RIPK2 Inhibitor

GLPG3312 (Compound 28) is an orally active SIK inhibitor with IC₅₀ values of 2.0 nM, 0.7 nM and 0.6 nM for SIK1, SIK2 and SIK3, respectively. GLPG3312 exhibits anti-inflammatory and immunomodulatory activity in vitro on human primary myeloid cells and in vivo in mouse models. GLPG3312 has good oral bioavailability and can be used for research on inflammatory and immune diseases.

WEHI-345 is a potent and selective RIPK2 kinase inhibitor with an IC₅₀ of 0.13 μM, which delays RIPK2 ubiquitylation and NF-κB activation on oligomerization domain (NOD) stimulation.

GSK2983559 is an orally active and potent receptor interacting protein 2 (RIP2) kinase inhibitor. GSK2983559 blocks many proinflammatory cytokine responses in vivo and in human inflammatory bowel disease explant samples.

RIPK-IN-4 is a selective RIPK2 inhibitor with an IC₅₀ value of 3 nM. RIPK-IN-4 can be used for the research of inflammatory diseases.

PROTAC RIPK degrader-6 (Example 1) is a RIPK2 PROTAC degrader that recruits cereblon. PROTAC RIPK degrader-6 recruits the CRBN E3 ubiquitin ligase complex and induces the degradation of RIPK2 kinase via the ubiquitin-proteasome pathway, thereby blocking NOD1/NOD2-mediated pro-inflammatory signaling pathways of NF-κB and MAPK. PROTAC RIPK degrader-6 can be used in research related to RIPK2-mediated autoinflammatory diseases and cancer.

LT-1339-553 is a selective, orally active RIPK1 inhibitor with IC₅₀ values of 4.32, 95.74 and 84.33 nM against RIPK1, RIPK2 and RIPK3, respectively. LT-1339-553 exerts anti-necroptotic activity by inhibiting the AKT/PI3K/NF-κB pathway and the IL-17 pathway. LT-1339-553 reduces liver injury, inflammatory responses and collagen deposition. LT-1339-553 can be used in studies related to schistosomiasis-induced liver fibrosis.

GSK2983559 active metabolite is an active metabolite of GSK2983559. GSK2983559 active metabolite is a receptor interacting protein-2 (RIP2) kinase inhibitor extracted from patent WO/2014043446 A1, compound example 1.

OD36 is a RIPK2 inhibitor with an IC₅₀ of 5.3 nM. OD36 is a macrocyclic inhibitor with potent binding to the ALK2 kinase ATP pocket. OD36 shows ALK2-directed activity with K_Ds of 37 nM.

GSK2983559 free acid (compound 3) is an orally active and potent receptor interacting protein 2 (RIP2) kinase inhibitor. GSK2983559 free acid can block many proinflammatory cytokine responses in vivo and in human inflammatory bowel disease explant samples.

HTH-01-091 is a potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor, with an IC₅₀ of 10.5 nM. HTH-01-091 also inhibits PIM1/2/3, RIPK2, DYRK3, smMLCK and CLK2. HTH-01-091 can be uesd for breast cancer research.

WEHI-345 analog is the analog of WEHI-345. WEHI-345 is a potent and selective RIPK2 kinase inhibitor with an IC₅₀ of 0.13 μM, which delays RIPK2 ubiquitylation and NF-κB activation on oligomerization domain (NOD) stimulation.

OD36hydrochloride is a RIPK2 inhibitor with an IC₅₀ of 5.3 nM. OD36 hydrochloride is a macrocyclic inhibitor with potent binding to the ALK2 kinase ATP pocket. OD36 hydrochloride shows ALK2-directed activity with K_Ds of 37 nM.

RIPK2/3-IN-2 (29) is a dual RIPK2 and RIPK3 inhibitor, with IC₅₀ values of 12 nM and 18 nM, respectively. RIPK2/3-IN-2 (29) induces necroptosis, with an EC₅₀ of 0.16 μM.

NOD1-RIPK2-IN-1 (Compound 37) is a NOD1-RIPK2 signaling pathway inhibitor with IC₅₀ values of 42 nM and 1.52 nM for NOD1 and RIPK2, respectively. NOD1-RIPK2-IN-1 reduces the secretion of the pro-inflammatory cytokine IL-8 and can be used in the research of inflammation and immune-related diseases.

RIPK2-IN-8 is an orally active and highly selective RIPK2 inhibitor (IC₅₀ = 11 nM). RIPK2-IN-8 is highly selective for RIPK2 over RIPK1 (IC₅₀ > 30,000 nM) and has a moderate inhibitory effect on RIPK3 (IC₅₀ = 44.61 nM). RIPK2-IN-8 inhibits the NOD2-RIPK2 signaling pathway and the expression of the inflammatory cytokines IL-6 and TNFα, thereby exerting anti-inflammatory effects. RIPK2-IN-8 has demonstrated anti-inflammatory and hepatoprotective effects in an acute liver injury (ALI) model and can be used in ALI research.

CSLP43 is a selective RIPK2 and XIAP inhibitor with an IC₅₀ of 19.9 nM against human RIPK2. CSLP43 binds to the ATP-binding pocket of RIPK2 and disrupts the interaction between RIPK2 and the BIR2 domain of XIAP or cIAP1. CSLP43 inhibits RIPK2 ubiquitination, NOD1-dependent inflammatory signaling pathways, NOD2-dependent inflammatory signaling pathways, as well as NF-κB activation associated with NOD agonists. CSLP43 is selective for the NOD1/NOD2 signaling pathway and does not inhibit the kinase activity of RIPK1 or RIPK3. CSLP43 is applicable to research related to Crohn's disease, Blau syndrome, early-onset sarcoidosis and early-onset inflammatory bowel disease.

RIPK2-IN-2 (example 25) is a RIP2 kinase PROTAC inhibitor. RIPK2-IN-2 can block RIP2-dependent proinflammatory signaling, regulated RIP2 kinase activity in auto inflammatory diseases.

RIPK2-IN-7 (Compound 10w) is an orally active, selective RIPK2 inhibitor (IC₅₀: 0.6 nM). RIPK2-IN-7 inhibits RIPK2 kinase activity, blocks the nucleotide-binding oligomerization domain (NOD) signaling pathway, and reduces the production of inflammatory factors (such as TNFα). RIPK2-IN-7 can be used in the study of inflammatory bowel disease (IBD).

RIP2 Kinase Inhibitor 4 is a potent and selective RIPK2 PROTAC. RIP2 Kinase Inhibitor 4 effectively degrades RIPK2 (pIC₅₀ of 8) and inhibits the release of related TNF-α.

CSLP37 is a selective RIPK2 inhibitor with an IC₅₀ of 16.3 nM. CSLP37 shows no inhibitory activity against RIPK1 and RIPK3. CSLP37 displays potent suppression of cellular NOD1 and NOD2 responses.