ripk1 in 3

RIPK1-IN-3 is a RIPK1 inhibitor, with anti-inflammatory proprieties.

RIPK1-IN-30 (compound 24) is a potent RIPK1 inhibitor with an IC50 of 2.01 μM. It demonstrates a protective effect in the HT-29 cell model of TSZ-induced necroptosis, with an EC50 of 6.77 μM.

RIPK1-IN-31 (Compound 36) is a selective allosteric modulator of RIPK1 (Receptor Interacting Protein Kinase 1) with an IC50 value of 16 nM. It holds potential for research in areas such as infections, autoimmune disorders, and neurodegenerative diseases.

RIPK1-IN-32 is an RIPK inhibitor with anti-inflammatory properties. It inhibits nitric oxide (NO) release, with an IC50 of 3.26 μM. Additionally, RIPK1-IN-32 disrupts the RIPK1/NF-κB/MAPK signaling pathway, preventing nuclear translocation of p65 and c-fos, leading to reduced expression of TNF-α and IL-6 and significantly alleviating acute liver injury related to sepsis. This compound is useful for studies on acute liver injury and sepsis.

RIPK1-IN-33 is an orally active RIPK1 inhibitor with excellent blood-brain barrier permeability, exhibiting an IC50 of 0.115 μM. It demonstrates significant anti-ferroptosis activity, radical scavenging capability (IC50= 123.3 μM), and anti-lipid peroxidation effects (IC50= 9.72 μM). In transient middle cerebral artery occlusion (tMCAO) models, it significantly reduces cerebral infarct volume and improves neurological scores. RIPK1-IN-33 is suitable for ischemic stroke research.

RIPK1-IN-34 is a selective RIPK1 inhibitor capable of penetrating the blood-brain barrier with an IC50 of 126.70 nM, showing minimal inhibition of RIPK3 (IC50 > 10,000 nM). It exerts significant neuroprotective effects by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) in the necroptosis pathway. RIPK1-IN-34 demonstrates neuroprotective effects in rat models of middle cerebral artery occlusion (MCAO) and is a candidate for research in the treatment of acute ischemic stroke (AIS).

RIPK1-IN-38 is an orally active inhibitor of RIPK1 with an IC50 of 27 nM. It effectively suppresses the phosphorylation of RIPK1 and its downstream targets RIPK3 and MLKL. Demonstrating anti-necroptosis activity, RIPK1-IN-38 exhibits excellent anti-inflammatory properties in SIRS and GVHD models, making it suitable for research into inflammation and immune-related diseases.

RIPK1-IN-39 (compound 2) is a potent and selective inhibitor of RIPK1 with an IC50 of 69.40 nM, exhibiting over 100-fold selectivity for RIPK1 over RIPK3 (IC50= 6946 nM). It protects HT-22 and HT-29 cells from necroptosis by inhibiting the phosphorylation and activation of the RIPK1-RIPK3-MLKL pathway. Additionally, RIPK1-IN-39 shows neuroprotective effects in a rat middle cerebral artery occlusion (MCAO) model. This compound is applicable in acute ischemic stroke (AIS) research.

Necrostatin-34 (2-{[3-cyano-4-(4-methylphenyl)-6-oxo-1,4) is a RIPK1 kinase inhibitor, stabilizing RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain.