Desmethyl Erlotinib hydrochloride

SKU: orb1300610

Description

Desmethyl Erlotinib hydrochloride (OSI-420) is the pharmacologically active metabolite of the EGFR inhibitor erlotinib. It potently inhibits EGFR tyrosine kinase activity and its autophosphorylation, with IC50 values of 2 nM and 20 nM, respectively. This compound is widely used in cancer research for in vitro mechanistic studies and in vivo models of EGFR-driven tumors.

Research Area

Cardiovascular Research, Metabolism Research, Signal Transduction

Key Properties

• CAS Number: 183320-51-6
• MW: 415.87
• Purity: 99.49% (May vary between batches)
• Formula: C₂₁H₂₁N₃O₄·HCl
• SMILES: Cl.COCCOc1cc2ncnc(Nc3cccc(c3)C#C)c2cc1OCCO
• Target: EGFR,Drug Metabolite
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.81 mM);DMSO:77 mg/mL (185.15 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  EGFR:2 nM
• In Vivo:
  At doses of 100 mg/kg, Erlotinib completely prevents EGF-induced autophosphorylation of EGFR in human HN5 tumors growing as xenografts in athymic mice and of the hepatic EGFR of the treated mice. Erlotinib reduces the growth of xenografted human AML cells.
• In Vitro:
  OSI-420 is the major metabolite of Erlotinib in human plasma. Erlotinib disappearance from plasma after a short IV infusion is biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma is 30% (range 12-59%) of erlotinib, and OSI-420 clearance is more than 5-fold higher than erlotinib. Erlotinib and OSI-420 are equipotent, and the combined concentrations of erlotinib + OSI-420 achieved in the CSF exceeded the IC50 (7.9 ng/ml or 20 nM) for the EGFR tyrosine kinase inhibition in intact tumor cells. Erlotinib potently inhibits EGFR activation in intact cells including HNS human head and neck tumor cells (IC50 20 nM), DiFi human colon cancer cells andMDA MB-468 human breast cancer cells. Erlotinib (1 μM) induces apoptosis in DiFi human colon cancer cells. Erlotinib inhibits growth of a panel of NSCLC cell lines including A549, H322, H3255, H358 H661, H1650, H1975, H1299, H596 with IC50 ranging from 29 nM to >20 μM. Erlotinib(2 μM) significantly inhibits growth of AsPC-1 and BxPC-3 pancreatic cells. The effects of Erlotinib HCl in combination with gemcitabine are considered additive in KRAS-mutated pancreatic cancer cells. Ten micromolar of Erlotinib inhibits EGFR phospho-rylation at the Y845 (Src-dependent phosphorylation) and Y1068 (auto-phosphorylation) sites. Combination with Erlotinib could down-modulate rapamycin-stimulated Akt activity and produces a synergistic effect on cell growth inhibition.
• Cell Research:
  Exponentially growing cells are seeded in 96-well plastic plates and exposed to serial dilutions of erlotinib, pemetrexed, or the combination at a constant concentration ratio of 4:1 in triplicates for 72 h. Cell viability is assayed by cell count and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Growth inhibition is expressed as the percentage of surviving cells in drug-treated versus PBS-treated control cells (which is considered as 100% viability). The IC50 value is the concentration resulting in 50% cell growth inhibition by a 72-h exposure to drug(s) compared with untreated control cells and is calculated by the CalcuSyn software. (Only for Reference)

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

CP 473420, CP 373420, CP-373420, CP373420, CP-473420, CP473420, DesMethyl Erlotinib (CP-473420) HCl, Desmethyl Erlotinib hydrochloride, Desmethyl Erlotinib Hydrochloride, Desmethyl Erlotinib, Drug Metabolite, DrugMetabolite, inhibit, OSI420, OSI-420, OSI 420, EGFR, Inhibitor

Compound Identifiers

PubChem CID

18924996