AD80

SKU: orb1302971

Description

AD80 is a multikinase inhibitor targeting RET, RAF, SRC, and S6K, while exhibiting minimal activity against mTOR. It is utilized in cancer research for investigating signaling pathways and has demonstrated efficacy in both cellular assays and in vivo tumor models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1384071-99-1
• MW: 473.43
• Purity: 99.9%
• Formula: C₂₂H₁₉F₄N₇O
• SMILES: CC(C)n1nc(-c2ccc(NC(=O)Nc3cc(ccc3F)C(F)(F)F)cc2)c2c(N)ncnc12
• Target: Src,Raf,c-RET,S6 Kinase
• Solubility: DMSO:60 mg/mL (126.73 mM);10% DMSO+40% PEG300+5% Tween-80+45% Saline:1 mg/mL (2.11 mM)

Bioactivity

• Target IC50:
  RET (V804L):0.6 nM|RET (V804M):0.4 nM
• In Vivo:
  AD80 significantly improves survival rates, rescuing 50% of mice transplanted with PTEN-deficient leukemia cells. When administered orally, both AD80 and AD81 remarkably allow 70-90% of Drosophila ptc>dRetMEN2B model animals to reach adulthood, surpassing the effectiveness of AD57. Furthermore, AD80 demonstrates superior tumor growth inhibition and minimizes body-weight fluctuations compared to vandetanib in a mouse xenograft model.
• In Vitro:
  AD80 and AD81 effectively inhibit key signaling molecules (RET, RAF, SRC, S6K) with significantly diminished mTOR activity compared to AD57 and AD58. Specifically, AD80 stands out for its proficient inhibition of the Ras–Erk pathway, showcasing a well-balanced polypharmacological profile that targets Ret, Raf, Src, Tor, and S6K, yielding high efficacy with minimal toxicity. Furthermore, AD80 demonstrates potent anti-proliferative effects on MZ-CRC-1 and TT thyroid cancer cells in vitro, likely mediated by triggering apoptosis. Additionally, AD80 uniquely suppresses S6K1 in conjunction with inhibiting the TAM family tyrosine kinase AXL, preventing S6K1 phosphorylation and its association with mTOR. This leads to a sustained inhibition of S6K1-driven signaling and protein synthesis, underscoring its therapeutic potential.
• Cell Research:
  MZ-CRC-1 (MEN2B) and TT (MEN2A) cells are treated with AD80 (0.2 nM to 20 μM) for 7 days and cell viability is quantitated by MTT assay.
• Animal Research:
  Mice showing established growing tumors are separated into vehicle or drug treatment groups. A similar range of tumor sizes is selected for each experiment (vehicle vs AD57; vehicle vs AD80 vs Vandetanib). Vehicle, AD57 (20 mg/kg), AD80 (30 mg/kg), or Vandetanib (50 mg/kg) are administered by oral gavage (PO; per os or by mouth) once daily, five times a week. Tumor and body weight measurements are performed 3 times a week.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Raf kinases, Raf, Src, S6 Kinase, S6K, S6Kinase, Ribosomal S6 Kinase (RSK), RET, RET V804L, RET V804M, inhibit, Inhibitor, AD80, AD-80, AD 80, cRET

Compound Identifiers

PubChem CID

71578106