulates the expression levels of KRAS and Ki67[1].
MCB-36 improves survival outcomes in a genetically engineered mouse model of pancreatic cancer driven by KRASG12D, extending the median survival to 58 days[1].
MCB-36 can remodel the tumor immune microenvironment in syngeneic CT26 tumors, increasing effector CD8+ T cells and reducing exhausted CD8+ T cells[1].
MCB-36 (60 mg/kg; i.p.; twice daily; 12 or 21 days) acts as a monotherapy to inhibit the growth of syngeneic CT26 tumors, and enhances the efficacy of combination therapy with anti-PD-1 antibody (HY-P990169) without inducing obvious toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (6-8-week-old male)[1]
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Dosage:60 mg/kg
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Administration:i.p.; twice daily; 16 days
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Result:Significantly reduced tumor volume and tumor weight compared to vehicle control.
Decreased KRAS and Ki67 expression in treated tumors.
Maintained sustained tumor growth inhibition following 16 days of treatment and a 12-day treatment-free period.
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Animal Model:BALB/c nude mice (6-8-week-old male)[1]
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Dosage:60 mg/kg
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Administration:i.p.; twice daily; 16 days
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Result:Significantly reduced tumor volume and tumor weight compared to vehicle control.
Decreased KRAS and Ki67 expression in treated tumors.
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Animal Model:BALB/c mice (4-5-week-old male)[1]
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Dosage:60 mg/kg (monotherapy); 60 mg/kg + 25 μg/dose (combination with anti-PD-1 antibody (HY-P990169))
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Administration:i.p.; twice daily; 12 or 21 days (monotherapy); i.p.; twice weekly (anti-PD-1 antibody component)
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Result:Significantly suppressed tumor growth compared to vehicle control as monotherapy.
Enhanced tumor growth suppression compared to either single agent alone when combined with anti-PD-1 antibody.
Caused no significant body weight loss in treated mice.
Chemical Information
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CAS No. 3104382-00-2
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Appearance Solid
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Molecular Weight 1100.32
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Formula C60H71F2N9O7S
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Color Off-white to yellow
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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
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
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)
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.
In Vivo Dissolution Calculator
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.
Purity & Documentation
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Data Sheet (295 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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Handling Instructions (2659 KB)
References
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 | 0.9088 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
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