egfr mutant-in-1

EGFR mutant- in-1, A 5-methylpyrimidopyridone derivative are effective selective EGFRL858R T790M C797S mutant inhibitors with IC50 of 27.5 nM, which significantly weakened EGFRWT effect.

BI-4020 is a fourth-generation, orally active, and non-covalent inhibitor of EGFR tyrosine kinase. It exhibits activity against the triple mutant EGFR del19 T790M C797S variant (IC50=0.2 nM in BaF3 cell lines), the double mutant EGFR del19 T790M and primary mutant EGFR del19 (IC50=1 nM), and EGFR wt (IC50=190 nM). BI-4020 also shows high kinome selectivity and good DMPK properties.

EGFR-IN-1 hydrochloride is an irreversible and specific inhibitor of L858R T790M mutant EGFR, with 100-fold selectivity over wild-type EGFR. It exhibits potent antitumor and antiproliferative activity in H1975 cells and mutant HCC827 cells with IC50s of 4 and 28 nM, respectively.

SU11652 is an effective and competitive receptor tyrosine kinase (RTK) inhibitor, including VEGFR, FGFR, PDGFR, and Kit. SU11652 disrupts the function of all forms of mutant Kit and may be used in the study of cancers involving Kit mutations.

Mutated EGFR-IN-1 (Osimertinib analog) is a valuable intermediate in designing inhibitors for mutated EGFR, including L858R EGFR, Exon19 deletion activating mutant, and T790M resistance mutant.

EGFR-IN-1, an orally active and irreversible selective inhibitor targeting L858R T790M mutant EGFR, exhibits strong antiproliferative and antitumor activity, particularly against H1975 cells and first line mutant HCC827 cells. This compound potently inhibits Gefitinib-resistant EGFR L858R T790M mutations with a 100-fold selectivity over the wild-type EGFR.

HKB99 is a mutant inhibitor of phosphoglycerate mutase 1 (PGAM1), which inhibits the growth and metastasis of non-small cell lung cancer.HKB99 acts synergistically with EGFR inhibitors and assists in the killing of tumors by EGFR inhibitors.HKB99 promotes oxidative stress, which induces alterations in a variety of signaling pathways.HKB99 can be used in the study of metabolism-related diseases.HKB99 can be used in the study of metabolism-related diseases.HKB99 can be used in the study of metabolism-related diseases.

EMI1 can be used in the mutant EGFR-associated, drug-resistant non-small-cell lung cancer(NSCLC) research. EMI1 is an inhibitor of EGFR L858R T790M C797S and EGFR ex19del T790M C797S [1].

PROTAC EGFR Degrader 3, a highly potent molecule, exhibits remarkable cellular activity against H1975 and HCC827 cells, maintaining high selectivity. It additionally reveals the lysosome's crucial role in the degradation mechanism of mutant EGFR [1].

JBJ-09-063 TFA is a mutant-selective allosteric EGFR inhibitor with IC50 values of 0.147 nM for EGFR L858R, 0.063 nM for EGFR L858R T790M, 0.083 nM for EGFR L858R T790M C797S, and 0.396 nM for EGFR L747S mutations. It effectively reduces phosphorylation of EGFR, Akt, and ERK1 2, demonstrating efficacy in models both sensitive and resistant to EGFR tyrosine kinase inhibitors (TKI). JBJ-09-063 TFA holds potential for research in EGFR-mutant lung cancer [1].

MS9427 is a potent PROTAC EGFR degrader with dissociation constants (K d s) of 7.1 nM for wild-type (WT) EGFR and 4.3 nM for L858R mutant EGFR, demonstrating selective degradation of the mutant via ubiquitin proteasome system (UPS) and autophagy lysosome pathways. MS9427 effectively inhibits non-small cell lung cancer (NSCLC) cell proliferation, positioning it as a potential therapeutic agent in anticancer research [1].

MS9427 TFA is a potent PROTAC-based EGFR degrader, exhibiting dissociation constants (Kd) of 7.1 nM for wild-type EGFR and 4.3 nM for the L858R EGFR mutation. It preferentially degrades the mutant EGFR, sparing the wild-type form, utilizing both the ubiquitin proteasome system (UPS) and the autophagy lysosome pathways. Its efficacy extends to the significant inhibition of non-small cell lung cancer (NSCLC) cell proliferation, indicating its potential utility in anticancer research [1].

MS9449 is a potent PROTAC EGFR degrader, exhibiting dissociation constants (Kd) of 17 nM for EGFR WT and 10 nM for EGFR L858R. It effectively mediates the degradation of mutant EGFRs via both ubiquitin proteasome system (UPS) and autophagy lysosome pathways, robustly suppressing the proliferation of NSCLC cells, indicating its potential utility in anticancer research [1].

EGFR-IN-1 TFA is an orally active and irreversible L858R T790M mutant selective EGFR inhibitor. EGFR-IN-1 TFA potently inhibits Gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR . EGFR-IN-1 TFA displays strong antiproliferative activity against the H1975 cells and the first line mutant HCC827 cells. Antitumor activity [1] .

EGFR-IN-89 (compound 13k) is a fourth-generation inhibitor that selectively targets EGFR mutations, showing potent activity with an IC50 of 10.1 nM against Del19/T790M/C797S mutations, and demonstrating greater selectivity for mutant forms over wild type [1].

YS-363 is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor (EGFR), with half-maximal inhibitory concentrations (IC50) of 0.96 nM for the wild-type EGFR and 0.67 nM for the L858R mutant variant. It induces G0 G1 cell cycle arrest and apoptosis in targeted cells [1].

EGFR Kinase Inhibitor 4 (Compound 4) acts as a bivalent ATP-allosteric inhibitor targeting EGFR, with a potent inhibitory effect (IC 50: 1.8 nM) on mutant EGFR (LRTMCS). It is primarily utilized in the study of non-small cell lung cancer (NSCLC) [1].

EGFR ligand-2 (compound C4) is a covalent EGFR ligand and mutant inhibitor with IC50 values of 21 nM for EGFR L858R and 48 nM for EGFR L858R T790M. It can be utilized in the synthesis of PROTAC [1].

EGFR mutant-IN-2 (Compound D51) is an inhibitor of EGFR mutants, specifically targeting EGFR L858R T790M C797S and EGFR del19 T790M C797S mutants with IC50 values of 14 nM and 62 nM, respectively. This compound exhibits favorable pharmacokinetic (PK) parameters, safety properties, in vivo stability, and demonstrates antitumor activity [1].