CEP-40783

SKU: orb1302869

Description

CEP-40783 (RXDX-106) is a potent and selective oral inhibitor of AXL and c-Met kinases, with additional activity against MER and TYRO3. It is utilized in preclinical cancer research to investigate pathways involved in tumor growth, metastasis, and therapeutic resistance in both cellular and animal models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1437321-24-8
• MW: 588.56
• Purity: 99.84% (May vary between batches)
• Formula: C₃₁H₂₆F₂N₄O₆
• SMILES: COc1cc2nccc(Oc3ccc(NC(=O)c4cn(C(C)C)c(=O)n(-c5ccc(F)cc5)c4=O)cc3F)c2cc1OC
• Target: TAM Receptor,c-Met/HGFR
• Solubility: DMSO:5.89 mg/mL (10.01 mM);H2O:Insoluble;Ethanol:2 mg/mL (3.4 mM)

Bioactivity

• Target IC50:
  c-Met:12 nM (Biochemical)|Axl:7 nM (Biochemical)|Mer:29 nM (Biochemical)|Tyro3:19 nM (Biochemical)
• In Vivo:
  CEP-40783 showed dose- and time-dependent inhibition of AXL phosphorylation using NCI-H1299 NSCL xenografts with ～80% target inhibition at 0.3 mg/kg 6 h post dose and complete target inhibition to >90% inhibition at 1 mg/kg between 6-24 h, while a 10 mg/kg po dose resulted in complete AXL inhibition up to 48 h post dosing. In AXL/NIH3T3 xenografts, 0.3 mg/kg po resulted in complete tumor regressions. CEP-40783 was also efficacious in reducing spontaneous lymph node and pulmonary metastatic tumor burden in the MDA-MB-231-luc and 4T1-luc orthotopic breast cancer models, respectively, at 10 and 30 mg/kg po. PK/PD evaluation of the c-Met activity of CEP-40783 (10, 30, 55 mg/kg po qdX5d) showed significant to complete inhibition of c-Met phosphorylation in GTL-16 gastric carcinoma xenografts. Efficacy studies in GTL-16 xenografts demonstrated significant anti-tumor efficacy (tumor stasis and regressions) at 10 and 30 mg/kg po. In EBC-1 NSCL xenografts, administration of CEP-40783 (3, 10 and 30 mg/kg, po qd) resulted in dose-related efficacy, with tumor stasis at 3 mg/kg, tumor regressions and >96% TGI at 10 mg/kg.
• In Vitro:
  In AXL-transfected 293 gT cells, CEP-40783 is 27-fold more active compared to the recombinant enzyme (IC50: 0.26 nM). In GTL-16 cells, CEP-40783 also has superior activity against c-Met (IC50: 6 nM). The enhanced inhibitory activity of CEP-40783 in cells is attributed to its extended residence time on both c-Met and AXL, similar with a Type II mechanism. CEP-40783 shows high kinome selectivity against 298 kinases with an S90 of 0.04 (fraction of kinases showing >90% inhibition at 1 μM).

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

CEP 40783, CEP40783, CEP-40783, cMet, c-Met, c-MET, c-Met/HGFR, cMet/HGFR, AXL, Axl, Inhibitor, HGFR, Mer, inhibit, RXDX106, RXDX-106, RXDX 106, TAMReceptor, TAM Receptor, Tyro3

Compound Identifiers

PubChem CID

71576419