Fig. 1: Development of an EGFR-TKI-based fluorogenic probe to quantify active-EGFR for stratification of NSCLC patients. | Nature Communications

Fig. 1: Development of an EGFR-TKI-based fluorogenic probe to quantify active-EGFR for stratification of NSCLC patients.

From: A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations

Fig. 1

a Schematic of EGFR-TKI explaining the benefits to NSCLC patients through a stratification strategy using the combination of a fluorogenic probe and DNA sequencing analysis to guide treatment and clinical trial choices for patients with EGFR-mutant NSCLC. b Structure-based design of a fluorogenic probe by incorporating the environment-sensitive fluorophore (SBD) into the pharmacophore of EGFR-TKI (e.g., gefitinib) and illustration of the probe turn-on property: the probe shows low fluorescence in the absence of EGFR, whereas it can exhibit stronger fluorescence by binding to the kinase domain of EGFR. c Predicted binding modes of HX103 with EGFR wild-type (PDB: 4WKQ), EGFR L858R mutant (PBD: 4LQM), and EGFR L858R/T790M (PDB: 5EDP). d Synthesis of HX103 (9), reagents and conditions: (a) 3-chloro-4-fluoroaniline (2), i-PrOH, DCM, reflux, 4 h, 91% (3); (b) TFA, 70 °C, ammonium hydroxide, 96% (4); (c) tert-butyl (3-bromopropyl)carbamate (5), K2CO3, DMF, 80 °C, 4 h, 78% (6); (d) TFA, r.t., 1 h, 70% (7); (e) 7-fluoro-N,N-dimethylbenzo[c][1,2,5] oxadiazole-4-sulfonamide (8), acetonitrile, Et3N, r.t., 1 h, 23% (9).

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