Erlotinib

SKU: orb1310678

Description

Erlotinib (CP-358774) is a first-generation, ATP-competitive inhibitor targeting EGFR mutants like exon 19 deletions and L858R. It is widely used in preclinical in vitro and in vivo studies of non-small cell lung cancer, though its application can lead to the acquisition of the C797S resistance mutation.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 183321-74-6
• MW: 393.44
• Purity: 99.94%
• Formula: C₂₂H₂₃N₃O₄
• SMILES: N(C=1C2=C(C=C(OCCOC)C(OCCOC)=C2)N=CN1)C3=CC(C#C)=CC=C3
• Target: EGFR,Autophagy
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:7.2 mg/mL (18.3 mM);DMSO:255 mg/mL (648.13 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:12 mg/mL (30.5 mM)

Bioactivity

• Target IC50:
  H1975 cells (L858R + T790M):9.183 μM|HCC827 cells (exon 19 deletion):0.002142 μM|H3255 cells (L858R):0.08898 μM|PC9 cells (exon 19 deletion):0.03136 μM|EGFR:2 nM (cell free)|JAK2 (V617F):4 μM
• In Vivo:
  Erlotinib (20 mg/kg, p.o.) significantly attenuates Cisplatin (CP)-induced body weight (BW) loss when compared to the CP+vehicle (V) rats (P<0.05). Erlotinib treatment significantly improves renal function in CP-N(normal control group, NC) rats. The CP+Erlotinib (E) rats show significant reduction of the levels of Serum creatinine (s-Cr) (P<0.05), blood urea nitrogen (BUN) (P<0.05), urinary N-acetyl-β-D-glucosaminidase (NAG) index (P<0.05), and significant increase of urine volume (UV) (P<0.05) and Cr clearance (Ccr) (P<0.05) compare to the CP+V rats . Erlotinib inhibits tumor growth in human head and neck carcinoma HN5 tumor xenografts in mice with an ED50 value of 9 mg/kg .
• In Vitro:
  Erlotinib is a direct-acting inhibitor of human EGFR tyrosine kinase with an IC50 of 2 nM and reduces EGFR autophosphorylation in intact tumor cells with an IC50 of 20 nM. Erlotinib is also a potent inhibitor of the recombinant intracellular (kinase) domain of the EGFR (IC50: 1 nM). The proliferation of DiFi cells is strongly inhibited by Erlotinib with an IC50 of 100 nM for an 8-day proliferation assay.
• Cell Research:
  Exponentially growing cells are seeded in 96-well plastic plates and exposed to serial dilutions of erlotinib (30 nM-20 μM), 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 the drug(s) compared with untreated control cells and is calculated by the CalcuSyn software .
• Animal Research:
  Six-week-old male SD rats weighing 180 to 210 g are used. Cisplatin (CP) is freshly prepared in saline at a concentration of 1 mg/mL and then injected intraperitoneally in SD rats (n=28) at a dose of 7 mg/kg on day 0. To investigate the effect of Erlotinib, 28 CP-N rats are divided into two groups. Separate groups (n=14) each of animals are administered with either Erlotinib (20 mg/kg) (CP+E, n=14) or vehicle (CP+V, n=14) daily by oral gavage from the day -1 (24 hours prior to the CP injection) to day 3. Vehicle-treated groups receive an equivalent volume of saline. Five male SD rats at the age of 6 weeks are used as a normal control group (NC, n=5). The NC rats are given an equivalent volume of saline daily by oral gavage from the day -1 to day 3. At day 4 (96 hours after CP injection), each rat is anesthetized and sacrificed by exsanguination after the cardiac puncture; blood is collected by cardiac puncture and kidneys are collected. Renal tissue is divided; separate portions are snap-frozen in liquid nitrogen or fixed in 2% paraformaldehyde/phosphate-buffered saline (PBS) for later use. All surgery is performed under diethyl ether gas anesthesia, and all efforts are made to minimize suffering .

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

R1415, R-1415, R 1415, tumor, cell, CP358774, CP-358774, CP 358774, directly, autophosphorylation, Autophagy, cancer, acting, EGFR, Epidermal growth factor receptor, ErbB-1, Erlotinib, Inhibitor, HER1, intact, inhibit, non-small, NSC718781, NSC-718781, OSI744, OSI-744, OSI774, OSI-774, OSI 744, OSI 774, NSC 718781, lung

Compound Identifiers

PubChem CID

176870