Disclosed herein is a chemical delivery system having: i) a cargo compound comprising a first reactive moiety covalently bonded to a first enrichment moiety and a tethered cargo moiety, wherein the first reactive moiety is bonded to the tethered cargo moiety via a cleavable linker; and ii) a trigger compound comprising a second reactive moiety covalently bonded to a second enrichment moiety and a cargo-releasing moiety. The first enrichment moiety and the second enrichment moiety cause an increase in concentration of the cargo compound and the concentration of the trigger compound at a target site, causing a bimolecular reaction between the first reactive moiety and the second reactive moiety to form a cyclization precursor compound. The cargo moiety is then released from the cyclization precursor compound in a unimolecular cyclization reaction. Methods for treating conditions such as cancer, inflammatory conditions, and infections with the chemical delivery systems are also described.

Disclosed are chemical entities which are compounds of formula (I):

##STR00001##

or pharmaceutically acceptable salts thereof; wherein Y, R.sup.a, R.sup.a′, R.sup.b, R.sup.c, X.sub.1, X.sub.2, X.sub.3, R.sup.d, Z.sub.1, and Z.sub.2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I):

##STR00001##

or a stereoisomer, tautomer or salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, L.sup.1, L.sup.2, L.sup.3, L.sup.4, M, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

Disclosed herein are 3, 4-didehydro- and 3′-deoxy-3, 4-didehydro-compounds and pharmaceutical compositions thereof. Methods of use of these pharmaceutical compositions include those for treating diseases including virus-induced diseases, cancer, autoimmune diseases, immune disorders, and bacterial-associated diseases or infections, or combinations thereof. Examples of viral-induced diseases include viral infections by RNA or DNA viruses, for example SAR-CoV-2, EBV, BKV, JCV and HCMV.

The present invention relates to a compound of formula (I), a method for using the compound as an EGFR inhibitor, and a pharmaceutical composition comprising the compound. The compound can be used for treatment, prevention or alleviation of diseases or disorders such as cancer or infection.

##STR00001##

The present invention relates to a compound of formula (II) or (IIb) Wherein X, Y, R.sup.x, R.sup.y, R.sup.5 and Nu are as defined in the description and in the claims. The compound of formula (II) can be used in the manufacture of oligonucleotides. ##STR00001##

The invention provides compounds of the formula:

##STR00001## R.sup.1 is OR.sup.11, or NR.sup.5R.sup.5′; R.sup.2 is H or F; R.sup.5 is H, C.sub.1-C.sub.6alkyl, OH, C(═O)R.sup.6, O(C═O)R.sup.6 or O(C═O)OR.sup.6; R.sup.5′ is H or C.sub.1-C.sub.6alkyl; R.sup.6 is C.sub.1-C.sub.6or C.sub.3-C.sub.7cycloalkyl; R.sup.13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R.sup.22;

and the other variables are as defined in the claims,

which are of use in the treatment of cancer, and related aspects.

Disclosed herein are therapeutic compounds capable of targeting abroad range of tumor cells. The present disclosure is further directed to compositions comprising the therapeutic compounds, methods of manufacturing the therapeutic compounds, and methods of treating cancer comprising administering the therapeutic compounds.

The present invention provides cromakalim prodrugs, compositions, and their use for the modulation of ATP-sensitive potassium (K.sub.ATP) channels for therapeutic purposes.

The invention relates to compositions of nicotinamide mononucleotide derivatives and their methods of use. The invention also relates to methods of preparing nicotinamide mononucleotide derivatives. The invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinamide mononucleotide derivative. The invention relates to methods of using nicotinamide mononucleotide derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases and improving cell and tissue survival.