ripk1

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.

RIPK1-IN-4 is a potent and selective type II kinase receptor interacting protein 1 (RIP1) kinase inhibitor and binds to a DLG-out inactive form of RIP1 (IC50s of 16 nM and 10 nM for RIP1 and ADP-Glo kinase).

RIPK1/3-IN-1 (Compound 10) is a selective inhibitor of both RIPK1 and RIPK3, effectively preventing necroptosis by blocking the phosphorylation of RIPK1, RIPK3, and MLKL [1].

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

RIPK1-IN-15 (Compound 2.5) is a potent RIPK1 inhibitor that has the potential in neurodegenerative, autoimmune, and inflammatory diseases research [1].

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

RIPK1-IN-13 (Compound 8) is an effective RIPK1 inhibitor (IC50=1139 nM). By inhibiting RIPK1, RIPK1-IN-13 can block the activation of necrotic apoptosis pathway. RIPK1-IN-13 has research potential in inflammatory diseases.

RIPK1-IN-12 is a potent inhibitor of RIPK1, which exhibits an inhibitory effect on necroptosis in human and mouse cells with EC50 values of 1.6 and 2.9 nM, respectively.

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

RIPK1-IN-8 is an aminoimidazolopyridine and is a selective and potent inhibitor of RIPK1 (IC50: 4 nM).RIPK1-IN-8 has research potential in inflammatory diseases.

RIPK1-IN-11 is an orally active RIPK1 inhibitor with a Kd value of 9.2 nM and an IC50 value of 67 nM. RIPK1-IN-11 inhibits necrosis in human and mouse cells and exhibits anti-inflammatory effects.

RIPK1-IN-10 is a potent inhibitor of RIPK1.

RIPK1-IN-14 (Compound 41) is a potent inhibitor of RIPK1 (IC50: 92 nM).RIPK1-IN-14 has a significant anti-necrotic apoptotic effect in a model of necrotic apoptosis in U937 cells.

Necroptosis-IN-1 is a potent necroptosis inhibitor of RIPK1. It is an analog of Necrostatin-1.

Necrostatin 2 racemate (Necrostatin-2 racemate) is an potent and specific inhibitor of RIPK1.

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.

DB0614 (Example 21) is a bifunctional compound designed for the targeted degradation of kinases, effectively breaking down a wide array of kinases including AAK1, AURKA, BMP2K, CAMKK1, CDK16, CML, CDK6, EIF2AK2, FER, GAK, LCK, LIMK2, MAP3KH, MAPK8, MAPK9, NEK9, PLK4, PTK2B, SIK2, STK17A, STK17B, ULK1, ULK3, and WEE1. This compound has potential applications in the research of diseases or disorders caused by aberrant kinase activity [1].

ICCB-19 hydrochloride (ICCB-19 HCl) is an inhibitor of TRADD (TNFRSF1A Associated Via Death Domain). It binds to a pocket on the N-terminal TRAF2-binding domain of TRADD (TRADD-N), which interacts with the C-terminal domain (TRADD-C) and TRAF2 to modulate the ubiquitination of RIPK1 and beclin 1.

Apostatin-1 (Apt-1) is a novel TRADD inhibitor. Apostatin-1 can bind to a pocket on the N-terminal TRAF2 binding domain of TRADD.

DB1113 (Example 24) is a bifunctional compound designed for the targeted degradation of various kinases. It effectively degrades a range of kinases, including ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1, MAP4K2, MAP4K3, MAP4K5, MAPK14, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1, RPS6KA3, SIK2, SIK3, STK35, TNK2, and ULK1. This capability positions DB1113 as a valuable tool for research into diseases or disorders associated with aberrant kinase activity [1].

KWCN-41, a selective and efficient RIPK1 kinase inhibitor, exhibits an IC50 value of 88 nM. It specifically targets cell necrosis without affecting apoptosis and possesses anti-inflammatory properties [1].

RIPK3-IN-1 is a selective and potent RIPK3 inhibitor (IC50: 9.1 nM) that inhibits the activities of c-Met kinase, RIPK1 and RIPK2.RIPK3-IN-1 has potential tumorigenic activity and can be used to study apoptosis.

Ophiopogonin D(OPD) significantly inhibited the in vitro and in vivo growth of prostate cells via RIPK1, OPD may be developed as a potential anti-prostate cancer agent.

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

TP-030-2 is a RIPK1 inhibitor (human K i =0.43 nM ; mouse IC 50 =100 nM) .

GSK2982772 is an inhibitor of receptor interacting serine/threonine kinase 1 (RIPK1)with IC50 values of 16 nM and 20 nM for human and monkey RIP1, respectively.

Cl-Necrostatin-1 is an inhibitor of receptor-interacting protein kinase. It inhibits RIPK1 activity.

Necrostatin 2 is an effective necroptosis inhibitor. Necrostatin 2 is also a RIPK1 inhibitor. EC50 for inhibition of necroptosis in FADD-deficient Jurkat T cells treated with TNF-α is 0.05 μM.

TP-030-1, an inhibitor of RIPK1, exhibits potent activity against hRIPK1 (human RIPK1) with a Ki value of 3.9 nM and against mRIPK1 (mouse RIPK1) with an IC50 value of 4.2 μM. This compound is instrumental in the research of inflammatory and neurodegenerative diseases.

AV123 (compound 12) is a non-cytotoxic RIPK1 inhibitor with IC 50 of 12.12 μM. AV123 blocks the TNF-α-induced necroptotic with EC 50 of 1.7 μM, but not the 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].

Eclitasertib is a potent inhibitor of receptor-interacting protein kinase 1 (RIPK1, IC50 of <1 µΜ).

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.

RI-962 is a potent and selective inhibitor of receptor-interacting protein kinase 1 (RIPK1), exhibiting an IC50 of 35.0 nM. It is utilized for the investigation of nervous system disorders and inflammatory diseases [1].

GSK3145095 is an orally active inhibitor of RIPK1 with IC50 of 5 nM, with potential immunomodulatory activities and antineoplastic.

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].

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].

Ophiopogonin D is a natural product,and is a CYP2J3 inducer that significantly inhibits Ang II induced NF-κB nuclear translocation.