ikk in 1

IKK-IN-1 is an inhibitor of IKK ([Ikappa]B kinase), a protein known to regulate the NF-[kappa]B signaling pathway.

1. Pristimerin (Celastrol methyl ester) has anticancer activity , treatment with Pristimerin may be a potential strategy for the suppression of hypoxia-induced metastasis through the reversal of hypoxia-induced stem cell characteristics and EMT in cancer cells. 2. Pristimerin down-regulates the expression of pro-inflammatory mediators through blocking of NF-κB activation by inhibiting interconnected ROS IKK NF-κB signaling pathways, can effectively inhibit both arthritic inflammation and cartilage and bone damage in the joints.

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.

TBK1 IKKε-IN-5 is a dual TBK1 and IKKε inhibitor(IC50 of 1 nM and 5.6 nM, respectively).

TBK1 IKKε-IN-1 is a dual inhibitor of TBK1 and IKKε with IC50 values of less than 100 nM.

TBK1 IKKε-IN-2 is a dual inhibitor of TBK1 and IKKε.

Avenanthramide-C methyl ester inhibits NF-κB activation by blocking the phosphorylation of IKK and IκB (IC50 ~ 40 μM), thereby dose-dependently inhibiting the expression and secretion of IL-6, IL-8, and MCP-1 in human aortic endothelial cells.

1,3,5-Trihydroxy-4-prenylxanthone is a relatively potent inhibitor of phosphodiesterase type 5 (PDE5) with an IC50 of 3.0 μM; it exhibits in vitro inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 56.3plusmn;0.4 and 46.0plusmn;0.3 M, respectively. It also inhibits LPS-induced NF-κB and AP-1 activations by interfering with the posttranslational modification (phosphorylation and or ubiquitinylation) of IRAK-1, disrupting TAK1-mediated activation of IKK and MAPKs signal transduction.

1. Desmethoxyyangonin (5,6-Dehydrokavain) protects LPS or LPS D-GalN-induced damages in cell or liver tissues mainly through de-regulating IKK NFκB and Jak2 STAT3 signaling pathways. 2. The induction of CYP3A23 by dihydromethysticin and Desmethoxy yangonin involves transcription activation, probably through a PXR-independent or PXR-involved indirect mechanism.

IKK-IN-4 is a potent and selective inhibitor of IkappaB kinase 2 with IC50 values of 45 nM against IKKβ and 650 nM against IKKα [1].

IKKβ-IN-1 is a potent, orally active inhibitor of IkappaB (IKK-β) with an IC50 of 0.20 μM. It reduces the inhibition of PGE2 and TNF-α production in murine macrophages and protects mice from infection shock-induced death.

PF-184 is a potent, selective inhibitor of IKK-2 with an IC50 value of 37 nM, demonstrating significant selectivity over rhIKK-1, IKKi, and over 30 other tyrosine and serine threonine kinases. It is utilized in inflammation research, including studies on asthma and chronic obstructive pulmonary disease.

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].

NF-κB-IN-11 (Compound 3i) is an inhibitor of NF-κB, effectively blocking TNF-α-induced NF-κB pathway activation and nuclear translocation of NF-κB, alongside reducing expression levels of phospho-IKK, IκBα, and NF-κB p65. Demonstrating anti-inflammatory properties, it mitigates dextran sulfate sodium-induced colitis in mice and exhibits a maximum tolerated dose (MTD) exceeding 1852 mg kg in acute toxicity assays when administered orally (p.o.) [1].

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.

Protosappanin A (PTA) has anti-oxidative nitrative activities on brain immune and neuroinflammation through regulation of CD14 TLR4-dependent IKK IκB NF-κB inflammation signal pathway; it exerts anti-neuroinflammatory effect by inhibiting JAK2-STAT3 pathway in lipopolysaccharide-induced BV2 microglia. Protosappanin A induces immunosuppression of rats heart transplantation targeting T cells in grafts via NF-kappaB pathway. Protosappanin A and protosappanin B have antimicrobial activity, they show both alone activities and resistance reversal effects of amikacin and gentamicin against MRSA. Protosappanin A shows strong effect against HIV-1 IN with an IC50 value of 12.6 uM.

[12]-Dehydrogingerdione is a natural product found in ginger that has anti-neuroinflammatory activity, possibly by inhibiting the Akt IKK IκB NF-κB pathway and promoting the Nrf-2 HO-1 pathway to prevent neuroinflammation. 12-Dehydrogingerdione can inhibit the production of NO, IL-6, and PGE2 in LPS-stimulated Raw 264.7 cells.