NST-628

SKU: orb2565643

Description

NST-628 is a pan-RAF molecular glue that stabilizes the RAF-MEK complex to block MEK phosphorylation and activation. This inhibitor is a valuable research tool for studying MAPK/ERK pathway dysregulation in cancer, applicable in both cellular and animal model studies.

Research Area

Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 3002056-30-3
• MW: 488.46
• Purity: 98.86% (May vary between batches)
• Formula: C₂₂H₁₈F₂N₄O₅S
• SMILES: O=C1OC=2C=C(OC3=NC=CC=C3F)C=CC2C(=C1CC=4C=CN=C(NS(=O)(=O)NC)C4F)C
• Target: MEK,Raf,Molecular Glues
• Solubility: DMSO:80 mg/mL (163.78 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (6.76 mM)

Bioactivity

• In Vivo:
  NST-628 when administered orally (p.o.) at doses of 3 mg/kg and 5 mg/kg once daily (qd), or 1.5 mg/kg twice daily (b.i.d), significantly slowed tumor growth in models with KRAS and NRAS mutations. In the SK-MEL-2-luc model, it caused tumor regression. Administered intragastrically (i.g.) at 0.3-3 mg/kg once daily for 18-20 days, NST-628 inhibited the RAS-MAPK pathway in mice in a dose-dependent manner, showing strong anti-tumor activity in the MeWo-luc model. At a dose of 2 mg/kg once daily for 26 days in an NCI-H23 KRASG12C-mutant lung adenocarcinoma model, NST-628 effectively slowed tumor growth and significantly inhibited the RAS-MAPK pathway.
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• In Vitro:
  NST-628 demonstrates elevated antiproliferative activity in BRAF Class II/III mutant cell models compared to other RAF and MEK inhibitors, without promoting heterodimer formation of BRAF and CRAF. NST-628 (4-100 nM; 48 h) induces early and late apoptosis in a dose-dependent manner and decreases live cell populations in NRAS mutant IPC-298 and SK-MEL-2, NF1 mutant MeWo, and KRAS mutant HCT116 cell lines.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

NST 628, NST628, MEK, Raf

Compound Identifiers

PubChem CID

169262739