Nexinhib20是一种中性粒细胞胞吐抑制剂，靶向Rab27a-JFC1结合的IC50值为2.6µM。
Cas No.:331949-35-0
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Nexinhib20 is an inhibitor of neutrophil exocytosis, with an IC50 value of 2.6μM for targeting Rab27a-JFC1 binding [1]. Nexinhib20 limits β2 integrin mobilization and availability at the cell surface while indirectly affecting active integrin avidity [2]. Nexinhib20 has been widely used to inhibit neutrophil adhesion and β2 integrin activation[3].
In vitro, Nexinhib20 treatment for 48 hours significantly inhibited the viability of N417 cells, H524 cells, and N417 H889 cells, with IC50 values of 12.91μM, 1.55μM and 8.58μM, respectively[4]. Treatment with 5μM Nexinhib20 for 48 hours enhanced the immunosuppressive function of eosinophils derived from patients with allergic rhinitis (AR)[5]. Treatment with 10μM Nexinhib20 for 15 minutes reversed the increase in FcgRI in neutrophils stimulated by heat-aggregated IgG and inhibited the production of ROS[6].
In vivo, Nexinhib20 treatment via intraperitoneal injection at a dose of 20mg/kg, twice a week for 4 weeks, significantly inhibited tumor growth in a mouse xenograft model derived from pancreatic ductal adenocarcinom[7]. Intraperitoneal injection of a single dose of Nexinhib20 (100mM in 10μl DMSO) 30 minutes before reperfusion inhibited the recruitment of neutrophils and significantly reduced the infarct area in mice after myocardial ischemia/reperfusion injury[8].
References:
[1] Johnson J L, Ramadass M, He J, et al. Identification of neutrophil exocytosis inhibitors (Nexinhibs), small molecule inhibitors of neutrophil exocytosis and inflammation: druggability of the small GTPase Rab27a[J]. Journal of Biological Chemistry, 2016, 291(50): 25965-25982.
[2] Askari K, Johnson J L, Shukla A, et al. Nexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1[J]. Journal of Leukocyte Biology, 2025, 117(4): qiaf012.
[3] Fan Z, Liu W, Cronin C G, et al. Nexinhib20 prevents myocardial ischemia‐reperfusion injury by inhibiting neutrophil adhesion and β2 integrin activation[J]. The FASEB Journal, 2022, 36.
[4] Irep N, Inci K, Tokgun P E, et al. Exosome inhibition improves response to first‐line therapy in small cell lung cancer[J]. Journal of Cellular and Molecular Medicine, 2024, 28(4): e18138.
[5] Liao Y, Li M, Song S, et al. The Immunosuppressive Functions of Eosinophils Are Compromised in Patients With Allergic Rhinitis, Particularly Concerning Rab27a Expression[J]. Immunity, Inflammation and Disease, 2024, 12(12): e70091.
[6] Huot S, Laflamme C, Fortin P R, et al. IgG‐aggregates rapidly upregulate FcgRI expression at the surface of human neutrophils in a FcgRII‐dependent fashion: a crucial role for FcgRI in the generation of reactive oxygen species[J]. The FASEB Journal, 2020, 34(11): 15208-15221.
[7] Ruivo C F, Bastos N, Adem B, et al. Extracellular vesicles from pancreatic cancer stem cells lead an intratumor communication network (EVNet) to fuel tumour progression[J]. Gut, 2022, 71(10): 2043-2068.
[8] Liu W, Cronin C G, Cao Z, et al. Nexinhib20 Inhibits Neutrophil Adhesion and β2 Integrin Activation by Antagonizing Rac-1–Guanosine 5′-Triphosphate Interaction[J]. The Journal of Immunology, 2022, 209(8): 1574-1585.
Nexinhib20是一种中性粒细胞胞吐抑制剂，靶向Rab27a-JFC1结合的IC50值为2.6µM [1]。Nexinhib20限制β2整合素在细胞表面的动员和可用性，同时间接影响活性整合素的亲和力[2]。Nexinhib20已被广泛用于抑制中性粒细胞粘附和β2整合素激活[3]。
在体外，Nexinhib20处理48小时显著抑制了N417细胞、H524细胞和N417 H889细胞的活力，IC50值分别为12.91µM、1.55µM和8.58µM[4]。使用5µM的Nexinhib20处理48小时，增强了来自过敏性鼻炎（AR）患者嗜酸性粒细胞的免疫抑制功能[5]。使用10µM的Nexinhib20处理15分钟，逆转了热聚集IgG刺激的中性粒细胞中FcgRI的增加，并抑制了ROS的产生[6]。
在体内，每周两次腹腔注射20mg/kg剂量的Nexinhib20，持续4周，显著抑制了胰腺导管腺癌来源的小鼠异种移植模型中的肿瘤生长[7]。在再灌注前30分钟给小鼠单次腹腔注射Nexinhib20（100mM；溶于10µl DMSO），抑制了中性粒细胞的募集，并显著减少了心肌缺血/再灌注损伤后的梗死面积[8]。
| Cell experiment [1]: | |
Cell lines | N417 cells |
Preparation Method | N417 cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. Cells were cultured in an incubator at 37°C and 5% CO2. The cells were seeded at a density of 1×104 cells per well in a 96-well plate and treated with different concentrations of Nexinhib20 (0, 1, 2.5, 5, 7.5, 10, and 20μM) at 37°C for 48 hours. Then, the cell viability was analyzed. |
Reaction Conditions | 0, 1, 2.5, 5, 7.5, 10, and 20μM; 48h |
Applications | Nexinhib20 treatment reduced the cell viability of N417 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | C57BL/6J wild-type mice |
Preparation Method | C57BL/6J wild-type mice were housed in a standard animal room with a standard rodent chow diet. Mice were subjected to 35 minutes of myocardial ischemia and 1 hour (for multi-photon microscopy and flow cytometry) or 22-26 hours of reperfusion. Nexinhib20 (100mM; 10μl in DMSO per mouse) or vehicle control was administered i.p. 30 minutes before reperfusion. After occlusion for 35 minutes, reperfusion was initiated by releasing the ligature and removing the PE-10 tubing. The chest wall was closed, the mice were extubated, and body temperature was maintained by use of a 37°C warm pad. Hearts were harvested 1 or 22-26 hours later for analysis. |
Dosage form | 100mM (in 10μl DMSO) for once; i.p. |
Applications | Nexinhib20 treatment significantly decreased infarct size after myocardial ischemia-reperfusion injury in mice. |
References: | |
| Cas No. | 331949-35-0 | SDF | |
| 化学名 | 4,4-dimethyl-1-(3-nitrophenyl)-2-(1H-1,2,4-triazol-1-yl)-1-penten-3-one | ||
| Canonical SMILES | O=C(C(C)(C)C)/C(N1N=CN=C1)=C/C2=CC([N+]([O-])=O)=CC=C2 | ||
| 分子式 | C15H16N4O3 | 分子量 | 300.3 |
| 溶解度 | 15mg/mL in ethanol, 30mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.33 mL | 16.65 mL | 33.3 mL |
| 5 mM | 666 μL | 3.33 mL | 6.66 mL |
| 10 mM | 333 μL | 1.665 mL | 3.33 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet