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

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MCB-36 Related Antibodies

Top Publications Citing Use of Products

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TNFRSF1A/CD120a TNFRSF4 TNFRSF5/CD40 TNFRSF6/Fas/CD95 TNFRSF7/CD27 TNFRSF8/CD30 TNFRSF9/4-1BB/CD137 TNFRSF12A/TWEAK TNFRSF16/NGF Receptor/CD271 TNFRSF18/GITR/CD357

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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 levels, 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
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

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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MCB-36 Related Classifications

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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-36MCB36MCB 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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