The present disclosure concerns inhibitors of Norovirus protease that are suitable for use against any genotype of Norovirus, including at least GII.4 Norovirus proteases. In particular embodiments, specific compositions are encompassed, including their use for prevention or treatment of Norovirus infection in an individual.

[Problem] To provide a fluorescent probe capable of detecting pancreatic cancer specifically.

[Solution] A fluorescent probe for use in the detection of pancreatic cancer, which comprises a compound represented by general formula (I) or a salt thereof.

##STR00001##

Disclosed are conjugates including a recognition element covalently bonded to or linked through a linker to a payload. The payload is a pharmaceutical agent (e.g., an antineoplastic agent, anti-infective agent, or anti-inflammatory agent) or a diagnostic agent. Also disclosed are methods of using the conjugates.

The disclosure relates to bifunctional KRAS-modulating compounds having the structure K-L-T, where K is a targeting group that binds specifically to a KRAS protein (mutant or wild-type), T is an E3-ligase binding group, and L is absent or is a bivalent linking group that connects K and T together via a covalent linkage. Compounds and pharmaceutical compositions thereof can promote degradation of KRAS protein (mutant or wild-type) in a cell and are thus useful for treating, inhibiting, and preventing KRAS-associated diseases, disorders and conditions, including cancers.

The present invention relates to novel amide derivatives of N-urea substituted amino acids, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.

A fluorescent probe that detects calpain enzyme activity with high sensitivity, wherein, enzymatic reactivity with a calpain is improved by bonding an amide group having ?-carbon, which is bonded to an oxygen atom, to the N-terminal of a peptide chain. A fluorescent probe detects calpain activity with higher sensitivity because the probe is improved in reactivity with a calpain as compared to a HMRG fluorescent probe that has heretofore been reported. Specifically, the fluorescent probe relates to a compound represented by the following general formula (I) or a salt thereof.

##STR00001##

The present invention relates to novel amide derivatives of N-urea substituted amino acids, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.

The present invention is based on the discovery of a proteolysis targeting compound having tissue targeting capability and use thereof, relating to medicinal products, and to such a compound or a pharmaceutically acceptable salt thereof, a stereoisomer, a solvate, or a polymorph. The compound is a proteolysis targeting chimera (PROTAC) with specific tissue targeting ability. The compound structure comprises three parts, i.e., A-BD-CON, wherein the part A is a PROTAC, one end of the structure thereof is a target protein binding ligand, and the other end is a ubiquitin ligase ligand; and the part CON is a ligand of an asialoglycoprotein receptor (ASGPR), enabling the specific tissue targeting function. The compound enriches in liver tissue and is able to target cells in the tissue. The invention achieves improved druggability of the PROTAC with higher solubility and cellular membrane permeability, therefore produces enhanced pharmaceutical effect on the specific target tissue.

Disclosed are a compound-linker conjugate and a class of compounds having the STING activation activity, as well as their applications in the preparation of antibody drug conjugates. The compound-linker conjugate is represented by

##STR00001##

The compounds are represented by

##STR00002##

The compounds are suitable as payloads of the antibody drug conjugates.

The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions of at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.