tak1 inhibitor

TAK1 inhibitor is an inhibitor, which can inhibit MCF-7, A549, DU-145 and MDA MB-231, with IC50 of 0.021, 0.14, 0.064 and 0.19, respectively. TAK1 inhibitor showed good antibacterial activity with microphones ranging from 93.7 to 46.9μg mL and from 7.8 to 5.8μg mL.

TAK1 MAP4K2 inhibitor 1 (compound 5) is a dual kinase inhibitor of TAK1 and MAP4K2 with IC50 values of 41.1 nM and 18.2 nM, respectively.

Takinib (EDHS-206) is a specific and effective TAK1 inhibitor(IC50= 9.5 nM).

NG25 is a potent dual inhibitor of TAK1 and MAP4K2, with IC50s of 149 nM and 21.7 nM, respectively.

TAK-715 is a p38 MAPK inhibitor for p38α.

HM43239 is an orally active and selective FLT3 inhibitor with IC 50 s of 1.1 nM, 1.8 nM and 1.0 nM for FLT3 WT, FLT3 internal tandem duplication (ITD) and FLT3 D835Y kinases, respectively. HM43239 directly inhibits the kinase activity of FLT3 as a reversible Type I inhibitor and effectively modulates downstream p-STAT5 and p-ERK. HM43239 also demonstrated inhibition of SYK, JAK1 2 and TAK1. HM43239 inhibits the proliferation and induces the apoptosis of leukemic cells [1] [2] [3].

5Z-7-Oxozeaenol (FR148083) is a potent, irreversible and selective inhibitor of transforming growth factor (TGF)-β-activated kinase 1 with IC50 of 8.1 nM for TAK1 and low activity against MEK1 with IC50 of 411 nM, it is also an inhibitor of VEGF-R2 with IC50 of 52 nM.

Pelubiprofen is an orally active, non-steroidal anti-inflammatory agent, a selective cyclooxygenase-2 (COX-2) inhibitor, which effectively reduces PGE(2) production by inhibiting COX activity. Pelubiprofen inhibits LPS-induced phosphorylation of IKK-β and transforming growth factor-β activated kinase-1 (TAK1).

TAK-756 is a TAK1 inhibitor that selectively targets IRAK1 4 and exhibits excellent intra-articular pharmacokinetic properties. TAK1 is a potential molecular target for osteoarthritis (OA) due to its complementary anti-catabolic and anti-inflammatory effects.

BPD is a COX-2 and TAK1-NF-κB inhibitor with an IC50 of 18.5 μM for COX-2. It suppresses the expression of iNOS, TNF-α, IL-6, and IL-1β at the transcriptional level. BPD possesses anti-inflammatory properties and can inhibit carrageenan-induced paw edema as well as LPS-induced septic death.

RGB-286638 free base is a novel CDK inhibitor with IC50s of 1 nM 2 nM 3 nM 4 nM 5 nM for cyclin T1-CDK9 cyclin B1-CDK1 cyclin E-CDK2 cyclin D1-CDK4 cyclin E-CDK3 p35-CDK5 respectively; less potent against cyclin H-CDK7 and cyclin D3-CDK6.

PF-05381941 is a selective and potent dual inhibitor of TAK1 and p38α with IC 50 =156 nM 186nM that inhibits the kinase activity of TAK1 by binding to its active site.

SM1-71 is a potent multi-targeted acrylamide-modified TAK1 inhibitor that inhibits MKNK2, MAP2K1 2 3 4 6 7, GAK, AAK1, BMP2K, MAP3K7, MAPKAPK5, GSK3A B, MAPK1 3, SRC, YES1, FGFR1, ZAK (MLTK), MAP3K1, LIMK1 and RSK2.SM1-71 can be used as a kinase probe with anticancer activity and inhibits the proliferation of various cancer cell lines.

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

TAK1-IN-2 is a potent and selective TAK1 inhibitor with an IC50 of greater than 2 nM [1].

TAK1-IN-3 is a novel ATP-competitive TAK1 inhibitor for the study of cancer.

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.

INH14 is a novel inhibitor of the IKKα β-dependent TLR inflammatory response (IC50s: 8.97 3.59 μM for IKKα IKKβ).

HS220 is an inhibitor of TAK1 which plays a key role in the signaling pathways of inflammation and cell survival.

HS-243 is an inhibitor of IRAK-4 and IRAK-1 with IC50s of 20 and 24 nM. HS-243 shows anti-inflammatory and anticancer activity.

(R)-STU104 is a novel TAK1-MKK3 protein-protein interaction (PPI) inhibitor that inhibits TNF-α and suppresses the TAK1 MKK3 p38 MnK1 MK2 elF4E signalling pathway by binding to MKK3 and disrupting TAK1 phosphorylation of MKK3. (R)-STU104 is a candidate compound for the treatment of ulcerative colitis.

HS-276 is a highly selective, orally active inhibitor of TAK1 (Ki: 2.5 nM). HS-276 significantly inhibits TAK1 (IC50: 8.25 nM), CLK2 (IC50: 29 nM), GCK (IC50: 22 nM), ULK2 (IC50: 63 nM), MAP4K5 (IC50. HS-276 can be used to study rheumatoid arthritis (RA).

IRAK4-IN-21 is a selective, orally active, potent IRAK4 inhibitor that acts on IRAK4 (IC50: 5 nM) and TAK1 (IC50: 56 nM). IRAK4-IN-21 exhibits potent inhibition of IL-23 production with an IC50 value of 0.17 μM. can be used to study autoimmune diseases, such as plaque psoriasis and psoriatic arthritis.

IRAK4-IN-22 is a selective, orally active, potent IRAK4 inhibitor that acts on IRAK4 (IC50: 3 nM) and TAK1 (IC50: 17 nM). IRAK4-IN-21 exhibits potent inhibition of IL-23 production with an IC50 value of 0.10 μM. IRAK4-IN-21 can be used to study autoimmune diseases, such as plaque psoriasis and psoriatic arthritis.