egfrdel19 t790m

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-127 is an ATP-competitive inhibitor targeting EGFR, with IC50 values of 136.3 nM for EGFRdel19 and 161.2 nM for EGFRdel19 T790M C797S. This compound holds potential for the study of non-small cell lung cancer (NSCLC).

EGFR-IN-140 (Compound 31) is an inhibitor of EGFR, effectively targeting both wild-type EGFR and the EGFRL858R T790M C797S mutant, with Ki values of 0.95 nM and 2.1 nM, respectively. Additionally, it inhibits EGFRdel19 T790M C797S in Ba F3 cells with an IC50 of 56.9 nM and demonstrates antitumor activity in mouse models.

PROTAC EGFR degrader 4 is a potent molecule designed to target and degrade mutant EGFR, effectively inducing degradation of EGFR del19 and EGFR L858R T790M with DC50 values of 0.51 nM and 126 nM, respectively. It significantly inhibits the growth of HCC827 and H1975 cell lines, demonstrating IC50 values of 0.83 nM and 203.1 nM, respectively. The induced degradation of EGFR by this compound is associated with autophagy [1].

EGFR-IN-82 (Compound 8a) is a potent, orally active inhibitor of EGFR, exhibiting IC50 values of 0.09 nM for EGFR L858R T790M C797S and 0.06 nM for EGFR Del19 T790M C797S. It lacks significant inhibitory effects on EGFR WT. Demonstrating anti-proliferative properties, EGFR-IN-82 also inhibits tumor growth in nude mice, rendering it applicable in non-small cell lung cancer research [1].

Os30 is a potent fourth-generation EGFR inhibitor, specifically targeting the EGFRC797S-TK mutation with IC50 values of 18 nM for EGFRDel19 T790M C797S TK and 113 nM for EGFRL858R T790M C797S TK. It effectively suppresses EGFR phosphorylation, induces G1 phase arrest, and triggers apoptosis in KC-0116 (BaF3-EGFRDel19 T790M C797S) cells. Moreover, Os30 demonstrates strong antitumor activity in non-small cell lung cancer (NSCLC) harboring the EGFmRC797S mutation [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].

EGFR-IN-104 (Compound A23) acts as a potent EGFR inhibitor, demonstrating IC50 values of 0.33 μM for EGFR L858R T790M and 0.133 μM for EGFR Del19 T790M C797S. It exhibits anticancer properties, effective both in vitro and in vivo [1].

EGFR-IN-97 (compound 6q), an EGFR inhibitor, demonstrates effectiveness in inhibiting Ba F3-EGFR L858R T790M C797S and Ba F3-EGFR Del19 T790M C797S cells, exhibiting IC 50 values of 0.42 μM and 0.41 μM, respectively. Additionally, at a concentration of 0.8 μM, EGFR-IN-97 is capable of inducing apoptosis in NCI-H1975-EGFR L858R T790M C797S cells [1].