The invention relates to stable, isotopically labeled variants of methotrexate for use in mass spectrometry analysis for quantifying methotrexate in a sample. The compounds have the structure wherein each of Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5, Y.sub.6, Y.sub.7, Y.sub.8, Y.sub.9, Y.sub.10, Y.sub.11<Y.sub.12-Y.sub.13 and Y.sub.14 is independently selected from carbon or carbon-13; and wherein at least 5 of Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5, Y.sub.6, Y.sub.7, Y.sub.8, Y.sub.9, Y.sub.10, Y.sub.11, Y.sub.12, Y.sub.13 and Y.sub.14 are carbon-13.

##STR00001##

The invention relates to stable, isotopically labeled variants of methotrexate for use in mass spectrometry analysis for quantifying methotrexate in a sample. The compounds have the structure wherein each of Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5, Y.sub.6, Y.sub.7, Y.sub.8, Y.sub.9, Y.sub.10, Y.sub.11<Y.sub.12-Y.sub.13 and Y.sub.14 is independently selected from carbon or carbon-13; and wherein at least 5 of Y.sub.1, Y.sub.2, Y.sub.3, Y.sub.4, Y.sub.5, Y.sub.6, Y.sub.7, Y.sub.8, Y.sub.9, Y.sub.10, Y.sub.11, Y.sub.12, Y.sub.13 and Y.sub.14 are carbon-13.

##STR00001##

Described herein are novel divalent nucleobases that each bind two nucleic acid strands, matched or mismatched when incorporated into a nucleic acid or nucleic acid analog backbone (a genetic recognition reagent, or genetic recognition reagent). In one embodiment, the genetic recognition reagent is a peptide nucleic acid (PNA) or gamma PNA (PNA) oligomer. Uses of the divalent nucleobases and monomers and genetic recognition reagents containing the divalent nucleobases also are provided.

Described herein are novel divalent nucleobases that each bind two nucleic acid strands, matched or mismatched when incorporated into a nucleic acid or nucleic acid analog backbone (a genetic recognition reagent, or genetic recognition reagent). In one embodiment, the genetic recognition reagent is a peptide nucleic acid (PNA) or gamma PNA (PNA) oligomer. Uses of the divalent nucleobases and monomers and genetic recognition reagents containing the divalent nucleobases also are provided.

A method for treating a p62-mediated disease (e.g., multiple myeloma) in a subject, the method comprising administering to the subject a therapeutically effective amount of at least one p62-ZZ inhibitor compound.

A method for treating a p62-mediated disease (e.g., multiple myeloma) in a subject, the method comprising administering to the subject a therapeutically effective amount of at least one p62-ZZ inhibitor compound.

Described herein are divalent nucleobases that each binds two nucleic acid strands, matched or mismatched when incorporated into a nucleic acid or nucleic acid analog backbone, such as in a -peptide nucleic acid (PNA). Also provided are genetic recognition reagents comprising one or more of the divalent nucleobases and a nucleic acid or nucleic acid analog backbone, such as a PNA backbone. Uses for the divalent nucleobases and monomers and genetic recognition reagents containing the divalent nucleobases also are provided.

Described herein are divalent nucleobases that each binds two nucleic acid strands, matched or mismatched when incorporated into a nucleic acid or nucleic acid analog backbone, such as in a -peptide nucleic acid (PNA). Also provided are genetic recognition reagents comprising one or more of the divalent nucleobases and a nucleic acid or nucleic acid analog backbone, such as a PNA backbone. Uses for the divalent nucleobases and monomers and genetic recognition reagents containing the divalent nucleobases also are provided.

The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.

The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.