Therapeutic Target Identification and Drug Discovery Driven by Chemical Proteomics.

Throughout the human lifespan, from conception to the end of life, small molecules have an intrinsic relationship with numerous physiological processes. The investigation into small-molecule targets holds significant implications for pharmacological discovery. The determination of the action sites of small molecules provide clarity into the pharmacodynamics and toxicological mechanisms of small-molecule drugs, assisting in the elucidation of drug off-target effects and resistance mechanisms. Consequently, innovative methods to study small-molecule targets have proliferated in recent years, with chemical proteomics standing out as a vanguard development in chemical biology in the post-genomic age. Chemical proteomics can non-selectively identify unknown targets of compounds within complex biological matrices, with both probe and non-probe modalities enabling effective target identification. This review attempts to summarize methods and illustrative examples of small-molecule target identification via chemical proteomics. It delves deeply into the interactions between small molecules and human biology to provide pivotal directions and strategies for the discovery and comprehension of novel pharmaceuticals, as well as to improve the evaluation of drug safety.

Ultra-low-loss 5-LP mode selective coupler based on fused biconical taper technique.

Trapped in the stringent adiabatic transmission condition of high-order modes, low-loss fused biconical taper mode selective coupler (FBT-MSC) has long been challenging to achieve. We identify the adiabatic predicament of high-order modes to stem from the rapid variation of the eigenmode field diameter, which is caused by the large core-cladding diameter difference of few-mode fiber (FMF). We demonstrate that introducing a positive-index inner cladding in FMF is an effective approach to address this predicament. The optimized FMF can be used as dedicated fiber for FBT-MSC fabrication, and exhibits good compatibility with the original fibers, which is critical for the wide adoption of MSC. As an example, we add inner cladding in a step-index FMF to achieve excellent adiabatic high-order mode characteristics. The optimized fiber is used to manufacture ultra-low-loss 5-LP MSC. The insertion losses of the fabricated LP01, LP11, LP21, LP02 and LP12 MSCs are 0.13 dB at 1541 nm, 0.02 dB at 1553 nm, 0.08 dB at 1538 nm, 0.20 dB at 1523 nm, and 0.15 dB at 1539 nm, respectively, with smoothly varying insertion loss across the wavelength domain. Additional loss is less than 0.20 dB from 1465.00 nm to 1639.31 nm, and the 90% conversion bandwidth exceeds 68.03 nm, 166.68 nm, 174.31 nm, 132.83 nm, and 84.17 nm, respectively. MSCs are manufactured using commercial equipment and a standardized process that takes just 15 minutes, making them a potential candidate for low-cost batch manufacturing in a space division multiplexing system.