ripkinase

Necrostatin-1 (Nec-1) is a specific RIP1 inhibitor and necrotic apoptosis inhibitor, which inhibits TNF-α-induced necrotic apoptosis and also inhibits IDO.

RIPK1-IN-7 is a potent and selective inhibitor of RIPK1 (Kd of 4 nM and enzymatic IC50 of 11 nM), exhibiting excellent antimetastasis activity in the experimental B16 melanoma lung metastasis model.

RIP1 Kinase Inhibitor 4 (Compound 3) is an effective inhibitor of RIP1K, exhibiting an EC50 of ≤ 1000 nM [1].

RIP1 Kinase Inhibitor 7 (Compound 41) serves as a potent inhibitory agent for receptor interacting protein 1 kinase (RIP1) with an IC50 of under 100 nM. Additionally, it demonstrates an EC50 ranging from 1 to 100 nM in cell necrosis assays [1].

PK68 is an effective and selective inhibitor of type II receptor-interacting kinase 1 (RIPK1, IC50 = 90 nM). PK68 can be used for research on the treatment of inflammatory disorders and cancer metastasis.

RIPK1-IN-16 is an orally active, potent RIPK1 inhibitor that mitigates excessive inflammation via inhibition of RIPK1-mediated necroptosis in vivo, protecting mice from TNF-induced systemic inflammatory response syndrome and sepsis [1].

RIP1 Kinase Inhibitor 6 is a potent and selective inhibitor of RIP1 kinase, demonstrating inhibitory activity with an IC50 of less than 100 nM in a human R1P1 kinase assay[1].

RIPK3-IN-4 (Compound 42) is a RIPK3 inhibitor that mitigates necroptosis, inflammatory responses, and HK-2 cell damage. It alleviates acute kidney injury by attenuating Cisplatin- and I R-induced kidney damage, along with associated inflammatory responses and necroptosis [1].

OD36 hydrochloride (OD-36 hydrochloride) is a potent RIPK2 inhibitor with an IC50 of 5.3 nM.OD36 hydrochloride is a macrocyclic inhibitor that binds efficiently to the ATP pocket of the ALK2 kinase and effectively antagonizes mutant ALK2 signaling and osteogenic differentiation.OD36 hydrochloride targets ALK2. OD36 hydrochloride targets ALK2 with a KD of 37 nM.

RIPK1-IN-17 is a dual inhibitor of RIPK1 and RIPK3 that specifically inhibits necrosis by inhibiting phosphorylation of RIPK1, RIPK3 and MLKL, protecting mice from hypothermia and death in a tnf-induced inflammation model.

RIP1 kinase inhibitor 5 (example 1) is a potent regulator of tumor immunity, inhibiting RIP1 and similarly to SIR1-365 (compound 13), suppresses necrosis and ferroptosis [2].

RIPK2 3-IN-1 is a potent inhibitor of both RIPK2 and RIPK3 kinases, exhibiting IC50 values of 3 nM for RIPK2 and 117 nM for RIPK3. Additionally, in a 14-TriLAN-Gly NOD1 THP-1 cell-based NF-κB reporter assay, RIPK2 3-IN-1 demonstrates an IC50 value of 14 ± 4 nM against RIPK2 [1].

SZM679 is an orally active, selective RIPK1 inhibitor displaying potent affinity with a dissociation constant (Kd) of 8.6 nM for RIPK1, while exhibiting minimal activity towards RIPK3, with a Kd of >5000 nM. It effectively counteracts tumor necrosis factor-induced systemic inflammation, reduces Tau hyperphosphorylation, diminishes neuroinflammation, and lowers RIPK1 phosphorylation in the hippocampus and cortex. SZM679 is utilized in Alzheimer's disease (AD) research [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].

RIPK1-IN-9 is a potent and selective inhibitor of RIPK1, a dihydronaphthone compound, which inhibits U937 and L929 cells with an IC50 of 2 nM and 1.3 nM, respectively.

LD4172 is a PROTAC degrader capable of degrading RIP kinase (RIPK1) with a DC50 in the nanomolar range. When used in combination with TNF-α, LD4172 can induce apoptosis in B16F10 cells. In mouse models, it demonstrates antitumor activity. (Pink: ligand for target protein; Black: linker; Blue: ligand for E3 ligase VHL)

RIPK1-IN-28 (compound 13) is an orally active inhibitor of RIPK1. It exhibits inhibitory effects on human I2.1 and Hepa1-6 cells, with IC50 values of 0.4 and 1.2 nM, respectively.

Ocadusertib is an effective inhibitor of the serine threonine kinase receptor-interacting protein kinase 1 (RIPK1).

ZB-R-55 is an orally available and highly potent bimodal RIPK1 inhibitor with excellent kinase selectivity in lps-induced sepsis models for the study of SIRS and sepsis.

RIPK1-IN-19 is a selective and potent bimodal RIPK1 inhibitor with IC50=15 nM that protects against cell necrosis and works well in the tnf α-induced Systemic Inflammatory Response Syndrome (SIRS) model and imiquimod (IMQ)-induced psoriasis model.

RI-962 is a potent and selective inhibitor of RIPK1 that dose-dependently protects cells from necrotic apoptosis induced by TNFα, Smac mimics, and Z-VAD-FMK by inhibiting RIPK1, RIPK3, and MLKL phosphorylation with EC50=10.0 nM~17.8 nM, and improves survival in mice in two models of inflammation.

CSLP37 is a selective RIPK2 inhibitor with an IC50 of 16.3 nM and demonstrates no inhibitory activity against RIPK1 or RIPK3. Additionally, CSLP37 effectively suppresses cellular responses mediated by NOD1 and NOD2.

TopoisomeraseI II inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of TopoisomeraseI II that induces DNA damage and activates PARP-1, leading to the activation of RIPK1, RIPK3, and MLKL, ultimately causing necroptosis. It shows significant anticancer activity by effectively targeting cancer cell nuclei and inducing cell death through necroptosis, offering substantial clinical potential in overcoming resistance in cancer treatment.

Anticanceragent 267 (Compound 5q) serves as an activator of RIPK3 and MLKL. It effectively inhibits the proliferation of several cancer cell lines, with IC50 values of 9.79, 10.77, and 5.94 μM for MDA-MB-231, MDA-MB-486, and MCF-7, respectively. The compound induces cell cycle arrest at the subG1 phase and triggers necroptosis in MDA-MB-231 cells. Additionally, Anticanceragent 267 demonstrates antitumor activity in mouse xenograft models.