Discovery of novel, potent, selective and orally bioavailable HPK1 inhibitor for enhancing the efficacy of anti-PD-L1 antibody.

Hematopoietic progenitor kinase 1 (HPK1), a serine/threonine kinase in the MAP4K family, is expressed predominantly in immune cells, and has been identified as a negative regulator of immune signaling. Accumulating evidences demonstrated that loss of HPK1 kinase function effectively enhances anti-tumor responses. In this study, we disclose the medicinal chemistry campaigns to discovery potent, selective, and orally active HPK1 inhibitors, starting from our previous work based on rigidification strategy.

Discovery of potent and selective HPK1 inhibitors based on the 2,4-disubstituted pyrimidine scaffold with immune modulatory properties for ameliorating T cell exhaustion.

Hematopoietic progenitor kinase 1 (HPK1), a member of the mitogen-activated protein kinase (MAP4K) family, is a serine/threonine (SER/THR) kinase and has been demonstrated as a negative regulator of T cell receptor signaling. Targeting HPK1 has been considered as an attractive therapeutic strategy for immune-oncology. Here, we describe the discovery and structure-activity relationship (SAR) of potent HPK1 inhibitors based on the 2,4-disubstituted pyrimidine scaffold.

Discovery of novel pyrrolo [2,3-d] pyrimidine derivatives as potent FAK inhibitors based on cyclization strategy.

Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, plays a pivotal role in tumor invasion and metastasis. Many FAK inhibitors had been reported, but the development of FAK inhibitors in clinical studies are still limited. To facilitate the discovery of FAK modulators and further elucidate the role of FAK in cancer metastasis, it is necessary to discover a novel, potent and selective FAK inhibitor.

Relationship between marital status and survival in patients with lung adenocarcinoma: A SEER-based study.

Numerous studies have focused on whether the marital status has an impact on the prognosis in patients with non-small cell lung cancer, but none have focused on lung adenocarcinoma.We selected 61,928 eligible cases with lung adenocarcinoma from the Surveillance, Epidemiology, and End Results database from 2004 to 2016 and analyzed the impact of marital status on cancer-specific survival (CSS) using Kaplan-Meier and Cox regression analyses.We confirmed that sex, age, race, cancer TNM stage and grade, therapeutic schedule, household income, and marital status were independent prognostic factors for lung adenocarcinoma CSS.

Clinical efficacy and safety of maintenance therapy for advanced non-small cell lung cancer: a retrospective real-world study.

Background: The clinical efficacy and safety of maintenance therapy (MT) for patients with advanced non-small cell lung cancer (NSCLC) have not been determined in the real word. This retrospective study of real-world data analyzed these issues in patients with advanced NSCLC and stable or responsive tumors after 4-6 cycles of first-line chemotherapy.

Methods: We classified 158 patients into MT (34 IIIB and 37 IV stage) and non-MT (47 IIIB and 40 IV stage) groups and then compared the clinical outcomes of progression-free survival (PFS) and overall survival (OS).