A series of vancomycin C-terminus guanidine modifications are disclosed that improve antimicrobial activity, enhance the durability of antimicrobial action against selection or induction of resistance, and provide two synergistic mechanisms of action independent of D-Ala-D-Ala binding that cause inhibition of cell wall biosynthesis, while inducing bacterial cell permeability. A contemplated compound contains two combined peripheral modifications, a (4-chlorobiphenyl)methyl (CBP) and C-terminus guanidine modification, that provide new treatments against not only vancomycin-sensitive, but especially vancomycin-resistant bacteria. The data demonstrate that the synergistic behavior of the peripheral modifications requires the presence of both the CBP and guanidine modifications in a single molecule versus their combined use as an equimolar mixture of singly modified compounds. A prototypical member of the series, G3-CBP-vancomycin (15), exhibits no hemolytic activity, displays no mammalian cell growth inhibition, and possesses improved and especially attractive in vivo pharmacokinetic (PK) properties.

Provided is a multi-target compound with anticoagulation and platelet GPIIb/IIIa receptor antagonism. The formula of the multi-target compound is as follows: A-L-B-L′-C. A and B are binding sites with a thrombin, C is a binding site with a platelet GPIIb/IIIa receptor, L is a first linking group, and L′ is a second linking group. Also provided are a preparation method for the compound and use of the compound. The compound has the effects on inhibiting human thrombin activity and a platelet GPIIb/IIIa receptor in vitro, and has the effects on antiplatelet aggregation in vitro/in vivo, and anticoagulation and antithrombosis in vivo.

Provided is a multi-target compound with anticoagulation and platelet GPIIb/IIIa receptor antagonism. The formula of the multi-target compound is as follows: A-L-B-L′-C. A and B are binding sites with a thrombin, C is a binding site with a platelet GPIIb/IIIa receptor, L is a first linking group, and L′ is a second linking group. Also provided are a preparation method for the compound and use of the compound. The compound has the effects on inhibiting human thrombin activity and a platelet GPIIb/IIIa receptor in vitro, and has the effects on antiplatelet aggregation in vitro/in vivo, and anticoagulation and antithrombosis in vivo.

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

A method of treating a disorder in a subject. The method comprises administering to said subject an effective amount of an agonist of the melanocortin-4 receptor (MC4R). The subject is a heterozygous carrier of an MC4R mutation, and the disorder results from an attenuated response of MC4R to a-melanocortin stimulating hormone (a-MSH).

The present application provides stable peptide-based antibody capture agents and methods of use as detection and diagnosis agents. The application further provides methods of manufacturing antibody capture agents using iterative on-bead in situ click chemistry.

The present application provides stable peptide-based antibody capture agents and methods of use as detection and diagnosis agents. The application further provides methods of manufacturing antibody capture agents using iterative on-bead in situ click chemistry.

The present disclosure provides a compound of Formula I or its stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. The present disclosure also relates to process of preparation of vancomycin-sugar conjugates of Formula I, its stereoisomers, prodrugs, pharmaceutically acceptable salts thereof, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases mediated by microbes.

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Novel antibodies and antigen binding fragments that specifically bind to KAAG1 and which may be used in the treatment, detection and diagnosis of cancer comprising KAAG1-expressing cells are disclosed herein. Cells expressing the antibodies and antigen binding fragments as well as methods of detecting and treating cancer using the antibodies and fragments are also disclosed. Cancer indications which may benefit from such treatment or detection include ovarian cancer, renal cancer, lung cancer, colorectal cancer, breast cancer, brain cancer, and prostate cancer, as well as melanomas.

The present invention provides a vancomycin derivative, and a preparation method and an application thereof. The vancomycin derivative of the present invention is obtained by introducing a glycerate moiety between a vancomycin derivative and a liposoluble modification group and has reduced liposolubility and improved water solubility, thereby reducing a side effect in the cardiovascular aspect.