The disclosure relates generally to polyglutamated alpha tetrahydrofolate compositions, including delivery vehicles such as liposomes containing the polyglutamated alpha tetrahydrofolate, and methods of making and using the polyglutamated alpha tetrahydrofolate compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis). The disclosed compositions also have uses in combination therapy with one or more therapeutic agents to enhance the effectiveness or to reduce the toxicities associated with the therapeutic agent(s).

The present invention relates to novel antifolate linker-drugs, conjugates comprising such antifolate linker-drugs, and the use thereof in the treatment of diseases, such as cancer, autoimmune and infectious diseases, optionally in combination with other therapeutic agents.

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 (γPNA) 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 (γPNA) oligomer. Uses of the divalent nucleobases and monomers and genetic recognition reagents containing the divalent nucleobases also are provided.

The disclosure relates to aryl hydrocarbon receptor antagonists as well as methods of modulating aryl hydrocarbon receptor activity and expanding hematopoietic stem cells by culturing hematopoietic stem or progenitor cells in the presence of these agents. Additionally, the disclosure provides methods of treating various pathologies, such as cancer, by administration of these aryl hydrocarbon receptor antagonists. Additionally, the disclosure provides methods of treating various pathologies in a patient by administration of expanded hematopoietic stem cells. The disclosure further provides kits containing aryl hydrocarbon receptor antagonists that can be used for the expansion of hematopoietic stem cells. The disclosure further relates to pharmaceutical compositions comprising the compounds and methods of treating or preventing a disease in which aryl hydrocarbon receptor plays a role.

The disclosure relates generally to alpha polyglutamated methotrexate, formulations containing liposomes filled with alpha polyglutamated methotrexate, methods of making the alpha polyglutamated methotrexate and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated methotrexate and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

The disclosure relates generally to gamma polyglutamated methotrexate compositions, including delivery vehicles such as liposomes containing the gamma polyglutamated methotrexate, and methods of making and using the gamma polyglutamated methotrexate compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis).

The disclosure relates generally to gamma polyglutamated pemetrexed compositions, including delivery vehicles such as liposomes containing the gamma polyglutamated pemetrexed, and methods of making and using the gamma polyglutamated pemetrexed compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e g , inflammation and autoimmune diseases such as rheumatoid arthritis).

The disclosure relates generally to gamma polyglutamated tetrahydrofolate compositions, including delivery vehicles such as liposomes containing the gamma polyglutamated tetrahydrofolate, and methods of making and using the gamma polyglutamated tetrahydrofolate compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis). The disclosed compositions also have uses in combination therapy with one or more therapeutic agents to enhance the effectiveness or to reduce the toxicities associated with the therapeutic agent(s).

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.