IKK Inhibitor

Oxaprozin is an orally active and potent COX inhibitor, with IC₅₀ values of 2.2 μM for human platelet COX-1 and and 36 μM for IL-1-stimulated human synovial cell COX-2, respectively. Oxaprozin also inhibits the activation of NF-κB. Oxaprozin induces cell apoptosis. Oxaprozin shows anti-inflammatory activity. Oxaprozin-mediated inhibition of the Akt/IKK/NF-κB pathway contributes to its anti-inflammatory properties.

TBK1/IKKε-IN-5 (compound 1) is an orally active TBK1 and IKKε dual inhibitor, with IC₅₀ values of 1 and 5.6 nM, respectively. TBK1/IKKε-IN-5 enhances the blockade response to PD-1 and induces immune memory in rats when combines with anti-PD-L1. TBK1/IKKε-IN-5 can be used in cancer research, especially in tumour immunity.

GS143 is a selec­tive IκBα ubiquitination inhibitor with an IC₅₀ of 5.2 μM for SCF^βTrCP1-mediated IκBα ubiquitylation. GS143 sup­presses NF-κB acti­va­tion and tran­scrip­tion of tar­get genes and does not inhibit proteasome activity. GS143 has anti-asthma effect.

TBK1-IN-1 is a potent and selective TANK binding kinase 1 (TBK1) inhibitor with an IC₅₀ value of 22.4 nM. TBK1-IN-1 inhibits TBK1 downstream target genes cxcl10 and ifnβ expression. TBK1-IN-1 has anticancer activity.

Plantainoside D, a phenylethanoid glycosides, is a IKK-β inhibitor with diverse biological activities. Plantainoside D shows inhibitory activity of angiotensin-converting enzyme (ACE) with an IC₅₀ of 2.17 mM. Plantainoside D significantly reduces the release of glutamate from nerve terminals in the cerebral cortex of rats by inhibiting the voltage-dependent calcium channel (VDCCs) and protein kinase C (PKC) signaling cascade. Plantainoside D significantly alleviates cell apoptosis by inhibiting the generation of ROS and the activation of NF-κB. Plantainoside D significantly improves acute lung injury (ALI) induced by sepsis by regulating the Sirt3/NLRP3 signaling pathway. Plantainoside D can be used for the study of neuroprotection, antioxidant, anti-inflammation, antihypertension.

PS-1145 is an IκB kinase (IKK) inhibitor with an IC₅₀ of 88 nM.

BI605906, a chemical probe, is a novel IKKβ inhibitor with an IC₅₀ value of 380 nM when assayed at 0.1 mM ATP.

ACHP Hydrochloride (IKK-2 Inhibitor VIII) is a highly potent and selective IKK-β inhibitor with an IC₅₀ of 8.5 nM.

IKK 16 hydrochloride is an orally active IKK inhibitor. IKK 16 hydrochloride shows IC₅₀s of 40 nM, 70 nM, 200 nM, and 50 nM for IKK2, IKK complex, IKK1, and LRRK 2, respectively. IKK 16 hydrochloride is also a pan-PKD inhibitor, inhibiting PKD1, PKD2, and PKD3 with IC₅₀s of 153.9, 115, and 99.7 nM, respectively. IKK 16 hydrochloride is also an ABCB1 inhibitor, interfering with the binding of ABCB1 to its substrates. IKK 16 hydrochloride protects against LPS (HY-D1056)-induced multiple organ dysfunction by reducing the acute inflammatory response induced by endotoxin exposure. IKK 16 hydrochloride can restore renal function and alleviate fibrosis in acute kidney injury. IKK 16 hydrochloride attenuates cardiac dysfunction associated with polymicrobial sepsis in mice with type 2 diabetes mellitus (T2DM) by inhibiting the NF-κB pathway.

BAY32-5915 is a potent IKKα inhibitor with an IC₅₀ value of 60 nM. BAY32-5915 has not affect Doxorubicin (HY-15142A)-induced NF-κB activation.

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

Bay 65-1942 hydrochloride is an ATP-competitive and selective IKKβ inhibitor.

NF-κB-IN-1, a 4-arylidene crucumin analogue, is a potent NF-κB signaling pathway inhibitor. 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.

HOIPIN-1 (JTP-0819958) is a selective linear ubiquitin chain assembly complex (LUBAC) inhibitor with an IC₅₀ of 2.8 μM. HOIPIN-1 suppress LUBAC-mediated NF-kB activation in vitro.

Geranial is an aromatic compound. It can be isolated from the fruits of Litsea cubeba Lour and the rhizomes of ginger (Zingiber officinale). Geranial inhibits LPS-induced phosphorylation of ERK1/2, JNK1/3 and IκB in macrophages. It suppresses the secretion of IL-1β, TNF-α and IL-6, as well as the expression of pro-IL-1β, iNOS and COX-2. Geranial increases ROS. It can be used in the research of inflammatory diseases.

LY2409881 trihydrochloride is a selective IκB kinase β (IKK2) inhibitor with an IC₅₀ of 30 nM.

DC-SX029 is a potent SNX10 protein-protein interaction (PPI) inhibitor with oral activity with an estimated K_D constant of ~0.935 μM by surface plasmon resonance (SPR). DC-SX029 blocks the SNX10-PIKfyve interaction, thereby decreased the TBK1/c-Rel signaling activation. DC-SX029 does not affect the protein level of SNX10. DC-SX029 has the potential for inflammatory bowel disease (IBD) research.

SU1261 is an IKK inhibitor with K_i values of 10 nM and 680 nM for IKKα and IKKβ, respectively. SU1261 can inhibit non-canonical NF-κB signaling in U2OS osteosarcoma cells.

PROTAC TBK1 degrader-2 is a potent PROTAC degrader of serine/threonine kinase TANK-binding kinase 1 (TBK1) (DC₅₀=15 nM; K_d=4.6 nM) with a maximum efficiency of 96%. PROTAC TBK1 degrader-2 also targets to IkB kinase IKKε (IC₅₀=8.7 nM), with low selectivity over TBK1 (IC₅₀=1.3 nM).

2'-Acetylacteoside (2'-AA) is a natural compound with oral activity and blood-brain barrier permeability. 2'-Acetylacteosideexhibits MAO‑B inhibitory activity (IC₅₀ = 17.71 μM, K_i = 13.81 μM). 2'-Acetylacteoside downregulates the expression of RANK, TRAF6, NF‑κB, NFATc1 and IKKβ, disrupts the RANKL/RANK interaction, blocks downstream signaling pathways, and increases the level of phosphorylated Akt. 2'-Acetylacteoside possesses potent anti-osteoclastogenic, anti-bone resorptive, pro-neurogenic, neuroprotective and antioxidant activities. 2'-Acetylacteoside can be used in the research of osteoporosis, ischemic stroke and Parkinson's disease.