The present invention provides a genus of polycyclic amines that are useful as opioid receptor modulators. The compounds of the invention are useful in both therapeutic and diagnostic methods, including for treating pain, neurological disorders, cardiac disorders, bowel disorders, drug and alcohol addiction, drug overdose, urinary disorders, respiratory disorders, sexual dysfunction, psoriasis, graft rejection or cancer.

Binding of the transcriptional co-activator, YAP1, to the transcription factor Oct4, induces Sox2, which is a transcription actor necessary for the self-renewal of stem-like cells from non-small cell lung cancer. The WW domain of YAP1 binds to the PPxY motif of Oct4 to induce Sox2. Delivering a peptide corresponding to the WW domain could prevent the induction of Sox2 and stemness. Similarly, peptides and mimetics of the PPxY motif would be able to inhibit sternness. Disclosed are compounds that affect the Yap1:Oct4 interaction.

The present technology relates to compounds of any one of Formula I, II, IIa, III, IV, and/or V as described herein and their tautomers and/or pharmaceutically acceptable salts, compositions, and methods of uses thereof.

The present technology relates to compounds of any one of Formula I, II, IIa, III, IV, and/or V as described herein and their tautomers and/or pharmaceutically acceptable salts, compositions, and methods of uses thereof.

The use of glutamate 2b receptor antagonists and sigma receptor agonists as antitussives to treat or prevent a cough is disclosed. In preferred embodiments, the glutamate 2b receptor antagonist is ifenprodil or radiprodil. Preferred sigma receptor agonists include fluvoxamine, fluoxetine, excitalpram, and donepezil.

Provided herein are ionizable lipids represented by the Formula (I): or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.1′, R.sup.2′, R.sup.3′, R.sup.4′, R.sup.5′, R.sup.6′, m, and n are as defined herein. Also provided herein are lipid nanoparticle (LNP) compositions comprising an ionizable lipid of the invention and a capsid-free, non-viral vector (e.g., ceDNA). These LNPs can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest (e.g., cell, tissue, organ, and the like).

##STR00001##

Methods of analyzing a drug polypeptide conjugate using tandem mass spectrometry involving dual tandem mass tags (TMTs) are described. Provided herein is an integrated method using TMTs to obtain three analytical measurements, termed “triple play”, which enables identification of the drug occupancy, normalization between multiple samples and triggering of additional MS/MS to identify and localize conjugation site(s) of the payload. Also described is a method of multiplexing conjugation reactions in a single run with TMT labeling for enhanced throughput capability, while maintaining the same sensitivity with current mass spectrometry instrumentation.

A compound is represented by formula I. A stereoisomer, tautomer, solvate, polymorph of the compound or a pharmaceutically acceptable salt of the compound, a pharmaceutical composition containing the compound, a preparation method of the compound, and the medical use of the compound are provided.

##STR00001##

A compound is represented by formula I. A stereoisomer, tautomer, solvate, polymorph of the compound or a pharmaceutically acceptable salt of the compound, a pharmaceutical composition containing the compound, a preparation method of the compound, and the medical use of the compound are provided.

##STR00001##

The present invention provides a genus of polycyclic amines that are useful as opioid receptor modulators. The compounds of the invention are useful in both therapeutic and diagnostic methods, including for treating pain, neurological disorders, cardiac disorders, bowel disorders, drug and alcohol addiction, drug overdose, urinary disorders, respiratory disorders, sexual dysfunction, psoriasis, graft rejection or cancer.