The present disclosure provides compositions and methods for improving an antitumor response against non-inflamed solid tumors. Methods of this disclosure include use of an eIF4A inhibitor to promote infiltration of antitumor lymphocytes into a non inflamed solid tumor. Methods of treating cancer associated with a non-inflamed solid tumor are also provided.

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula:

##STR00001##

where A, B, R.sub.1, X.sub.1, X.sub.2, and W are described herein.

The invention provides compounds of Formula (A) that may inhibit ENPP1, and that are accordingly useful for treatment of disorders related to ENPP1. The invention further provides pharmaceutical compositions containing these compounds and methods of using these compounds to treat or prevent disorders related to ENPP1. ##STR00001##

Reversibly cross-linkable foam is provided. The reversibly cross-linked foam includes a first polymeric material, at least one reversibly cross-linkable monomer polymerized with the first polymeric material, and at least one blowing agent. The reversibly cross-linkable co-polymeric foam is thermally stable at temperatures of at least 10 degrees higher than otherwise identical polymeric foam that does not include the reversibly cross-linkable agent polymerized with the first polymeric material.

Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively ##STR00001##
wherein, R.sub.1 and R.sub.2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR.sub.3R.sub.4, OR.sub.5, or SR.sub.5, where R.sub.3 and R.sub.4 are individually selected from acyl or sulfonyl, and where R.sub.5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively ##STR00001##
wherein, R.sub.1 and R.sub.2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR.sub.3R.sub.4, OR.sub.5, or SR.sub.5, where R.sub.3 and R.sub.4 are individually selected from acyl or sulfonyl, and where R.sub.5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

The present invention relates to compounds, and pharmaceutically acceptable compositions thereof, useful as antagonists of IDO, and for the treatment of IDO-related disorders.

The present invention relates to compounds, and pharmaceutically acceptable compositions thereof, useful as antagonists of IDO, and for the treatment of IDO-related disorders.

This invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides compounds that inhibit Aurora kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer.