Abstract: The present disclosure provides a compound of Formula (I?), or a pharmaceutically acceptable salt thereof and its use in, e.g. treating a condition, disease, or disorder in which lowering mutant huntingtin protein (“mHTT”) in a subject is of therapeutic benefit, specifically in treating Huntington disease (“HD”). This disclosure also features a composition containing the same as well as methods of using and making the same.

Abstract: This disclosure relates to compounds of Formula (A): Formula (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; Formula (I) in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.

Abstract: This disclosure relates to compounds of Formula (A): IRAK-L-DSM (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.

Abstract: This disclosure relates to compounds of Formula (A): BTK-L-DSM (A) or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches BTK to DSM, and BTK is a Btk binding moiety represented by Formula (I) or Formula (II) that is covalently attached to linker L: in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of Btk proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of Btk proteins. The present disclosure also provides methods of treating disorders responsive to modulation of Btk activity and/or degradation of Btk with at least one compound described herein.

Abstract: The present invention includes CSNK1A1 inhibitors that are useful in treating or preventing a cancer in a subject. In certain embodiments, the cancer comprises a hematological cancer, such as but not limited to acute myeloid leukemia (AML) and/or MDS (myelodysplastic syndrome, including 5q-MDS). In other embodiments, the cancer comprises colon cancer.

Abstract: The application relates to substituted hydantoinamides of formula (I) as ADAMTS7 antagonists, to processes for their preparation, their use alone or in combination for the treatment or prophylaxis of diseases, in particular of cardiovascular diseases, including atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), arterial occlusive disease or restenosis after angioplasty. R1 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, 5- to 6-membered heteroaryl or phenyl; R2 is hydrogen or alkyl; A is 5-membered heteroaryl; Z is 6- to 10-membered aryl or 5- to 10-membered heteroaryl; all groups being optionally substituted.

Abstract: The present invention includes CSNK1A1 inhibitors that are useful in treating or preventing a cancer in a subject. In certain embodiments, the cancer comprises a hematological cancer, such as but not limited to acute myeloid leukemia (AML) and/or MDS (myelodysplastic syndrome, including 5q-MDS). In other embodiments, the cancer comprises colon cancer.

Abstract: The present disclosure provides compounds of Formula (I?), Formula (I), Formula (II), Formula (II-A), Formula (III), and Formula (IV). The compounds described herein are MAX binders and/or modulators of Myc, Mad, or Mxi1 (e.g., inhibitors of Myc, Mad, or Mxi1), and may be useful in treating a subject with a disease associated with Myc, such as proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions and kits including the compounds described herein, as well as methods of using and uses of the compounds, compositions, and kits.

Abstract: The present disclosure provides compounds of Formula (I-a), Formula (I), and Formula (II). The compounds described herein may be Myc modulators (e.g., Myc inhibitors) and may be useful in treating in a subject in need thereof diseases associated with Myc and proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including a compound described herein.

Abstract: The present disclosure provides compounds of Formula (I?), Formula (I), Formula (II), Formula (II-A), Formula (III), and Formula (IV). The compounds described herein are MAX binders and/or modulators of Myc, Mad, or Mxi1 (e.g., inhibitors of Myc, Mad, or Mxi1), and may be useful in treating a subject with a disease associated with Myc, such as proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions and kits including the compounds described herein, as well as methods of using and uses of the compounds, compositions, and kits.

Abstract: The present disclosure provides compounds of Formula (I?), Formula (I), Formula (II), Formula (II-A), Formula (III), and Formula (IV). The compounds described herein are MAX binders and/or modulators of Myc, Mad, or Mxi1 (e.g., inhibitors of Myc, Mad, or Mxi1), and may be useful in treating a subject with a disease associated with Myc, such as proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions and kits including the compounds described herein, as well as methods of using and uses of the compounds, compositions, and kits.

Abstract: The present disclosure provides compounds of Formula (I-a), Formula (I), and Formula (II). The compounds described herein may be Myc modulators (e.g., Myc inhibitors) and may be useful in treating in a subject in need thereof diseases associated with Myc and proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including a compound described herein.

Abstract: The present disclosure provides compounds of Formula (I-a), Formula (I), and Formula (II). The compounds described herein may be Myc modulators (e.g., Myc inhibitors) and may be useful in treating in a subject in need thereof diseases associated with Myc and proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including a compound described herein.

Abstract: The present disclosure provides compounds of Formula (I?), Formula (I), Formula (II), Formula (II-A), Formula (III), and Formula (IV). The compounds described herein are MAX binders and/or modulators of Myc, Mad, or Mxi1 (e.g., inhibitors of Myc, Mad, or Mxi1), and may be useful in treating a subject with a disease associated with Myc, such as proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions and kits including the compounds described herein, as well as methods of using and uses of the compounds, compositions, and kits.

Abstract: The present disclosure provides compounds of Formula (I-a), Formula (I), and Formula (II). The compounds described herein may be Myc modulators (e.g., Myc inhibitors) and may be useful in treating in a subject in need thereof diseases associated with Myc and proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including a compound described herein.