SHARPIN and arthritic joint disease: For example, a novel RIPK1 inhibitor, PK68, significantly suppressed the lung metastasis of melanoma cells in mice [92] The inhibition of RIPK1 in mice by knock-in inactivated RIPK1 D138N or the murine-potent inhibitor GNE684 showed no effect in reducing lung metastases of B16 melanoma cells, although it mitigated collagen antibody-induced arthritis, skin inflammation caused by mutation of Shank-associated RH domain interactor (SHARPIN, which is associated with NF-kappa-B activation and regulation of inflammation), or colitis caused by deletion of Nemo (also known as IKK-γ.