In the preclinical setting, inhibitors of histone deacetylase 6 (HDAC6) have proven effective at reducing liver inflammation through modulation of the immune response.

Immune checkpoint blockade is one of the major advances in cancer treatment in recent years. However, the majority of immune checkpoints are embedded in the cell membrane and this fact represents a limitation for targeted degradation using proteolysis-targeting chimeras (PROTACs).

Aromatase inhibitors (AI) are among the most widely used therapies in the treatment of breast tumors expressing estrogen receptor α (ERα). Alone or in combination with other agents, they are the standard of care for hormone receptor-positive tumors.

The protease mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) is a signaling protein with both molecular scaffolding and protease activity involved in lymphocyte activation. MALT1 is considered a therapeutic target for chronic lymphocytic leukemia (CLL) in patients who develop resistance to Bruton tyrosine kinase (BTK) inhibitors.

Researchers from AUTOTAC Bio Inc. and affiliated organizations presented preclinical data for ATC-324, a novel autophagy-targeting chimera (AUTOTAC) designed to induce androgen receptor (AR) degradation.

Interleukin-1 receptor-associated kinase 4 is critical in the modulation of inflammatory responses through Toll-like receptor and IL-1R signaling.

The transcription factor IKZF2 is a marker of highly suppressive regulatory T cells (Tregs). When IKZF2 is degraded, Tregs become effector-like T cells leading to increased antitumor immune response in the tumor microenvironment.

Data from preclinical studies conducted to evaluate the activity of NKT-3964, a first-in-class, orally bioavailable CDK2-selective PROTAC degrader being developed for the potential treatment of cancer, were reported by Nikang Therapeutics Inc.

Two days after Monte Rosa Therapeutics Inc. signed a molecular glue degrader deal with Novartis AG, two other companies, Biogen Inc. and Neomorph Inc., are moving forward in the same space in a partnership worth up to $1.45 billion. Cambridge, Mass.-based Biogen and San Diego-based Neomorph will develop molecular glue degraders (MGDs) for priority targets in Alzheimer’s, rare neurological and immunological diseases, using Neomorph’s MGD platform to identify and validate novel small-molecule protein degraders.