5gmp › Citations

A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFRL858R/T790M mutant with improved pharmacokinetic properties.

Yu L, Huang M, Xu T, Tong L, Yan XE, Zhang Z, Xu Y, Yun C, Xie H, Ding K, Lu X
Eur J Med Chem 126 1107-1117 (2017)
Cited: 13 times
EuropePMC logo PMID: 28033579

Abstract

Structural optimization of pyrido[2,3-d]pyrimidin-7-ones was conducted to yield a series of new selective EGFRT790M inhibitors with improved pharmacokinetic properties. One of the most promising compound 9s potently suppressed EGFRL858R/T790M kinase and inhibited the proliferation of H1975 cells with IC50 values of 2.0 nM and 40 nM, respectively. The compound dose-dependently induced reduction of the phosphorylation of EGFR and downstream activation of ERK in NCIH1975 cells. It also exhibited moderate plasma exposure after oral administration and an oral bioavailability value of 16%. Compound 9s may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer (NSCLC) patients.

Articles - 5gmp mentioned but not cited (5)

  1. Structural basis of lariat RNA recognition by the intron debranching enzyme Dbr1. Montemayor EJ, Katolik A, Clark NE, Taylor AB, Schuermann JP, Combs DJ, Johnsson R, Holloway SP, Stevens SW, Damha MJ, Hart PJ. Nucleic Acids Res 42 10845-10855 (2014)
  2. Surveying biomolecular frustration at atomic resolution. Chen M, Chen X, Schafer NP, Clementi C, Komives EA, Ferreiro DU, Wolynes PG. Nat Commun 11 5944 (2020)
  3. The 23S Ribosomal RNA From Pyrococcus furiosus Is Circularly Permuted. Birkedal U, Beckert B, Wilson DN, Nielsen H. Front Microbiol 11 582022 (2020)
  4. Design, synthesis, and biological evaluation of 4-(2-fluorophenoxy)-7-methoxyquinazoline derivatives as dual EGFR/c-Met inhibitors for the treatment of NSCLC. Tang S, Sun C, He X, Gan W, Wang L, Qiao D, Guan X, Xu S, Zheng P, Zhu W. Eur J Med Chem 263 115939 (2024)
  5. YL143, a novel mutant selective irreversible EGFR inhibitor, overcomes EGFRL858R, T790M -mutant resistance in vitro and in vivo. Zhang Z, Zou J, Yu L, Luo J, Li Y, Tu Z, Ren X, Wei H, Song L, Lu X, Ding K. Cancer Med 7 1430-1439 (2018)


Reviews citing this publication (3)

  1. Targeting EGFRL858R/T790M and EGFRL858R/T790M/C797S resistance mutations in NSCLC: Current developments in medicinal chemistry. Lu X, Yu L, Zhang Z, Ren X, Smaill JB, Ding K. Med Res Rev 38 1550-1581 (2018)
  2. Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications. Jubete G, Puig de la Bellacasa R, Estrada-Tejedor R, Teixidó J, Borrell JI. Molecules 24 E4161 (2019)
  3. A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure-Activity Relationship. Yadav TT, Moin Shaikh G, Kumar MS, Chintamaneni M, Yc M. Front Chem 10 861288 (2022)

Articles citing this publication (5)

  1. Discovery of JND3229 as a New EGFRC797S Mutant Inhibitor with In Vivo Monodrug Efficacy. Lu X, Zhang T, Zhu SJ, Xun Q, Tong L, Hu X, Li Y, Chan S, Su Y, Sun Y, Chen Y, Ding J, Yun CH, Xie H, Ding K. ACS Med Chem Lett 9 1123-1127 (2018)
  2. Design, synthesis, and anti-cancer evaluation of new pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as potential EGFRWT and EGFRT790M inhibitors and apoptosis inducers. Elzahabi HSA, Nossier ES, Alasfoury RA, El-Manawaty M, Sayed SM, Elkaeed EB, Metwaly AM, Hagras M, Eissa IH. J Enzyme Inhib Med Chem 37 1053-1076 (2022)
  3. Discovery of Potent EGFR Inhibitors With 6-Arylureido-4-anilinoquinazoline Derivatives. Li M, Xue N, Liu X, Wang Q, Yan H, Liu Y, Wang L, Shi X, Cao D, Zhang K, Zhang Y. Front Pharmacol 12 647591 (2021)
  4. How Different Substitution Positions of F, Cl Atoms in Benzene Ring of 5-Methylpyrimidine Pyridine Derivatives Affect the Inhibition Ability of EGFRL858R/T790M/C797S Inhibitors: A Molecular Dynamics Simulation Study. E J, Liu Y, Guan S, Luo Z, Han F, Han W, Wang S, Zhang H. Molecules 25 E895 (2020)
  5. Proteome-wide Identification of Off-Targets of a Potent EGFRL858R/T790M Mutant Inhibitor. Lyu P, Jiang K, Zhou Y, Hu J, Chang Y, Zhang Z, Huang M, Zhang ZM, Ding K, Hao P, Lin L, Li Z. ACS Med Chem Lett 13 292-297 (2022)


Quick links