GB111-NH2

GB111-NH2 is a small molecule, broad-spectrum inhibitor of cysteine cathepsins, a family of proteases that are frequently upregulated in various cancers to facilitate tumor invasion and metastasis. In hematological malignancies such as diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), GB111-NH2 has been shown to significantly reduce cathepsin activity, leading to increased apoptosis and caspase-3 activation. Beyond its activity as a standalone agent in preclinical models, GB111-NH2 serves as the structural basis for payloads in antibody-drug conjugates (ADCs). For instance, a maleimide-modified version (M-GB) can be conjugated to antibodies targeting CD74, allowing for the selective delivery of the cathepsin inhibitor to malignant B cells while minimizing systemic toxicity and potentially overcoming rituximab resistance.