HETEROCYCLIC CONJUGATES AND THEIR USES

Claims

This description provides pharmaceutically acceptable compounds and salts thereof, and methods for their use. The compounds and methods have a variety of applications as therapeutic, diagnostic, and research tools. In particular, the compositions and methods in question are useful for reducing the signaling output of oncogenic proteins.

1. A conjugate comprising an antigen-binding unit exhibiting binding specificity for at least one non-KRAS prime antigen, wherein the antigen-binding unit is covalently linked to a small-molecule KRAS inhibitor, optionally via a chemical linker, and wherein the antigen-binding unit and the KRAS inhibitor in the conjugate synergistically inhibit the signaling output of the prime antigen and KRAS.

2. A conjugate comprising an antigen-binding unit exhibiting binding specificity for at least one non-KRAS prime antigen, wherein the antigen-binding unit is covalently linked to a small-molecule KRAS inhibitor, optionally via a chemical linker, and wherein the KRAS inhibitor selectively inhibits KRAS or a mutant thereof with respect to HRAS and NRAS.

7. A conjugate of formula (A), wherein: AgB is an antigen-binding unit; L is a chemical linker; D is independently selected from each occurrence of a small-molecule KRAS inhibitor, a small-molecule cytotoxic agent, and a small-molecule agent that selectively modulates a non-KRAS target, wherein at least one D is a KRAS inhibitor; p is selected from 1 to 20; and q is selected from 1 to 20.

58. A pharmaceutical composition comprising the conjugate of any one of claims 1 to 57, or a salt thereof, and a pharmaceutically acceptable excipient.