2. PROTAC MAPK/ERK Pathway GPCR/G Protein Apoptosis Cell Cycle/DNA Damage
  3. PROTACs Ras Apoptosis PERK p38 MAPK Caspase TNF Receptor
  4. MCB-36

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)).

For research use only. We do not sell to patients.

MCB-36

MCB-36 Chemical Structure

CAS No. : 3104382-00-2

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Customer Review

Based on 1 publication(s) in Google Scholar

MCB-36 Related Antibodies

Top Publications Citing Use of Products

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  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

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))[1].

IC50 & Target[1]

KRas G12C

 

KRas G12D

 

KRas G12V

 

KRAS G13D

 

K-Ras WT

 

Caspase 3

 

In Vitro

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.

MCB-36 Related Antibodies

Western Blot Analysis[1]

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.

Western Blot Analysis[1]

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.

Western Blot Analysis[1]

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.
In Vivo

MCB-294 (10 mg/kg, i.p., single dose) is bioavailable in mice and decreases both KRAS and p-ERK levels 6 h post-treatment[1].
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.
Molecular Weight

1100.32

Formula

C60H71F2N9O7S
CAS No.
Appearance

Solid

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
Shipping

Room temperature in continental US; may vary elsewhere.
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)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 0.9088 mL 4.5441 mL 9.0883 mL
5 mM 0.1818 mL 0.9088 mL 1.8177 mL
View the 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.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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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.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (2.27 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Dosing volume
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Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
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% 
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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

Purity: 98.43%

SDS (251 KB)

COA (254 KB) HNMR (156 KB) RP-HPLC (143 KB) LCMS (388 KB)

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
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
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MCB-36 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

MCB-363104382-00-2MCB36MCB 36PROTACsRasApoptosisPERKp38 MAPKCaspaseTNF ReceptorProtein kinase R-like endoplasmic reticulum kinasePKR-like endoplasmic reticulum kinaseTumor Necrosis Factor ReceptorTNFRKRAS signalingcancer therapeuticsdegraderimmune evasiononcogenic KRASpan-KRAS inhibitortargeted protein degradationtherapy resistancetumor immune microenvironmentInhibitorinhibitorinhibit

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