IKK-IN-3 is a highly potent and selective inhibitor of IkappaB kinase 2 (IKK2 or IKKβ). It exhibits impressive inhibitory activity against IKK2 (IC50 = 19 nM), while also demonstrating significant efficacy against IKK1 (or IKKα) with an IC50 value of 400 nM.

NF-κB-IN-1 (1,6-Heptadiene-3,5-dione, 1,7-bis(3,4-dimethoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methylene]-, (1E,6E)-) is a potent NF-κB signaling pathway inhibitor. It is a 4-arylidene crucumin analogue. NF-κB-IN-1 directly inhibits IKK to block NF-κB activation. NF-κB-IN-1 effectively inhibits the viability of lung cancer cells and attenuates the clonogenic activity of A549 cells.

IKK2-IN-4(IKK2 Inhibitor VI) is a highly potent IKK-2 inhibitor with an IC50 value of 25 nM. IKK2-IN-4 inhibited the production of TNF-α in PBMC induced by LPS.

1. Flavokawain B (Flavokavain B) has potent anti-inflammatory activity, can significantly inhibit production of NO and PGE2 in LPS-induced RAW 264.7 cells. 2. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathways. 3. Flavokawain B induces apoptosis, has the potential usefulness of FKB for prevention and treatment of hormone-refractory prostate cancer in an adjuvant setting. 4. Flavokawain B acts through ROS generation and GADD153 up-regulation to regulate the expression of Bcl-2 family members, thereby inducing mitochondrial dysfunction and apoptosis in HCT116 cells.

(±)-Nutlin-3 blocks the interaction of p53 with its negative regulator Mdm2 (IC50 = 90 nM), inducing the expression of p53-regulated genes and blocking the growth of tumor xenografts in vivo. CAY10682 is a pyrrolo[3,4c]pyrazole derivative that inhibits the p53-Mdm2 interaction as potently as (±)-nutlin-3 (Ki = 83 nM) and also dose-dependently reduces activation of the NF-κB pathway. It specifically prevents phosphorylation of IκBα by the kinases IKKα, IKKβ, and IKK (IC50s = 80.5, 78.2, and 57.1 μM, respectively). CAY10682 blocks the growth of cancer cells in vitro (IC50s = 2-6 μM) and inhibits the growth of A549 cell xenografts in mice without significantly reducing body weight.

TD1092, a pan-IAP degrader, effectively degrades cIAP1, cIAP2, and XIAP, catalyzing the activation of Caspase 3/7 and fostering apoptosis in cancer cells through IAP degradation. It also obstructs the TNFα-mediated NF-κB pathway, diminishing the phosphorylation of IKK, IkBα, p65, and p38, and operates as a PROTAC. This compound is utilized in cancer research [1].