necroptotic

GW806742X is an inhibitor of Mixed Lineage Kinase Domain-Like protein (MLKL) which binds the MLKL pseudokinase domain (Kd: 9.3 μM) with anti-necroptosis activity. GW806742X has activity against VEGFR2.

RIP3 Activator 1 (compound C8) is an effective RIP3 activator that inhibits cell growth and induces necroptotic cell death (necroptosis) and autophagy through the RIP3/p62/Keap1 signaling pathway. Additionally, this compound enhances the expression of p-MLKL and promotes the accumulation of LC3-II and p62 proteins.

RIPK1-IN-29 (Compound 22) is a RIPK1 inhibitor with an IC50 of 6.9 nM. It exhibits anti-necroptotic apoptosis activity by inhibiting RIPK1. In a TNF-α induced inflammatory in vivo model, a 10 mg/kg dose of RIPK1-IN-29 can protect mice from hypothermia and death. This compound is suitable for research in the field of inflammatory diseases.

RIPK1-IN-23 (compound 19) is an RIPK1 inhibitor with potent anti-necroptotic effects in HT-29 cells (EC50 = 1.7 nM). Additionally, RIPK1-IN-23 exhibits anti-inflammatory properties.

AV123 (compound 12) is a non-cytotoxic RIPK1 inhibitor with an IC50 of 12.12 μM. It blocks TNF-α-induced necroptosis with an EC50 of 1.7 μM, but not apoptotic cell death. AV123 can be used in the study of necrotic chronic conditions such as ischemia-reperfusion injury of the brain, heart, and kidney, inflammatory diseases, neurodegenerative diseases, and infectious diseases [1].

SZM-1209 is a potent and specific RIPK1 inhibitor with oral activity, displaying a dissociation constant (Kd) of 85 nM. It demonstrates substantial anti-necroptotic efficacy with an EC50 of 22.4 ± 8.1 nM and possesses therapeutic effects against systemic inflammatory response syndrome (SIRS) and acute lung injury (ALI) [1].

Necroptosis-IN-5 (Compound 26) is an orally active inhibitor of necroptotic cell death (necroptosis). This compound also exhibits potent inhibitory activity against receptor-interacting protein kinase 1 (RIPK1). It can be utilized in research related to inflammatory diseases, neurodegenerative disorders, and cancer associated with necroptosis.

TC13172-NH-COOH, a PROTAC target protein ligand, is utilized in the synthesis of MLKLPROTAC. This compound is also employed in the investigation of necroptotic-associated diseases.