MCB-294
Based on 1 Customer Validation
MCB-294 is a dual-state pan-KRAS inhibitor that selectively inhibits KRAS over NRAS and HRAS. MCB-294 capable of binding both the active (GTP-bound) and inactive (GDP-bound) forms of KRAS with Kds of approximately 1 pM and 10 nM, respectively. MCB-294 broadly impairs the growth of hTERT-HPNE cells expressing G12D, G12C, G12V, G12S, G13D, and wild-type KRAS, with IC50s of approximately 700 nM. MCB-294 induces irreversible apoptosis in KRAS-mutated tumors. MCB-294 effectively suppress KRASG12C inhibitor-resistant cancer cells and remodel the tumor immune microenvironment. MCB-294 can be used for the study of pancreatic cancer, colorectal cancer and lung cancer.
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- Pureté: 98.04%
- Formule: C34H29D2F4N5O3
- Masse moléculaire:635.65
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Stockage:
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
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KRas G12C |
KRas G12D |
KRas G12V |
KRAS G13D |
K-Ras WT |
Caspase 3 |
MCB-294 inhibits the binding of SOScat to KRAS proteins and disrupted RAF-RBD peptide binding to active KRAS with IC50 values approximately ranging from 1 to 70 nM and from 20 to 150 nM[1].
MCB-294 (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 125 nM) while sparing normal cells (hTERT-HPNE, NCM460) (IC50 > 10 μM)[1].
MCB-294 (0-100 nM, 0-72 h) causes a dose-dependent reduction in p-ERK levels, persistently inhibits components of the MAPK signaling pathway (p-ERK, DUSP6, and cyclin D1) and induces apoptosis markers (CC3 and cPARP) in AsPC-1 and H358 tumors in all tested KRAS-dependent cancer cells including MIA PaCa-2 cells expressing KRASG12C, KRASG12C/Y96C, and KRASG12C/H95D[1].
MCB-294 downregulates pro-survival genes (BIRC5, MCL1, and BCL2L1), upregulates pro-apoptotic genes (BBC3, BCL2L11, and BMF) and decreases KRAS-regulated genes such as CCND1, DUSP6, ETV4, SPRY2, and PHLDA1[1].
MCB-294 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.
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Cell Line:AsPC-1 and H358 cells
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Concentration:0, 10, 30 and 100 nM
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Incubation Time:0, 3, 6, 12, 24 h
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Result:Induced apoptosis markers (CC3 and cPARP) as early as 6 h post-treatment, with effects sustained for 24 h in KRAS-dependent cancer cells.
Preferentially traped KRAS in an inactive state.
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Cell Line:MIA PaCa-2 (G12C), MIA PaCa-2 (G12C/Y96C) and MIA PaCa-2 (G12C/H95D)
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Concentration:30 nM
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Incubation Time:0, 1, 3, 6, 12, 24, 36, 48, 72 h
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Result:Inhibited p-ERK levels, induced cell death and retained their potency over at least 36 h.
MCB-294 (30 mg/kg, i.p., twice daily for 1-16 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.
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Animal Model:AsPC-1/H358 induced xenograft model established in six- to eight-week-old male BALB/c nude mice[1]
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Dosage:30 mg/kg
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Administration:Intraperitoneal administration (i.p.), twice daily, for 1 or 7 days
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Result:Observed p-ERK levels accompanied by reduced plasma drug concentration at 6 h post-treatment under the 1-day dosing regimen, sustained p-ERK suppression was achieved with continuous 7-day dosing.
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Animal Model:Patient-derived xenograft (PDX) model induced by pancreatic ductal adenocarcinoma harboring a KRASG12D mutation (PDX A01), 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]
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Dosage:30 mg/kg
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Administration:Intraperitoneal administration (i.p.), twice daily, for 16 days
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Result:Inhibited tumor growth and maintained the inhibitory effect even after discontinuation of the medication.
Decreased p-ERK and Ki67 levels and increased caspase 3 activity.
No abnormalities in the heart, liver, spleen, lungs, or kidneys and significant weight loss.
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Animal Model:CT26 induced immunoregulation model established in six- to eight-week-old male BALB/c nude mice[1]
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Dosage:30 mg/kg
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Administration:Intraperitoneal administration (i.p.), twice daily, for 2 days
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Result:Increased the abundance of effector CD8+ T cells, IFN-γ, TNF-α and Ki67.
Enhanced the efficacy of anti-PD-1 therapy.
1. This compound can be used as a tracer
2. This compound can be used as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS.
Chemical Information
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Appearance Solid
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Masse moléculaire 635.65
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Formule C34H29D2F4N5O3
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Color Light yellow to yellow
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SMILES
O[C@](C1)(C)CCCN1C2=NC(OC([2H])([2H])C3(CCC4)N4C/C(C3)=C(F)/F)=NC5=C(F)C(C6=C(C(C#C)=C(F)C=C7)C7=CC(O)=C6)=NC=C52
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvant et solubilité
DMSO : ≥ 86 mg/mL (135.29 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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 (sealed storage, away from moisture and light). 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 (sealed storage, away from moisture and light). 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)
Pureté et documentation
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Fiche technique (283 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
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 (sealed storage, away from moisture and light). 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 | 1.5732 mL | 7.8660 mL | 15.7319 mL | 39.3298 mL |
| 5 mM | 0.3146 mL | 1.5732 mL | 3.1464 mL | 7.8660 mL | |
| 10 mM | 0.1573 mL | 0.7866 mL | 1.5732 mL | 3.9330 mL | |
| 15 mM | 0.1049 mL | 0.5244 mL | 1.0488 mL | 2.6220 mL | |
| 20 mM | 0.0787 mL | 0.3933 mL | 0.7866 mL | 1.9665 mL | |
| 25 mM | 0.0629 mL | 0.3146 mL | 0.6293 mL | 1.5732 mL | |
| 30 mM | 0.0524 mL | 0.2622 mL | 0.5244 mL | 1.3110 mL | |
| 40 mM | 0.0393 mL | 0.1966 mL | 0.3933 mL | 0.9832 mL | |
| 50 mM | 0.0315 mL | 0.1573 mL | 0.3146 mL | 0.7866 mL | |
| 60 mM | 0.0262 mL | 0.1311 mL | 0.2622 mL | 0.6555 mL | |
| 80 mM | 0.0197 mL | 0.0983 mL | 0.1966 mL | 0.4916 mL | |
| 100 mM | 0.0157 mL | 0.0787 mL | 0.1573 mL | 0.3933 mL |
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