osimertinib

Osimertinib (AZD-9291) 是一种 EGFR 三代抑制剂，抑制二代 EGFR 抑制剂产生的 T790M 耐药突变，具有不可逆性和口服活性。Osimertinib 具有抗肿瘤活性，用于治疗 EGFR 突变的非小细胞肺癌。

Osimertinib mesylate (AZD-9291 mesylate) 是一种 EGFR 三代抑制剂，抑制二代 EGFR 抑制剂产生的 T790M 耐药突变，具有不可逆性和口服活性。Osimertinib mesylate 具有抗肿瘤活性，用于治疗 EGFR 突变的非小细胞肺癌。

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

Mutated EGFR-IN-1 (Osimertinib analog) 是用于突变 EGFR 抑制剂设计的有用中间体，例如 L858R EGFR、Exon19 缺失激活突变体和 T790M 抗性突变体。

Osimertinib-d6 是 Osimertinib 的氘代化合物。Osimertinib 的 CAS 号为 1421373-65-0。Osimtinib 是一种小分子酪氨酸激酶受体抑制剂和抗肿瘤剂，用于治疗选定形式的晚期非小细胞肺癌，其有效抑制 L858R 和 L858R T790M EGFR，IC50 为 12 和 1 nM。

Dosimertinib-d3是一种有效的口服活性EGFR 抑制剂。Dosimertinib-d3降低 p-EGFR 和 p-ERK 蛋白水平的表达。Dosimertinib-d3显示出抗增殖和抗肿瘤活性。Dosimertinib-d3具有非小细胞肺癌 (NSCLC) 研究的潜力。

JAK-IN-40 (Compound 46) 是一种JAK抑制剂，可有效抑制JAK1、JAK2和JAK3，IC50分别为0.022、0.759和1.601 μM。JAK-IN-40 抑制STAT3的磷酸化，并抑制癌细胞Ba F3和JAK1-TEL Ba F3的增殖，其GI50值分别为0.614 μM和0.193 μM。该化合物使H1975和H2087细胞在G2 M期停滞，诱导细胞凋亡(apoptosis)。与Osimertinib联合使用时，JAK-IN-40表现出协同抗肿瘤作用。

CDK9-IN-36 (Compound T7) 是一种高效、选择性且代谢稳定的CDK9抑制剂，IC50值为1.2 nM。通过下调Mcl-1，CDK9-IN-36 有效抑制对Osimertinib耐药的NSCLC细胞的增殖，减少集落形成，诱导凋亡 (apoptosis)。在异种移植模型中，CDK9-IN-36 同样展现了抗肿瘤活性。

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.

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 是一种甲磺酸奥希替尼的工艺杂质, 可用于非小细胞肺癌的研究。

Becotatug (JMT-101)为一种针对EGFR的IgG1类单克隆抗体，具备与Afatinib及Osimertinib偶联生成ADC(抗体偶联药物)的潜力。

HJM-561为一种有效的选择性口服生物可利用EGFRPROTAC，能够克服osimertinib耐药的EGFR三重突变，并表现出抗肿瘤活性。

ONO-7475 是一种选择性的、有效的、具有口服活性的Axl Mer 抑制剂。它使 AXL 过表达的EGFR 突变型 NSCLC 细胞对 EGFR-TKIs 敏感，抑制耐药细胞的产生和耐药性的维持。它与 Osimertinib 联合使用，具有用于 EGFR 突变非小细胞肺癌的潜力。

LS-106 是一种高效的口服表皮生长因子受体 (EGFR) 抑制剂，具有显著的抗肿瘤活性，无论是在体外还是体内。该化合物尤其针对 EGFR19del T790M C797S 和 EGFRL858R T790M C797S 激酶活性表现出强大的抑制能力，IC50 值分别仅为 2.4 nmol L 和 3.1 nmol L，抑制效果优于 Osimertinib。此外，LS-106 能有效诱导肿瘤细胞凋亡 (Apoptosis) 并抑制携带 EGFR19del T790M C797S 突变的肿瘤细胞增殖，同时在 C797S 突变异种移植模型中显著缩小肿瘤体积。