Design, synthesis and biological evaluation of a novel PSMA-PI3K small molecule drug conjugate.

Small molecule drug conjugates are an emerging targeted therapy for cancer treatment. Building upon the overexpressed prostate-specific membrane antigen (PSMA) in prostate cancer, we herein report the design and synthesis of a novel PSMA-PI3K small molecule drug conjugate 1. Conjugate 1 demonstrates potent inhibition against PI3K with an IC value of 0.

Design, Synthesis, and Bioevaluation of Novel Reversibly Photoswitchable PI3K Inhibitors Based on Phenylazopyridine Derivatives toward Light-Controlled Cancer Treatment.

Photopharmacology is an emerging approach for achieving light-controlled drug activity. Herein, we design and synthesize a novel series of photoswitchable PI3K inhibitors by replacing a sulfonamide moiety with an azo group in a 4-methylquinazoline-based scaffold. Through structure-activity relationship studies, compound is identified to be effectively switched between its - and -configuration under irradiation with proper wavelengths.

[Research Progress of Proteolysis Targeting Chimeria in NSCLC Therapy].

Proteolysis targeting chimeria (PROTAC) degrades target proteins by utilizing the ubiquitin-proteasome pathway, subverting the concept of traditional small molecule inhibitors. Among the common mutation targets of non-small cell lung cancer (NSCLC), PROTAC technology has successfully achieved the effective degradation of kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK ) and other proteins in preclinical studies. PROTAC drugs with their unique event-driven advantages, are expected to overcome acquired drug resistance caused by small molecule inhibitors and show good therapeutic potential for undruggable targets, thereby providing a new strategy for the treatment of NSCLC.

Cp*Co-catalyzed formal [4 + 2] cycloaddition of 2-phenyl-1-imidazoles to afford imidazo[1,2-]quinazoline derivatives.

A synthetic protocol based on Cp*Co-catalyzed C-H amidation/annulation of 2-aryl-1-imidazoles with 1,4,2-dioxazol-5-ones was developed to give imidazo[1,2-]quinazoline derivatives with broad substrate scope in moderate to good yields. The method has good prospects of application in the synthesis of imidazo[1,2-]quinazoline drugs.

Advances and Challenges of Fluorescent Nanomaterials for Synthesis and Biomedical Applications.

With the rapid development of nanotechnology, new types of fluorescent nanomaterials (FNMs) have been springing up in the past two decades. The nanometer scale endows FNMs with unique optical properties which play a critical role in their applications in bioimaging and fluorescence-dependent detections. However, since low selectivity as well as low photoluminescence efficiency of fluorescent nanomaterials hinders their applications in imaging and detection to some extent, scientists are still in search of synthesizing new FNMs with better properties.