KIN-8194 is an orally active dual inhibitor of HCK and BTK , with IC 50 values of 0.915 and <0.495 nM, respectively. KIN-8194 impairs growth and integrin-mediated adhesion of BTKi-resistant mantle cell lymphoma (MCL). KIN-8194 overcomes ibrutinib resistance with a survival benefit in TMD-8 ABC DLBCL xenografted mice.