In this vein, we present CTLAP, a fluorogenic probe that is rapidly activated by CTL and displays good selectivity over CTB and CTV, the closest competing analytes for CTL activity probes. CTLAP exhibits intrinsically low background fluorescence, which we attribute to the notably low quantum yield measured for the probe. CTLAP demonstrates markedly higher turn-on ratios (24-fold) and moderately improved enzyme selectivity (6- to 10-fold) when compared to Z-FR-AMC (10-fold turn-on ratio, 6- to 7-fold selectivity), a commercially available CTL-selective probe commonly used to detect CTL activity in mixed samples. Optimum selectivity for CTL is achieved within 10 min of incubation with the enzyme, suggesting that CTLAP is amenable for rapid detection of CTL, even in the presence of competing cathepsins.

A class of ketoamide-based compounds, in particular, a ketoarnide-based compound as represented by general formula A is provided. The ketoamide compound may be used as a 2019 novel coronavirus (2019-nCov) 3 CL protease inhibitor and/or human cathepsin L inhibitor, and/or may be used in the preparation of a medicament for treating and/or preventing and relieving respiratory tract infection, pneumonia and other related diseases caused by 2019 novel coronavirus infection. Pharmaceutical compositions of the class of compounds, pharmaceutical salts, enantiomeric forms, diastereoisomers and racemic compounds thereof in the preparation of a medicament for treating and/or preventing and relieving respiratory tract infections and other related diseases caused by the 2019 novel coronavirus infection are also provided.

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The present invention relates to compounds of the general formula (I) having a selective FKBP51 ligand scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said selective FKBP51 ligand compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions. ##STR00001##

Provided herein are modified amino acids comprising a tetrazine groups according to Formula I: polypeptides, antibodies, payloads and conjugates comprising these modified amino acid residues derived from the modified amino acids, and methods of producing the polypeptides, antibodies, payloads and conjugates comprising the modified amino acid residues. The polypeptides, antibodies, payloads and conjugates are useful in methods of treatment and prevention, methods of detection and methods of diagnosis. ##STR00001##

The drug component of an antibody-drug conjugate having a structure according to formula (II), where Ab, m, n, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are as defined in the application, exhibits unexpectedly improved stability.

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The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

The invention relates to methods for treating depression, anxiety, and other related diseases by administering a peptide NMDAR partial agonist.

Prodrugs of an NMDA antagonist, (S)-1-phenyl-2-(pyridin-2-yl)ethanamine, useful for the treatment of depression (particularly major depressive disorder) or pain; compositions comprising them, and methods of making them.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof:

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which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable slat thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

Processes are described for the preparation of tubulysins. The processes are useful for preparing predetermined mixtures of tubulysins, preparing single tubulysins from mixtures of tubulysins, and for converting one tubulysin into a different tubulysin. The tubulysins described herein are useful in treating diseases and disease states that include pathogenic cell populations.