leukadherin-1

Leukadherin-1 (LA-1, LA1) is a first-in-class, small molecule allosteric agonist of the leukocyte integrin CD11b/CD18 (also known as Mac-1, CR3, or αMβ2). Discovered at Rush University Medical Center and initially developed by Adhaere Pharmaceuticals (later acquired by Gossamer Bio), leukadherin-1 binds to an allosteric pocket in the αA-domain of CD11b, stabilizing it in an active conformation. This activation enhances CD11b-dependent cell adhesion to its ligands (such as ICAM-1 and fibrinogen), which prevents leukocyte transendothelial migration and tissue extravasation, thereby reducing inflammatory tissue injury. The choline salt form of leukadherin-1, known as GB1275 (formerly ADH-503), was evaluated in a Phase 1/2 clinical trial for advanced solid tumors (including pancreatic adenocarcinoma and colorectal cancer) as monotherapy and in combination with pembrolizumab or chemotherapy. However, Gossamer Bio discontinued the clinical development of GB1275 in August 2021 due to lack of clinical benefit. Preclinical research continues to investigate leukadherin-1 for inflammatory and autoimmune conditions such as sepsis and lupus nephritis.

Other names

(Z)-Leukadherin-1 cholineleukadherin-1 cholineleukadherin1 cholineleukadherin 1 cholineleukadherin-1 choline saltleukadherin1 choline saltleukadherin 1 choline salt