osimertinib

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.

Osimertinib-d6 is a deuterated compound of Osimertinib. Osimertinib has a CAS number of 1421373-65-0. Osimertinib is a small molecule tyrosine kinase receptor inhibitor and antineoplastic agent that is used in the therapy of selected forms of advanced non-small cell lung cancer (NSCLC).

Osimertinib dimesylate is an irreversible and mutant selective EGFR inhibitor (IC50s: 12 and 1 nM against EGFR L858R and EGFR L858R T790M).

Dosimertinib-d3 is a potent, orally active inhibitor of EGFR, known to reduce the expression of p-EGFR and p-ERK proteins, thereby exhibiting antiproliferative and anti-tumor effects. It holds promise for research into non-small-cell lung cancer (NSCLC).

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.

DBPR112 is a potent EGFR inhibitor (IC50=487 nM) as a Clinical Candidate for the Treatment of Non-Small Cell Lung Cancer. DBPR112), DBPR112 not only displayed a potent inhibitory activity against EGFRL858R T790M double mutations but also exhibited tenfold potency better than the third-generation inhibitor, osimertinib,against EGFR and HER2 exon 20 insertion mutations. Overall, pharmacokinetic improvement through lead-to-candidate optimization yielded fourfold oral AUC better that afatinib along with F = 41.5%, an encouraging safety profile, and significant antitumor efficacy in in vivo xenograft models.

ONO-7475 is an inhibitor with high specificity for anexelekto and MER tyrosine kinase

HJM-561 is a potent and selective EGFR PROTAC with oral bioavailability, capable of overcoming osimertinib-resistant EGFR triple mutations and demonstrating anti-tumor activity [1].

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.

CDK9-IN-36 (Compound T7) is a potent, selective, and metabolically stable CDK9 inhibitor with an IC50 value of 1.2 nM. It effectively suppresses the proliferation of Osimertinib-resistant NSCLC cells by downregulating Mcl-1, reducing colony formation, and inducing apoptosis. Additionally, CDK9-IN-36 exhibits antitumor activity in xenograft models.

LS-106 is an orally active, effective epidermal growth factor receptor (EGFR) inhibitor displaying antitumor activity both in vitro and in vivo. It inhibits the kinase activities of EGFR19del T790M C797S and EGFRL858R T790M C797S, with IC50 values of 2.4 nmol L and 3.1 nmol L, respectively, demonstrating stronger inhibition than Osimertinib. LS-106 induces cell apoptosis (Apoptosis), suppresses the proliferation of tumor cells carrying EGFR19del T790M C797S, and results in significant tumor reduction in a C797S mutant xenograft model.

Olmutinib is a novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor, used in the treatment of T790M mutation positive non-small cell lung cancer. Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. EGFRs are frequently over-expressed in lung cancer and contribute to activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways which both promote cell survival and proliferation. By inhibiting EGFR activation, Olmutinib attenuates the activation of these tumor-promoting pathways. In the first phase I II clinical study of Osimertinib, 800 mg day was chosen as the dose for subsequent studies, and the dose-limiting toxicity and maximum tolerated dose was not reached. Olmutinib received breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.

Rezivertinib analogue 1, a process impurity of osimertinib mesylate, serves as a research tool in the study of non-small cell lung cancer (NSCLC) [1].

Becotatug (JMT-101) is an IgG1 antibody targeting EGFR, which can be conjugated to Afatinib and Osimertinib, serving as a synthetic antibody-drug conjugate (ADC) [1].