MGCD-265

SKU: orb1223771

Description

MGCD-265 is a potent, multi-target and ATP-competitive inhibitor of c-Met and VEGFR1/2/3 with IC50 of 1 nM, 3 nM/3 nM/4 nM, respectively; also inhibits Ron and Tie2. Phase 1/2.(In Vitro):MGCD-265 analog inhibits A549 cells migration and DU145 cells scattering, with IC50s of 0.4 μM and 0.08 μM, respectively, in HGF-driven cell migration and scattering assays.MGCD-265 analog inhibits HUVEC ERK phosphorylation (IC50=0.03 μM) and HUVEC proliferation (IC50=0.006 μM) in VEGF-dependent cell-based assays.(In Vivo):MGCD-265 analog (20 mg/kg; p.o.) inhibits tumor growth inhibition on various human tumor models in mice.MGCD-265 analog exhibits moderate oral bioavailability (rat 12%, dog 42%) and Cmax (rat 0.14, dog 0.21 uM/(mg/kg)) following oral administration (rat 5-25, dog 5 mg/kg).MGCD-265 analog exhibits reasonable terminal elimination half-lives (rat 1.2, dog 5.8 h) due to plasma clearance (rat 0.33, dog 1.1 L/(kg h)) following intravenous administration (rat 2.5, dog 0.8 mg/kg) .

Key Properties

• CAS Number: 875337-44-3
• MW: 517.6
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₀FN₅O₂S₂
• SMILES: O=C(NC(NC1=CC=C(OC2=C3C(C=C(C4=CN(C)C=N4)S3)=NC=C2)C(F)=C1)=S)CC5=CC=CC=C5
• Target: c-Met/HGFR
• Solubility: DMSO:104 mg/mL (200.92 mM); Ethanol:<1 mg/mL (<1 mM); Water:<1 mg/mL (<1 mM)

Bioactivity

• In Vivo:
  MGCD-265 analog (20 mg/kg; p.o.) inhibits tumor growth inhibition on various human tumor models in mice. MGCD-265 analog exhibits moderate oral bioavailability (rat 12%, dog 42%) and Cmax (rat 0.14, dog 0.21 uM/(mg/kg)) following oral administration (rat 5-25, dog 5 mg/kg). MGCD-265 analog exhibits reasonable terminal elimination half-lives (rat 1.2, dog 5.8 h) due to plasma clearance (rat 0.33, dog 1.1 L/(kg h)) following intravenous administration (rat 2.5, dog 0.8 mg/kg). Animal model: Female Sprague-Dawley rats. Dosage: 2.5 mg/kg for i. v. ; 5-25 mg/kg for oral (Pharmacokinetic Analysis). Administration: Intravenous injection and oral administration. Result: Oral bioavailability (12%), Cmax (0.14 μM/(mg/kg)), T1/2 (1.2 h),. Animal model: Male beagle dogs. Dosage: 0.8 mg/kg for i. v. ; 5 mg/kg for oral (Pharmacokinetic Analysis). Administration: Intravenous administration and oral administration. Result: Oral bioavailability (42%), Cmax (0.21 uM/(mg/kg)), T1/2 (5.8 h).
• In Vitro:
  MGCD-265 analog inhibits A549 cells migration and DU145 cells scattering, with IC50s of 0.4 μM and 0.08 μM, respectively, in HGF-driven cell migration and scattering assays. MGCD-265 analog inhibits HUVEC ERK phosphorylation (IC50 = 0.03 μM) and HUVEC proliferation (IC50 = 0.006 μM) in VEGF-dependent cell-based assays.

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

Glesatinib

Quick Database Links

Gene Symbol

c-Met/HGFR