MLK

GW806742X inhibits MLKL with Kd 9.3 μM, preventing necroptosis; also targets VEGFR2.

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.

PROTAC MLKL Degrader-1 (Compound 36) is a selective PROTAC degrader targeting MLKL, achieving a degradation maximum (D max) over 90%.

MLKL-IN-2 is an MLKL inhibitor with potential tumorigenic activity for the study of cellular necrosis-related diseases.

NecroX-2 is a cell-permeable necrosis inhibitor with antioxidant properties. NecroX-2 selectively suppresses necrotic cell death triggered by oxidative stress. NecroX-2 does not confer protection against apoptosis induced by staurosporine or etoposide but shows protective effects under conditions such as cold shock, hypoxia, and oxidative stress in vitro.

MLKL-IN-7 (compound 9) is an MLKL inhibitor that exhibits anti-necrotic activity in HT-29 cells, with an IC50 value of 148.4 nM.

CEP1347-VHL-02 is a PROTAC that selectively targets MLK3. This compound is composed of the target protein ligand CEP-1347, the E3 ubiquitin ligase ligand (S,R,S)-AHPC-Me, and the PROTAC linker Amino-PEG3-CH2COOH. The participating component responsible for controlling the target protein ligand activity is CEP-1347-acid, whereas the conjugate of the E3 ubiquitin ligase ligand and linker is identified as (S,R,S)-AHPC-Me-CO-CH2-PEG3-NH2.

RIPK3-IN-3 (compound 20) is a selective RIPK3 inhibitor that demonstrates potent activity with an IC50 value of 10 nM.

PROTAC MLKL Degrader-2, a PROTAC that targets MLKL (Mixed Lineage Kinase), incorporates the PROTAC target protein ligand, E3 ligase ligand Thalidomide, and PROTAC Linker N-Methylpiperazine. The conjugate of the E3 ubiquitin ligase ligand and Linker is Thalidomide-N-Methylpiperazine. This compound exhibits antinecroptotic activity in human cell lines and effectively degrades MLKL in the HT-29 xenograft mouse model.

MLK-IN-1 is a potent and selective mixed-lineage kinase 3 (MLK-3) inhibitor, showing excellent brain penetration and high specificity for MLK-3. MLK-IN-1 at 100 nM supports sustained axonogenesis in cultures challenged with HIV-1 Tat-activated microglia and protects neuronal cells from Tat-induced damage, establishing it as a valuable probe for neuroinflammation and neurodegeneration research.

Necrosulfonamide ((E)-Necrosulfonamide) is a necroptosis inhibitor that targets MLKL and is selective. High-Quality, Low-Cost!

MLKL-IN-5 is a potent MLKL inhibitor blocking necroptosis signaling.

SZM-1209 is a potent and specific RIPK1 inhibitor with oral activity, displaying a dissociation constant (Kd) of 85 nM.

IM-54 is a cell-permeable, effective, and selective necrosis inhibitor.

TC13172 is a potent, covalent MLKL inhibitor, selective over RIPK1/RIPK3. It blocks TSZ-induced necroptosis (EC50=2nM) and MLKL oligomerization at 100nM.

MBA-m1 is an MLKL inhibitor that suppresses necroptosis in Mlkl−/−NIH-3T3 cells. Additionally, MBA-m1 alleviates disease conditions in mouse models of dermatitis and abdominal aortic aneurysm induced by MLKL.

MLKL-IN-1 is a covalent inhibitor of MLKL with a Kd value of 50 μM.

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.

MLKL-IN-6 (compound P28) is a mixed lineage kinase inhibitor that specifically targets the Mixed Lineage Kinase domain-like (MLKL) protein.

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).