GFB-12811

GFB-12811 is a selective small molecule inhibitor of Cyclin-dependent kinase 5 (CDK5). Originally developed by Goldfinch Bio for the treatment of kidney diseases, specifically targeting podocyte health, it has more recently been investigated for its potential in oncology. In Mantle Cell Lymphoma (MCL), CDK5 is frequently upregulated in cells that have developed resistance to Bruton tyrosine kinase inhibitors (BTKIs) like ibrutinib. GFB-12811 works by inhibiting CDK5, which in turn disrupts the IRE1α/Xbp1s axis of the Unfolded Protein Response (UPR) pathway. This mechanism has been shown to reduce the proliferation of resistant MCL cells and partially abrogate BTKI resistance, suggesting its utility as a therapeutic strategy for patients with relapsed or refractory MCL.