TNF and brain ischemia: For example, the natural product oleanolic acid derivative, 2-cyano-3,12-dioxooleana-1, 9 (11)-dien-28-oic acid (CDDO) has been identified as a novel inhibitor of necroptosis by blocking the death receptor TNFα (Tumor Necrosis Factor) and targeting HSP90 to inhibit the phosphorylation of RIPK1 and RIPK2 in necroptotic cells during cerebral ischemia; the natural product derivative flavanone compound 6E11 is a novel potent small molecular inhibitor of RIPK1-driven necroptosis [201].