IKK Inhibitor

IKKβ-IN-3 (Compound hit4) is a IKKβ inhibitor with an IC₅₀ value of 30.4 nM. IKKβ is a key enzyme in the NF-κB signaling pathway and is involved in the development of many diseases. IKKβ-IN-3 can be used in the study of CAF-induced arthritis.

OSU-53 is an orally active AMPK activator and mTOR inhibitor, with an IC₅₀ of 0.3 μM for AMPK, an EC₅₀ of 2-5 μM for AMPK, and an IC₅₀ of 8.23 μM for mTOR. OSU-53 inhibits the Akt signaling pathway, directly activates AMPK by binding to its autoinhibitory domain, reduces IKKβ-mediated phosphorylation of Foxo3a, blocks Akt-mediated phosphorylation of MDM2, and promotes the nuclear localization and stabilization of Foxo3a, while directly inhibiting mTOR. OSU-53 inhibits epithelial-mesenchymal transition (EMT), induces epithelial phenotype, suppresses invasion and metastasis, induces autophagy, inhibits the activation of ERK and Akt, reduces the secretion of nitric oxide and proinflammatory cytokines, and inhibits the migration of MDSC; at high doses, it induces MDSC apoptosis, attenuates the immunosuppressive effect of MDSC, reduces MDSC levels, and blocks incision-induced mechanical hyperalgesia. OSU-53 can be used in studies related to breast cancer, prostate cancer, thyroid cancer, melanoma and postoperative pain.

SR8185 is a potent and selective TBK1/IKKi dual inhibitor with IC₅₀s of 3 nM and < 10 nM against IKKi and TBK1, respectively. SR8185 exhibits potent and broad spectrum antiproliferative effects on human cancer cells. SR8185 can be used for cancer research.

IKKβ-IN-7 is an IKKβ inhibitor with an IC₅₀ value of 9.44 μM. IKKβ-IN-7 induces DNA damage, S-phase cell cycle arrest, ROS accumulation, mitochondrial membrane potential loss, and apoptosis. IKKβ-IN-7 inhibits phosphorylation of p65 and IκBα, suppresses p65 nuclear translocation, and regulates NF-κB-controlled genes. IKKβ-IN-7 suppresses tumor growth in xenograft models and shows activity against colorectal cancer with low normal cell cytotoxicity. IKKβ-IN-7 can be used for the research of colorectal cancer.

Nandinine is an orally active derivative of Berberine (HY-N0716). Nandinine enhances AMPK activity, inhibits the activation of IKKβ/NF-κB, and regulates the phosphorylation of IRS-1. Nandinine reverses the abnormal production of adipokines, promotes insulin-mediated glucose uptake, and alleviates insulin resistance. Nandinine improves glucose tolerance and increases the insulin sensitivity index in mice. Nandinine can be used in studies related to insulin resistance.

CS12192 is a compound improving survival and weight gain. CS12192 has the potential for the research of graft-versus-host disease (GVHD) (extracted from the patent CN112773802A).

Acutissimalignan B is a natural product. Acutissimalignan B can be isolated from Daphne kiusiana var. atrocaulis (Rehd.) F. Maekawa. Acutissimalignan B can reduce the mRNA expression of inflammatory cytokines (iNOS, TNF-α, IL-1β, and IL-6), inhibit the phosphorylation of IκBα, and inhibit the nuclear translocation of NK-κB p65. Acutissimalignan B shows anti-neuroinflammatory effects.

Albaconol is a prenylresorcinol compound. Albaconol is isolated from the mushroom A. confluens. Albaconol inhibits NF-κB and DNA topoisomerase II, and induces Apoptosis. Albaconol inhibits IκB-α phosphorylation and p65 nuclear translocation, enhances SOCS1 expression, reduces the production of proinflammatory cytokines and NO, and suppresses the expression of iNOS, MHC-II and co-stimulatory molecules. Albaconol acts as a weak antagonist of hVR1 and rVR1, with IC₅₀ values of 17 µM and 5.5 µM, respectively. Albaconol induces tracheal contraction and desensitization. Albaconol inhibits the growth of tumor cells. Albaconol can be used in pain-related research.

EC-70124 is an orally active multikinase inhibitor targeting IKKβ and JAK2. EC-70124 blocks IkB phosphorylation and STAT3 (Tyr705) activation, suppressing NF-κB nuclear translocation and STAT3 transcriptional activity. EC-70124 reduces tumor growth and cancer stem cell (CSC) populations in prostate cancer cells and xenograft models. EC-70124 is promising for research of prostate cancer.

IKKβ-IN-1 is a potent and orally active IkappaB (IKK-β) inhibitor with IC₅₀ of 0.20 μM. IKKβ-IN-1 can reduce PGE₂ and TNF-α production in mouse macrophage cells. IKKβ-IN-1 has the ability to protect mice against septic shock induced mortality.

TBK1/IKKε-IN-6 (example 110) is a TBK1 and IKKε inhibitor, with IC₅₀ values of <100 nM for both TBK1 and IKKε.

(Rac)-Mefloquine ((Rac)-Mefloquin) is an orally active NF-κB inhibitor. (Rac)-Mefloquine inhibits the NF-κB and IKK signaling pathways, suppresses NF-κB-Luc luciferase activity, blocks the activation of p65 and IκBα, and reduces the expression of downstream target genes of NF-κB. (Rac)-Mefloquine activates apoptosis-related factors and induces apoptosis in tumor cells. (Rac)-Mefloquine functions as a tumor cell inhibitor. (Rac)-Mefloquine can be used for the research of colorectal cancer.

(9S,13R)-12-Oxo phytodienoic acid-d₅ ((9S,13R)-12-OPDA-d₅) is the deuterated-labeled (9S,13R)-12-Oxo phytodienoic acid (HY-118828A). (9S,13R)-12-Oxo phytodienoic acid ((9S,13R)-12-OPDA) is a mPGES-1 inhibitor and Nrf2 activator. (9S,13R)-12-Oxo phytodienoic acid selectively inhibits mPGES-1 expression and reduces inducible PGE₂ production without affecting COX-1 or COX-2. (9S,13R)-12-Oxo phytodienoic acid inhibits the phosphorylation of IKKβ, IκBα, and NF-κB (p65), blocks the nuclear translocation of p65, increases the nuclear translocation of Nrf2, and upregulates HO-1 expression. (9S,13R)-12-Oxo phytodienoic acid inhibits the differentiation of M0 macrophages toward the M1 phenotype and promotes differentiation toward the M2 phenotype. (9S,13R)-12-Oxo phytodienoic acid decreases the levels of NO, PGE₂, IL-1β, IL-6, iNOS, and PGD₂. (9S,13R)-12-Oxo phytodienoic acid can be used for inflammation research.

MRT 68601 hydrochloride is a TBK1 inhibitor with an IC₅₀ value of 6 nM. MRT 68601 hydrochloride inhibits autophagosome formation in lung cancer cells.

Resveratrol-¹³C₆ is the ¹³C-labeled Resveratrol. Resveratrol (trans-Resveratrol; SRT501), a natural polyphenolic phytoalexin that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. Resveratrol (SRT 501) has a wide spectrum of targets including mTOR, JAK, β-amyloid, Adenylyl cyclase, IKKβ, DNA polymerase. Resveratrol also is a specific SIRT1 activator. Resveratrol is a potent pregnane X receptor (PXR) inhibitor. Resveratrol is an Nrf2 activator, ameliorates aging-related progressive renal injury in mice model. Resveratrol increases production of NO in endothelial cells.

STING-IN-17 (compound 10a) is an orally active STING (human STING IC₅₀ = 29 nM, mouse STING IC₅₀ = 15 nM) inhibitor. STING-IN-17 can inhibit the phosphorylation of STING, TBK1 and IRF3. STING-IN-17 dose dependently inhibits the mRNA expression of IP10, IFNB1 and ISG56. STING-IN-17 can reduce ROS and inhibit the expression of cleaved-PARP/caspase-3. STING-IN-17 can improve kidney function. STING-IN-17 can be used for research on inflammatory conditions such as acute kidney injury.

NDM-622 is a Colistin (HY-113678) adjuvant. NDM-622 weakly inhibits IKKβ with an IC₅₀ of 20.40 μM. NDM-622 reduces the minimum inhibitory concentration of colistin against colistin-highly-resistant Acinetobacter baumannii and Klebsiella pneumoniae. NDM-622 decreases bacterial colony-forming units in a mouse peritonitis model infected with colistin-highly-resistant Klebsiella pneumoniae. NDM-622 does not modify bacterial lipid A, induce reactive oxygen species production, or increase bacterial membrane permeability. NDM-622 can be used in the research of extensively drug-resistant Gram-negative bacterial infections, colistin-resistant Acinetobacter baumannii infections, and Klebsiella pneumoniae infections.

Oxaprozin potassium 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 potassium also inhibits the activation of NF-κB. Oxaprozin potassium induces cell apoptosis. Oxaprozin potassium shows anti-inflammatory activity. Oxaprozin potassium-mediated inhibition of the Akt/IKK/NF-κB pathway contributes to its anti-inflammatory properties.

(E/Z)-HOIPIN-1 ((E/Z)-JTP-0819958) is a selective linear ubiquitin chain assembly complex (LUBAC) inhibitor with an IC50 value >2.8 μM. HOIPIN-1 inhibits LUBAC-mediated NF-kB activation.

NF-κB-IN-21 is a NF-κB signaling pathway inhibitor. NF-κB-IN-21 reduces the phosphorylation levels of IκBα and p65, and inhibits the nuclear translocation of p65. NF-κB-IN-21 downregulates the expression of iNOS, inhibits nitric oxide production, and decreases the levels of pro-inflammatory cytokines TNF-α and IL-6. NF-κB-IN-21 is used in the research of inflammatory diseases.