SZM679 是一种口服有效的选择性RIPK1抑制剂，对 RIPK1 和 RIPK3 的Kd值分别为 8.6 nM 和 >5000 nM。SZM679 逆转肿瘤坏死因子诱导的全身炎症反应。SZM679 可降低海马和皮质中 Tau 蛋白的过度磷酸化、神经炎症和 RIPK1 磷酸化水平。SZM679 可用于阿尔茨海默病 (AD) 的研究。
| 生物活性 | SZM679 is a potent, orally active and selectiveRIPK1inhibitor withKdvalues of 8.6 nM and >5000 nM forRIPK1andRIPK3, respectively. SZM679 reverses the tumor necrosis factor-induced systemic inflammatory response. SZM679 decreases the Tau hyperphosphorylation, neuroinflammation, and theRIPK1phosphorylation level in the hippocampus and cortex. SZM679 can be used in research of Alzheimer's disease (AD)[1]. |
| IC50& Target[1] | RIPK1 8.6 nM (Kd) | RIPK3 >5000 nM (Kd) |
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体外研究
(In Vitro) | SZM679 (0-10 μM; 24 h; necrotic L929 and HT-29 cells) has an anti-necrosis activity by Inhibiting the RIPK1 pathway with an EC50value of 2 nM. SZM679 also protects against TNF-α, cycloheximide, and z-VAD-fmk (TCZ)-induced necroptosis. SZM679 protects against necroptosis induced by TZ in a dose dependent manner[1].
SZM679 (1 μM; 6 h; necrotic HT-29 cells) selectively inhibits the expression of RIPK1 but not RIPK3 or MLKL. SZM679 blocks necrosome formation by inhibiting TSZ-induced phosphorylation of RIPK1[1].
Western Blot Analysis[1] | Cell Line: | Necrotic HT-29 cells | | Concentration: | 1 μM | | Incubation Time: | 6 hours | | Result: | Inhibited the phosphorylation of RIPK1 at 1 μM, resulting in the inhibition of the downstream phosphorylation of RIPK3 and MLKL. |
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体内研究
(In Vivo) | SZM679 (10-40 mg/kg; i.p.; male C57BL/6 J mice with TNF-induced SIRS models) protects against necroptosis-specific TNF-induced systemic inflammatory response syndrome (SIRS) in vivo[1].
SZM679 (1 mg/kg; administered intragastrically; once daily for 7 days) improves cognitive function in STZ-induced AD mice[1].
SZM679 (1 mg/kg; administered intragastrically; once daily for 7 days) rescues brain structure damage with no obvious toxicity and decreases AD biomarkers and decreases the expression levels of inflammatory cytokines and inhibits RIPK1 phosphorylation in the brain tissues of AD mice[1].
| Animal Model: | Male C57BL/6 J mice with TNF-induced SIRS models[1] | | Dosage: | 10, 20, and 40 mg/kg | | Administration: | Intraperitoneal injection | | Result: | Protected mice in a dose-dependent manner from hypothermia and death. |
| Animal Model: | Male C57BL/6 J mice with AD models[1] | | Dosage: | 1 mg/kg | | Administration: | Administered intragastrically; once daily for 7 days | | Result: | Improved the anxiety, behavior, and exploratory ability of AD mice.
Improved the learning and memory ability of AD mice.
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| Animal Model: | Male C57BL/6 J mice with AD models[1] | | Dosage: | 1 mg/kg | | Administration: | Administered intragastrically; once daily for 7 days | | Result: | Rescued the damaged hippocampal structure of AD mice and restored the cell number and morphology.
Down-regulated the expression of the inflammatory cytokines, the IL-1β and TNF-α levels.
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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