There is described herein, multimers comprising a plurality of compounds covalently linked together, the compounds independently being of formula (I). ##STR00001##

There is described herein, multimers comprising a plurality of compounds covalently linked together, the compounds independently being of formula (I). ##STR00001##

The present disclosure provides novel polypeptide conjugates. The polypeptide conjugates disclosed herein comprise a stapled peptide comprising a peptide and at least one staple which holds the peptide in an α-helical conformation, and a cyclic cell-penetrating peptide (cCPP) conjugated, directly or indirectly, to the stapled peptide. The present disclosure demonstrates that cCPPs can be used to confer consistent cell-permeability to stapled peptides.

The present disclosure provides methods for site-selectively crosslinking payloads to antibodies and other proteins. This can be accomplished using traceless affinity labels designed to label target proteins with bio-orthogonally reactive entities (ORE) using the compositions and methods described herein.

The invention provides compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12D mutant of Kirsten rat sarcoma (K-Ras) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

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The invention provides compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12D mutant of Kirsten rat sarcoma (K-Ras) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

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Absorbent structures for absorbent articles are provided. The absorbent structure includes an absorbent layer with absorbent material supported by a supporting sheet, and a channel that is free of said absorbent material. The channel has a wet integrity of at least 20%.

Absorbent structures for absorbent articles are provided. The absorbent structure includes an absorbent layer with absorbent material supported by a supporting sheet, and a channel that is free of said absorbent material. The channel has a wet integrity of at least 20%.

The present disclosure provides novel polypeptide conjugates. The polypeptide conjugates disclosed herein comprise a stapled peptide comprising a peptide and at least one staple which holds the peptide in an α-helical conformation, and a cyclic cell-penetrating peptide (cCPP) conjugated, directly or indirectly, to the stapled peptide. The present disclosure demonstrates that cCPPs can be used to confer consistent cell-permeability to stapled peptides.

The present disclosure relates to imaging and endoradiotherapy of diseases involving chemokine receptor 4 (CXCR4). Provided are compounds which bind or inhibit CXCR4 and furthermore carry at least one moiety which is amenable to labeling. Provided are also medical uses of such compounds.