TAK-580

SKU: orb1300368

Description

TAK-580 (MLN2480) is an investigational small molecule that potently and selectively inhibits all Raf kinase isoforms. It has been utilized in preclinical research to study oncogenic signaling pathways, demonstrating activity in both in vitro cellular assays and in vivo tumor models relevant to cancer research.

Research Area

Epigenetics & Chromatin, Signal Transduction

Key Properties

• CAS Number: 1096708-71-2
• MW: 506.29
• Purity: 98.42% (May vary between batches)
• Formula: C₁₇H₁₂Cl₂F₃N₇O₂S
• SMILES: CC(NC(=O)c1ncnc(N)c1Cl)c1ncc(s1)C(=O)Nc1cc(c(Cl)cn1)C(F)(F)F
• Target: Raf
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:1 mg/mL (1.98 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:93 mg/mL (183.69 mM);Ethanol:93 mg/mL (183.69 mM)

Bioactivity

• In Vivo:
  In vivo, TAK-580 shows antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models.MLN-2480 (37.5 mg/kg) is well tolerated in a tumor xenograft model. The combination of MLN-2480 (12.5 mg) and TAK-733 (1 mg/kg) is effective in an SK-MEL-30 xenograft model, but monotherapy with either compound produces negligible effects.
• In Vitro:
  TAK-580 inhibits MAPK pathway signaling in BRAF mutant and some RAS mutant preClinicalal cancer models at concentrations that are tolerated in vivo. It is found to activate phosphorylated MEK at very low concentrations, but inhibits this same activity at higher concentrations. The inhibitory effects of MLN-2480 are found to vary across models and genetic contexts. In vitro analysis of this drug combination of TAK-580 and TAK-733(an investigational allosteric MEK kinase inhibitor) in cell proliferation assays demonstrates synergistic activity. In addition, western blot analysis demonstrates the effect of TAK-580 in reversing feedback activation of MEK in response to TAK-733, leading to more concerted MAPK pathway inhibition.MLN-2480 only modestly inhibits PRAK.
• Animal Research:
  Animal Models: C57BL/6J miceFormulation: 100% PEG400Dosages: 12.5 mg/kgAdministration: oral gavage

Storage & Handling

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

Alternative Names

BIIB 024, BIIB024, BIIB-024, Inhibitor, inhibit, MLN 2480, MLN2480, MLN-2480, Raf kinases, Raf, TAK580, TAK-580, TAK 580, Tovorafenib

Compound Identifiers

PubChem CID

57569468