CZ-415

SKU: orb1226300

Description

A potent, highly selective, ATP-competitive and orally bioavailable mTOR inhibitor with pKd of 8.2; displays >100-fold selectivity over PI3Ks; inhibit downstream targets phosphorylation of pS6RP (S240/244) and pAkt (S473) in HEK293T cells with IC50 of 14.5 nM and 14.8 nM, inhibits IFNγ production in stimulated human whole blood with IC50 of 226 nM; shows efficacy in a semitherapeutic collagen induced arthritis (CIA) mouse model.

Key Properties

• CAS Number: 1429639-50-8
• MW: 459.5618
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₉N₅O₄S
• SMILES: O=C(NCC)NC1=CC=C(C2=NC(N3[C@@H](C)COCC3)=C4C(C(C)(C)S(C4)(=O)=O)=N2)C=C1
• Target: mTOR
• Solubility: DMSO: ≥ 31 mg/mL

Bioactivity

• In Vivo:
  CZ415 is a highly selective mTOR inhibitor showing In vivo efficacy in a collagen induced arthritis (CIA) model. For full characterization of CZ415 and to enable improved dose predictions, the pharmacokinetic (PK) profile is assessed in rat. PK and oral bioavailability are determined after of 1 mg/kg intravenous (iv) bolus and 3 mg/kg oral (po) administration. The observed plasma clearance, corresponding to 45% liver blood flow, suggests that sufficient levels of free compound are circulating in the animal over time. The oral uptake is rapid with a Tmaxmax of 0.5 h and bioavailability F = 44% indicates very good absorption from the gut.
• In Vitro:
  Inhibition of phosphorylation for both downstream targets results in 14.5 nM IC50 for pS6RP and 14.8 nM for pAKT. The immunosuppressive effect of CZ415 is measured by detecting secreted IFNγ after 18 hours in stimulated human whole blood and the resulting IC50 is 226 nM. As a predictor for cardiotoxicity, the activity of CZ415 against the human cardiac ion channel hERG is assessed in a whole-cell patch-clamp assay in HEK293 cells resulting in an IC50 of 48 μM.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CZ415

Quick Database Links

Gene Symbol

mTOR