h1975

Osimertinib (AZD-9291) is an EGFR third-generation inhibitor that inhibits the T790M resistance mutation produced by second-generation EGFR inhibitors with irreversible and oral activity. Osimertinib has antitumor activity for the treatment of EGFR-mutated non-small-cell lung cancer.

Osimertinib mesylate (AZD-9291 mesylate) is an EGFR third-generation inhibitor that inhibits the T790M resistance mutation produced by second-generation EGFR inhibitors with irreversible and oral activity. Osimertinib mesylate has antitumor activity for the treatment of EGFR-mutated non-small-cell lung cancer.

Zipalertinib (TAS6417, CLN-081) is a novel, highly potent, orally active covalent EGFR tyrosine kinase inhibitor that uniquely binds to the ATP binding site of the EGFR hinge region with an IC50 value of 1.1-8.0 nM.

E3330 is a potent and selective APE1(Ref-1) inhibitor, which suppressed NF-kappa B DNA-binding activity.

Panitumumab is a fully human IgG2 monoclonal antibody targeting the epidermal growth factor receptor EGFR).

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.

PF-06459988 is a novel, effective, orally active, irreversible, and selective epidermal growth factor receptor (EGFR) mutant inhibitor. PF-06459988 has high efficiency and high affinity for EGFRs double mutants containing T790M, and has minimal activity against WT EGFR. PF-06459988 makes a candidate drug for the treatment of cancer.

OTUB1/USP8-IN-1 is a potent OTUB1/USP8 inhibitor with potential anticancer activity, demonstrating IC50 values of 0.17 nM for OTUB1 and 0.28 nM for USP8. OTUB1/USP8-IN-1 can be used in the study of non-small-cell lung cancer.

Erlotinib (NSC-718781) is an EGFR inhibitor (IC50: 2 nM). It is used for the treatment of non-small cell lung cancer.

Afatinib Dimaleate (BIBW 2992MA2) is an orally bioavailable anilino-quinazoline derivative and inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with antineoplastic activity.

Afatinib (BIBW 2992) is an irreversible inhibitor of the EGFR family (EGFR-wt, EGFR-L858R, EGFR-L858R/T790M, and HER2) with IC50s of 0.5 nM, 0.4 nM, 10 nM, and 14 nM, respectively.

EGFR-IN-2 is a non-covalent, orally available and mutation-selective EGFR inhibitor for the treatment of non-small cell lung cancer (NSCLC), with high selectivity for resistant single and double mutant T790M with IC50 = 27 nm to 33 nM, and low inhibitory activity for wild-type H292 (IC50 = 218 nM).

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.

WK88-1, an inhibitor of Hsp90, effectively induces the degradation of various oncogenic signaling molecules, including EGFR, ErbB2, and ErbB3, in the gefitinib-resistant H1975 cell line. This leads to subsequent growth arrest and apoptosis.

NS-062 is an orally effective, irreversible covalent inhibitor targeting EGFR, demonstrating antiproliferative activity in the resistant double mutant H1975 cells with an IC50 of 0.19 μM. It also exhibits antitumor activity in a murine H1975 xenograft model.

EGFR-IN-139 (compound PD 18) is an EGFR inhibitor with IC50 values of 12.88 nM (wild type), 10.84 nM (L858R T790M), and 42.68 nM (L858R T790M C797S). It demonstrates significant anticancer activity against the A549 and H1975 cancer cell lines, which express high levels of EGFR. EGFR-IN-139 exhibits strong selectivity for cancer cells and can be utilized in research on non-small cell lung cancer (NSCLC).

JAK-IN-40 (Compound 46) is an inhibitor of JAK, effectively targeting JAK1, JAK2, and JAK3 with IC50 values of 0.022, 0.759, and 1.601 μM, respectively. It reduces the phosphorylation of STAT3 and inhibits the proliferation of cancer cells Ba F3 and JAK1-TEL Ba F3 with GI50 values of 0.614 μM and 0.193 μM. JAK-IN-40 arrests cell cycle progression at the G2 M phase in H1975 and H2087 cells, leading to apoptosis. Additionally, JAK-IN-40 exhibits a synergistic anti-tumor effect when used in combination with Osimertinib.

ALK/PI3K/AKT-IN-1 (Compound 45) effectively inhibits the proliferation of cancer cell lines A549, H1975, and PC9, with IC50 values of 0.44, 0.83, and 1.51 μM, respectively. This compound enhances the expression of p21 and p27, and decreases the activity of CDK2 and p-Rb, causing cell cycle arrest at the G1 phase. It suppresses the ALK/PI3K/AKT signaling pathway, promotes mitochondrial membrane potential depolarization, and induces apoptosis in A549 cells. Furthermore, ALK/PI3K/AKT-IN-1 inhibits the formation and growth of A549 cell spheres.

EGFR-IN-150 is an EGFR inhibitor that effectively inhibits the phosphorylation of mutant epidermal growth factor receptor (EGFR) and its downstream AKT signaling pathway, exerting antitumor effects and inducing HMOX1 expression to trigger ferroptosis. This compound exhibits an IC50 of 0.386 μM against the non-small cell lung cancer (NSCLC) cell line H1975 and significantly suppresses the colony formation and migration abilities of H1975 and A549 cells, while also inducing apoptosis. Additionally, EGFR-IN-150 prominently reduces tumor growth in H1975 tumor-bearing mouse CDX models. It holds promise for research related to non-small cell lung cancer.

EGFR-IN-151 (Compound 10) inhibits EGFR and its downstream signaling pathways ERK/STAT3. It effectively suppresses the proliferation of various lung cancer cells, with IC50 values of 11.7, 5.19, 7.32, and 1.53 μM for NCI-H1781, HCC827, NCI-H3255, and NCI-H1975, respectively. Additionally, EGFR-IN-151 hinders colony formation and cell migration in H1975, induces G1 phase cell cycle arrest, and triggers apoptosis in H1975 cells.

Lazertinib (mesylate) (YH25448 (mesylate); GNS-1480 (mesylate)) is an orally active EGFR inhibitor capable of crossing the blood-brain barrier. It suppresses the p-EGFR, p-AKT, and p-ERK signaling pathways, leading to apoptosis. Lazertinib (mesylate) demonstrates antitumor activity in the H1975-luc BM xenograft model in mice and is applicable for researching non-small cell lung cancer.

PF-6274484, a high affinity, irreversible covalent inhibitor of EGFR kinase with Ki of 0.14 nM, inhibits the autophosphorylation of wild-type EGFR in A549 cells and EGFRL858R T790M in H1975 cells with IC50 of 5.8 nM and 6.6 nM, respectively.

Limertinib (ASK120067) is an orally active and highly efficient epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR T790M. Limertinib can be used for studying non-small cell lung cancer.

Rezivertinib (BPI-7711) is an orally available, selective and potent inhibitor of tyrosine kinase (EGFR) with antitumor activity for central nervous system disorders.