Erlotinib

Erlotinib (CP-358774) is a selective, orally active EGFR tyrosine kinase inhibitor. Erlotinib also acts as a substrate and inhibitor of OATP2B1, with an IC₅₀ of approximately 0.079 μM for inhibiting OATP2B1-mediated uptake of estrone 3-sulfate. Erlotinib blocks EGFR phosphorylation, downstream signal transduction, as well as the growth and proliferation of cancer cells. Erlotinib inhibits MMP-10-mediated renal injury, fibrotic lesions, the ERK1/2, GSK-3β and β-catenin signaling pathways, fibronectin, α-SMA, collagen deposition, and renal injury markers. Erlotinib is metabolized via CYP3A to produce the active metabolite OSI-420. Erlotinib can be used in research related to non-small cell lung cancer, gastric cancer, papillary renal cell carcinoma, pancreatic cancer, renal fibrosis, and other conditions^{[1][2][3][4][5]}. In Vitro:Erlotinib (CP-358774) (0.01-10 μM; 5 minutes) potently inhibits human OATP2B1 in MDCKII-OATP2B1 cells, with an IC₅₀ of 0.079 μM^[3].
The uptake of erlotinib (approximately 0.016 μM; 7.5 minutes at pH 7.4 or 5.5) in MDCKII-OATP2B1 cells is significantly higher than that in wild-type MDCKII cells, with a 2.5-fold increase at pH 7.4 and a 3.3-fold increase at pH 5.5, which confirms that erlotinib is a substrate of human OATP2B1^[3].
Erlotinib (25 μM; 15 minutes) is metabolized by recombinant rat CYP3A1 and CYP3A2 into its metabolite OSI-420, with similar formation rates of approximately 0.20 ng/pmol CYP3 per minute^[3].
Erlotinib (5-10 μM) potently inhibits Ephrin A1-induced activation of EGFR and ERK in human gastric cancer cell line NCI-N87^[1].
Erlotinib (5-10 μM; 2 weeks) completely inhibits Ephrin A1-induced anchorage-independent colony formation in the human gastric cancer cell line NCI-N87^[1].
Erlotinib (5-10 μM) significantly inhibits ephrin A1-induced transendothelial migration of human gastric cancer cell line NCI-N87 across human umbilical vein endothelial cell (HUVEC) monolayers^[1].
Erlotinib (5-10 μM) inhibits ephrin A1-induced epithelial-mesenchymal transition (EMT) and EGFR activation in human gastric cancer AGS cells^[1].
Erlotinib (5-10 μM) inhibits Ephrin A1-induced invasion of human gastric cancer AGS cells, with 10 μM achieving nearly complete inhibition^[1].
Erlotinib (0.1-3 μM; 5 days) acts synergistically with the KRAS^G12D inhibitor MRTX1133 (HY-134813; 1-300 nM) to reduce the viability of Lkb1-knockout 634T mouse lung cancer spheroids, but exerts no such effect on Lkb1-intact 634T spheroids; significant synergistic effects are observed at erlotinib concentrations ranging from 100 nM to 3000 nM, with further enhanced efficacy at 1 μM^[2].
Erlotinib (2 μM; 1 h pre-incubation followed by 48 h rhMMP-10 exposure) potently inhibits MMP-10-mediated activation of the EGFR/ERK/GSK-3β/β-catenin signaling pathway and induction of pro-fibrotic markers in HK-2 cells^[4].
The IC₅₀ of Erlotinib (0-50 μM; 72 h) in erlotinib-resistant A549 cells is approximately 10-fold that of parental A549 cells^[5].
Erlotinib (15-30 μM; 6 months) induces the formation of an EGFR-independent drug-resistant phenotype in A549 and SK-LU-1 lung cancer cells, whereas Calu-1 cells do not acquire drug resistance under the same conditions^[5].
In erlotinib-resistant A549 cells, knockdown or knockout of GRHL2, knockdown of HER3, or knockout of E-cadherin all reduce the IC₅₀ of erlotinib, indicating that the GRHL2-HER3 axis and E-cadherin-mediated cell adhesion contribute to EGFR bypass resistance via relatively independent pathways^[5].
Erlotinib (5 μM; 24 h) does not induce apoptosis or autophagic cell death in parental or erlotinib-resistant A549 non-small cell lung cancer cells^[5]. In Vivo:Erlotinib (CP-358774) (50 mg/kg; intravenous injection; three times per week; for 6 consecutive weeks) reduces lung metastasis of Ephrin A1-overexpressing gastric cancer cells in SCID mice, decreasing the average lung weight by approximately 60% and the average number of metastatic nodules by approximately 80%^[1].
The systemic exposure of erlotinib (15.5 mg/kg; p.o.; single administration) and its metabolite OSI-420 in male Wistar rats is not significantly altered by human OATP2B1, but human OATP2B1 increases the mean residence time of OSI-420 by approximately 30%^[3].
Erlotinib (40-80 mg/kg/day; oral administration; daily dosing; consecutive 5 days) alleviates MMP-10-mediated renal injury and fibrotic lesions in UUO mice in a dose-dependent manner by inhibiting the EGFR/ERK/GSK-3β/β-catenin signaling cascade^[4].
Erlotinib (25 mg/kg; i.p.; administered daily from Monday to Friday for 4 consecutive weeks) significantly inhibits the growth of parental A549 non-small cell lung cancer xenografts in nude mice^[5].