Synthesis and biological evaluation of anilide derivatives as epidermal growth factor receptor <scp>L858R</scp>/<scp>T790M</scp> and <scp>L858R</scp>/<scp>T790M</scp>/<scp>C797S</scp> inhibitors

Kim, Soo Lim; Yang, Yo‐Sep; Kim, Nam‐Jung

doi:10.1002/bkcs.12578

Cited by 5 publications

(2 citation statements)

References 7 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We collected 30 papers published in recent years, which focus on small-molecule inhibitors of EGFR L858R/T790M/C797S triple mutations and compiled a data set containing 221 valuable active structures and their corresponding kinase inhibitory activities (expressed as IC 50 ). − For screening efficiency, only structures with IC 50 < 5 μM and with accurate numerical representation have been retained in the collation. The activity values were converted to the pIC 50 (−log 10 (IC 50 )) for the sake of the same magnitude on our data.…”

Section: Materials and Methodsmentioning

confidence: 99%

Machine Learning-Based Virtual Screening and Identification of the Fourth-Generation EGFR Inhibitors

Chang,

Zhang,

Tian

et al. 2024

ACS Omega

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) plays a pivotal regulatory role in treating patients with advanced nonsmall cell lung cancer (NSCLC). Following the emergence of the EGFR tertiary CIS C797S mutation, all types of inhibitors lose their inhibitory activity, necessitating the urgent development of new inhibitors. Computer systems employ machine learning methods to process substantial volumes of data and construct models that enable more accurate predictions of the outcomes of new inputs. The purpose of this article is to uncover innovative fourth-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with the aid of machine learning techniques. The paper's data set was high-dimensional and sparse, encompassing both structured and unstructured descriptors. To address this considerable challenge, we introduced a fusion framework to select critical molecule descriptors by integrating the full quadratic effect model and the Lasso model. Based on structural descriptors obtained from the full quadratic effect model, we conceived and synthesized a variety of small-molecule inhibitors. These inhibitors demonstrated potent inhibitory effects on the two mutated kinases L858R/T790M/C797S and Del19/T790M/C797S. Moreover, we applied our model to virtual screening, successfully identifying four hit compounds. We have evaluated these hit ADME characteristics and look forward to conducting activity evaluations on them in the future to discover a new generation of EGFR-TKI.

show abstract

Section: Materials and Methodsmentioning

confidence: 99%

Machine Learning-Based Virtual Screening and Identification of the Fourth-Generation EGFR Inhibitors

Chang,

Zhang,

Tian

et al. 2024

ACS Omega

View full text Add to dashboard Cite

show abstract

“…Heterocyclic compounds are frequently identified and play an important role in human life due to their special structures. For example, heterocyclic structures are related to many biological processes and form the basic skeleton of many drug molecules and natural products [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. N -heterocycles, which contain nitrogen atoms, have attracted much attention from scientists because of their unique properties and diverse utilization.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Synthetic Routes to Azacycles

Nguyen

Kim

2023

Molecules

View full text Add to dashboard Cite

A heterocycle is an important structural scaffold of many organic compounds found in pharmaceuticals, materials, agrochemicals, and biological processes. Azacycles are one of the most common motifs of a heterocycle and have a variety of applications, including in pharmaceuticals. Therefore, azacycles have received significant attention from scientists and a variety of methods of synthesizing azacycles have been developed because their efficient synthesis plays a vital role in the production of many useful compounds. In this review, we summarize recent approaches to preparing azacycles via different methods as well as describe plausible reaction mechanisms.

show abstract

Improvement of the metabolic stability of pan‐RAF/VEGFR2 dual inhibitors

Maiti,

Kwon,

Hong

et al. 2023

Bulletin Korean Chem Soc

View full text Add to dashboard Cite

Development of dual inhibitors of pan‐RAF/VEGFR2 is important for the treatment of K‐Ras mutated colorectal cancer, which is one of the most common and lethal malignancies. Building upon our studies in dual inhibitors of pan‐RAF/VEGFR2, we designed and synthesized new dual inhibitor candidates by installing a urea or guanidine moiety to the previously reported dual inhibitors in order to enhance both metabolic stability and solubility. Various 1‐(5‐((3‐(9H‐purin‐6‐yl)pyridin‐2‐yl)amino)‐2‐fluorophenyl)‐3‐phenylurea and 1‐(5‐((3‐(9H‐purin‐6‐yl)pyridin‐2‐yl)amino)‐2‐fluorophenyl)‐3‐phenylguanidine derivatives were synthesized, and their antiproliferative activities against LS513 cell (K‐RasG12D) and VEGFR2 were evaluated. Among the tested compounds, 1‐(5‐((3‐(9H‐purin‐6‐yl)pyridin‐2‐yl)amino)‐2‐fluorophenyl)‐3‐(3‐fluorophenyl)urea (7b) and 1‐(5‐((3‐(9H‐purin‐6‐yl)pyridin‐2‐yl)amino)‐2‐fluorophenyl)‐3‐(4‐chloro‐3‐trifluoromethyl)phenyl)urea (7e) are the most potent dual inhibitors against LS513 (GI50 = 0.1 and 0.06 μM, respectively) and VEGFR2 (IC50 = 0.03 and 0.06 μM, respectively). The preclinical study with these compounds are currently underway.

show abstract

Synthesis and biological evaluation of anilide derivatives as epidermal growth factor receptor L858R/T790M and L858R/T790M/C797S inhibitors

Cited by 5 publications

References 7 publications

Machine Learning-Based Virtual Screening and Identification of the Fourth-Generation EGFR Inhibitors

Machine Learning-Based Virtual Screening and Identification of the Fourth-Generation EGFR Inhibitors

Recent Advances in Synthetic Routes to Azacycles

Improvement of the metabolic stability of pan‐RAF/VEGFR2 dual inhibitors

Contact Info

Product

Resources

About