Kinetic and thermodynamic insights into interaction of erlotinib with epidermal growth factor receptor: Surface plasmon resonance and molecular docking approaches

Mohammadzadeh-Asl, Saeideh; Aghanejad, Ayuob; Yekta, Reza; Guárdia, Miguel de la; Dolatabadi, Jafar Ezzati Nazhad; Keshtkar, Ahmad

doi:10.1016/j.ijbiomac.2020.07.048

Cited by 17 publications

(5 citation statements)

References 28 publications

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“…Assuming a simple two-state binding model, the plots were fit to a linear function, and the binding and dissociation rate constants, k on and k off , were obtained from the slope and the Y intercept, respectively. Since the Y intercept was negative for 57 , the k off was instead determined through a binding competition experiment with the orthosteric inhibitor erlotinib . For consistency, the same was carried out for 50 .…”

Section: Methodsmentioning

confidence: 99%

“…Since the Y intercept was negative for 57, the k off was instead determined through a binding competition experiment with the orthosteric inhibitor erlotinib. 33 For consistency, the same was carried out for 50. Briefly, 5 nM or 20 nM EGFR L858R was mixed with 5 nM 57 or 30 nM 50, respectively.…”

Section: -[4-(difluoromethyl)-6-[2-[4-[[4-(hydroxymethyl)-1-piperidyl...mentioning

confidence: 99%

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Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib

et al. 2022

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Addressing resistance to third-generation EGFR TKIs such as osimertinib via the EGFRC797S mutation remains a highly unmet need in EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we present the discovery of the allosteric EGFR inhibitor 57, a novel fourth-generation inhibitor to overcome EGFRC797S-mediated resistance in patients harboring the activating EGFRL858R mutation. 57 exhibits an improved potency compared to previous allosteric EGFR inhibitors. To our knowledge, 57 is the first allosteric EGFR inhibitor that demonstrates robust tumor regression in a mutant EGFRL858R/C797S tumor model. Additionally, 57 is active in an H1975 EGFRL858R/T790M NSCLC xenograft model and shows superior efficacy in combination with osimertinib compared to the single agents. Our data highlight the potential of 57 as a single agent against EGFRL858R/C797S and EGFRL858R/T790M/C797S and as combination therapy for EGFRL858R- and EGFRL858R/T790M-driven NSCLC.

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Section: Methodsmentioning

confidence: 99%

Section: -[4-(difluoromethyl)-6-[2-[4-[[4-(hydroxymethyl)-1-piperidyl...mentioning

confidence: 99%

Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib

et al. 2022

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“…The interaction of erlotinib with the EGFR on the cell surface was investigated by SPR. 210 The tumor suppressor gene p53 was detected in the amplified electrochemiluminescence (ECL) sensing system (Fig. 14B).…”

Section: Opticsmentioning

confidence: 99%

Recent progress of biosensors for the detection of lung cancer markers

Chen

Weng

et al. 2023

J. Mater. Chem. B

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“…The equilibrium dissociation constant (K D ) demonstrated the degree of dissociation of the compounds and the 50S ribosome in the equilibrium state [30]. A low K D value indicated that the binding affinity between the compound and the 50S ribosome was strong [31].…”

Section: Spr Measurementsmentioning

confidence: 99%

Discovery of Novel Pleuromutilin Derivatives as Potent Antibacterial Agents for the Treatment of MRSA Infection

et al. 2022

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A series of novel pleuromutilin derivatives containing nitrogen groups on the side chain of C14 were synthesized under mild conditions. Most of the synthesized derivatives displayed potent antibacterial activities. Compound 9 was found to be the most active antibacterial derivative against MRSA (MIC = 0.06 μg/mL). Furthermore, the result of time-kill curves showed that compound 9 had a certain inhibitory effect against MRSA in vitro. Moreover, according to a surface plasmon resonance (SPR) study, compound 9 (KD = 1.77 × 10−8 M) showed stronger affinity to the 50S ribosome than tiamulin (KD = 2.50 × 10−8 M). The antibacterial activity of compound 9 was further evaluated in an MRSA-infected murine thigh model. Compared to the negative control group, tiamulin reduced MRSA load (~0.7 log10 CFU/mL), and compound 9 performed a treatment effect (~1.3 log10 CFU/mL). In addition, compound 9 was evaluated in CYP450 inhibition assay and showed only moderate in vitro CYP3A4 inhibition (IC50 = 2.92 μg/mL).

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Kinetic and thermodynamic insights into interaction of erlotinib with epidermal growth factor receptor: Surface plasmon resonance and molecular docking approaches

Cited by 17 publications

References 28 publications

Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib

Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib

Recent progress of biosensors for the detection of lung cancer markers

Discovery of Novel Pleuromutilin Derivatives as Potent Antibacterial Agents for the Treatment of MRSA Infection

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