IKK 16

IKK 16 is an orally active IKK inhibitor. IKK 16 shows IC₅₀s of 40 nM, 70 nM, 200 nM, and 50 nM for IKK2, IKK complex, IKK1, and LRRK 2, respectively. IKK 16 is also a pan-PKD inhibitor, inhibiting PKD1, PKD2, and PKD3 with IC₅₀s of 153.9, 115, and 99.7 nM, respectively. IKK 16 is also an ABCB1 inhibitor, interfering with the binding of ABCB1 to its substrates. IKK 16 protects against LPS (HY-D1056)-induced multiple organ dysfunction by reducing the acute inflammatory response induced by endotoxin exposure. IKK 16 can restore renal function and alleviate fibrosis in acute kidney injury. IKK 16 attenuates cardiac dysfunction associated with polymicrobial sepsis in mice with type 2 diabetes mellitus (T2DM) by inhibiting the NF-κB pathway^{[1][2][3][4][5][6][7]}. IC50 & Target:IC50: 40 nM (IKK2), 70 nM (IKK complex), 200 nM (IKK1)^[1]
IC50: 50 nM (LRRK2)^[2] In Vitro:IKK 16 inhibits IκB degradation and inhibits TNFα-stimulated E-Sel, ICAM, VCAM, β2M, and HLA-DR expression in HUVEC cells, with IC₅₀s of 1, 0.5, 0.3, 0.3, 2, 2 μM, respectively^[3].
IKK 16 (20 μM) inhibits phosphorylation of Ser910, Ser935, Ser955 and Ser973 in Flp-In T-REx^™ HEK293 GFP-LRRK2 G2019S cells^[4].
IKK 16 (20 μM) rescues phosphorylation of Ser910, Ser935, Ser955 and Ser973 in Flp-In T-REx™ HEK293 LRRK2 A2016T/G2019S mutant^[4].
IKK 16 (1 μM) inhibits PKD1 activity by 67%,is ATP-competitive inhibitors^[6].
IKK 16 (1-100 μM) inhibits PKCα and PKCδ^[6].
In Vivo:IKK 16 (1 mg/kg, i.v., once) protects against LPS-induced multiple organ dysfunction by reducing the acute inflammatory response induced by endotoxin exposure in male Wistar rats model^[1].
IKK 16 (1 mg/kg, i.v., once) improves recovery of renal glomerular and tubular function, prevents fibrosis at 28 days after the AKI insult in male Wistar rats model^[2].
IKK 16 (30 mg/kg, s.c., once) suppresses systemic TNFα levels in LPS-induced rats model^[3].
IKK 16 (10 mg/kg, s.c., once) inhibits neutrophil extravasation in thioglycollate-induced peritonitis mice model^[3].
IKK 16 reduces CLP-induced cardiac dysfunction, NF-κB pathway activation and iNOS expression in high fat (HFD)-caecal ligation and puncture (CLP) mice model^[5].