Dapansutrile

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Chemical Structure| 54863-37-5 同义名 : 3-methanesulfonyl Propanenitrile
CAS号 : 54863-37-5
货号 : A867292
分子式 : C4H7NO2S
纯度 : 98%+
分子量 : 133.169
MDL号 : MFCD11934305
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(788.47 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 35 mg/mL(262.82 mM)，配合低频超声助溶
动物实验配方：
生物活性
描述 NLRP3 inflammasome can be widely found in epithelial cells and immune cells. The NOD-like receptors (NLRs) family member NLRP3 contains a central nucleotide-binding and oligomerization (NACHT) domain which facilitates self-oligomerization and has ATPase activity[1]. Dapansutrile（OLT1177） is a potent, selective and orally active inhibitor of NLRP3 inflammasome. Anti-inflammatory, analgesic activity[2]. OLT1177 specifically inhibited both canonical and noncanonical NLRP3 inflammasome activation in vitro, and showed no effect on the AIM2 and NLRC4 inflammasomes. OLT1177 reduced caspase-1 activity and IL-1β production in monocytes from patients with CAPS and alleviated the severity of LPS-induced systemic inflammation in vivo. Importantly, no biochemical or hematological adverse effects were observed in humans receiving a high concentration of OLT1177 for 8 days. Like CY-09, OLT1177 exerts its anti-inflammatory effect on NLRP3 inflammasome activation independently of signal 1 (NLRP3 and pro-IL-1β expression) or K+ efflux,but directly binds to NLRP3 and inhibits ATPase activity[3]. In vivo, tumor-associated NLRP3/IL-1 signaling induced expansion of myeloid-derived suppressor cells (MDSCs), leading to reduced natural killer and CD8+ T cell activity concomitant with an increased presence of regulatory T (Treg) cells in the primary tumors. Either genetic or pharmacological inhibition of tumor-derived NLRP3 by dapansutrile (OLT1177) was sufficient to reduce MDSCs expansion and to enhance antitumor immunity, resulting in reduced tumor growth[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

7.51mL

1.50mL

0.75mL

37.55mL

7.51mL

3.75mL

75.09mL

15.02mL

7.51mL
参考文献

[1] Yu Zhen, Hu Zhang. NLRP3 Inflammasome and Inflammatory Bowel Disease. Front Immunol. 2019 Feb 28;10:276.

[2]Toldo S, et al. The NLRP3 Inflammasome Inhibitor, Dapansutrile, Reduces Infarct Size and Preserves Contractile Function After Ischemia Reperfusion Injury in the Mouse. J Cardiovasc Pharmacol. 2019 Apr;73(4):215-222.

[3] Marchetti, C. et al. OLT1177, a β-sulfonyl nitrile compound, safe in humans,inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc. Natl. Acad. Sci. USA 115, 89 (2018).

[4] Isak W Tengesdal, Dinoop R Menon,et al. Targeting tumor-derived NLRP3 reduces melanoma progression by limiting MDSCs expansion. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2000915118.