TBK1 Inhibitor

BX795 is a potent and selective inhibitor of PDK1, with an IC₅₀ of 6 nM. BX795 is also a potent and relatively specific inhibitor of TBK1 and IKKε, with an IC₅₀ of 6 and 41 nM, respectively. BX795 blocks phosphorylation of S6K1, Akt, PKCδ, and GSK3β, and has lower selectivity over PKA, PKC, c-Kit, GSK3β etc. BX795 modulates autophagy.

GSK8612 is a highly selective and potent Tank-binding Kinase-1 (TBK1) inhibitor, with a pIC₅₀ of 6.8 for recombinant TBK1.

Amlexanox (AA673; Amoxanox; CHX3673) is a specific inhibitor of IKKε and TBK1, and inhibits the IKKε and TBK1 activity determined by MBP phosphorylation with an IC₅₀ of approximately 1-2 μM.

MRT67307 is a dual inhibitor of the IKKε and TBK-1 with IC₅₀s of 160 and 19 nM, respectively. MRT67307 also inhibits ULK1 and ULK2 with IC₅₀s of 45 and 38 nM, respectively. MRT67307 also blocks autophagy in cells.

BAY-985, a chemical probe, is a highly potent, orally active and selective ATP-competitive dual inhibitor of TBK1 and IKKε with IC₅₀s of 2/30 and 2 nM for TBK1 (low/high ATP) and IKKε, respectively. Antitumor efficacy.

STING-IN-19 is a STING inhibitor with a K_d value of 2.31 μM for human STING. STING-IN-19 inhibits the activation of TBK1 and IRF3 by binding to STING, thereby suppressing the activation of downstream signaling pathways. STING-IN-19 reduces the levels of key inflammatory cytokines IL-1β, IL-6 and TNF-α in colonic tissues and serum of mice with ulcerative colitis. STING-IN-19 can be used in studies related to ulcerative colitis.

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.

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

STING-IN-7 is a potent STING inhibitor with an IC₅₀ of 11.5 nM. STING-IN-7 can inhibit the phosphorylation of STING, IRF3, and TBK1. STING-IN-7 can be used in the research of autoimmune and inflammatory diseases.

TBK1/IKKε-IN-4 is a 6-aminopyrazolopyrimidine derivative and a potent, selective TBK1 and IKKε inhibitor with IC₅₀ values of 13 nM and 59 nM, respectively. TBK1/IKKε-IN-4 shows 100- to 1000-fold less activity against other protein kinases including PDK1, PI3K family members and mTOR.

GSK319347A is a dual inhibitor of TBK1 and IKKε with IC₅₀s of 93 nM and 469 nM, respectively. GSK319347A also inhibits IKK2 with an IC₅₀ of 790 nM.

PROTAC STING degrader-4 is a nitro-free covalent STING PROTAC degrader with a DC₅₀ of 3.23 μM. PROTAC STING degrader-4 effectively inhibits STING as well as its downstream signaling, such as p-TBK1 and p-NF-κB (p-P65), and immune-inflammatory cytokines. PROTAC STING degrader-4 mitigates kidney and blood inflammation in Cisplatin (HY-17394)-induced acute kidney injury (AKI) mice model.

MRT67307 hydrochloride is a dual inhibitor of the IKKε and TBK-1 with IC₅₀s of 160 and 19 nM, respectively. MRT67307 hydrochloride also inhibits ULK1 and ULK2 with IC₅₀s of 45 and 38 nM, respectively. MRT67307 hydrochloride also blocks autophagy in cells.

TBK1-IN-2 (Compound A1) is a potent TBK1 inhibitor (IC₅₀: 775 pM). TBK1-IN-2 binds to TBK1 through stable hydrogen bonds and π-π stacking, inhibiting IRF3 phosphorylation. TBK1-IN-2 synergizes with TNF/IFNγ to enhance immune-mediated tumor cell death. TBK1-IN-2 can be used in cancer immunotherapy research.

SMU-14a is a selective Toll-like receptor 3 (TLR3) inhibitor wirh an IC₅₀ of 0.18 μM. SMU-14a reduces phosphorylation of p65, ERK, and TBK1 via NF-κB, MAPK, and IRF3 signaling pathways. SMU-14a inhibits IL-6 secretion in mouse peritoneal macrophages, downregulates TNF-α in human peripheral blood monocytes and decreases serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. SMU-14a can be used for the research of acute hepatitis.

(Rac)-BAY-985 (Compound Example 100.01) is a potent, ATP-competitive and selective TBK1 inhibitor with an IC₅₀ of 1.5 nM. Antitumor efficacy.

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.

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.

UM-203 is a reversible covalent STING antagonist. UM-203 is effective against both mouse and human STING, and in particular, it inhibits the most common human STING R232 variant. UM-203 can inhibit STING oligomerization and reduce phosphorylation of downstream TBK1 and IRF3, thereby blocking the IRF3 and NF-κB-mediated signaling pathways and inhibiting IFNβ and IL-6 secretion. UM-203 can be used for the research of inflammation and immunology, such as systemic lupus erythematosus.

ITA-5 is a TBK1 inhibitor based on the structure of itaconic acid. can significantly inhibit the secretion of IFN-β. ITA-5 can inhibit the phosphorylation of TBK1, IRF3, and STAT1. ITA-5 can be used for research on autoimmune diseases and excessive inflammation.