DT-2216

Product Description

An anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL) targeted protein degrader, using the proteolysis targeting chimera (PROTAC) technology, with potential pro-apoptotic, immunomodulating and antineoplastic activities. DT2216 is composed of a Bcl-XL ligand attached to a Von Hippel-Lindau (VHL) E3 ligase ligand. Upon administration of DT2216, the Bcl-XL binding moiety specifically targets and binds to Bcl-XL which is expressed on tumor-infiltrating regulatory T cells (Tregs) in the tumor microenvironment (TME) and cancer cells that are dependent on Bcl-XL for their survival, such as certain Bcl-XL-dependent T-cell malignancies. In turn, the VHL E3 ligase ligand is recruited to the endoplasmic reticulum (ER) and Bcl-XL is tagged by ubiquitin. This causes ubiquitination and proteasome-mediated degradation of Bcl-XL. The degradation of Bcl-XL leads to an inhibition of the anti-apoptotic activity of Bcl-XL and restores apoptotic processes in and causes depletion of Bcl-XL-expressing Tregs and Bcl-XL-dependent cancer cells. Reduction of Tregs may activate anti-tumor CD8-positive-mediated immune responses. This leads to the inhibition of tumor growth. Bcl-XL, a protein belonging to the Bcl-2 family, plays an important role in the negative regulation of apoptosis. Their expression in tumors is associated with increased Tregs survival. Tregs play a key role in cancer progression and tumor immunosuppression. Compared to other Bcl-XL inhibitors, DT2216 does not cause platelet toxicity as the VHL E3 ligase is not highly expressed in platelets. (Sourced from: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/bcl-xl-proteolysis-targeting-chimera-dt2216?redirect=true)

Mechanisms of Action: BCL2 Inhibitor

Novel Mechanism: No

Modality: Small Molecule

Route of Administration: Intravenous

FDA Designation: Fast Track - Lymphoma|T-Cell Cutaneous Lymphoma|T-Cell Lymphoma|T-Cell Peripheral Lymphoma
Orphan Drug - Lymphoma|T-Cell Lymphoma *

Approval Status: Not Approved

Approved Countries: None

Approved Indications: None

Known Adverse Events: None

Company: Elizabeth Stover, MD, PhD
Company Location:
Company Founding Year: None
Additional Commercial Interests: None