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当前位置: 首页 > 产品中心 > Small_molecule > Medchemexpress/Reparixin(同义词:Rerectaxin;DF 1681Y)/HY-15251/25mg
商品详细Medchemexpress/Reparixin(同义词:Rerectaxin;DF 1681Y)/HY-15251/25mg
Medchemexpress/Reparixin(同义词:Rerectaxin;DF 1681Y)/HY-15251/25mg
Medchemexpress/Reparixin(同义词:Rerectaxin;DF 1681Y)/HY-15251/25mg
商品编号: HY-15251-10mM*1mLinDMSO
品牌: MedChemExp
市场价: ¥3360.00
美元价: 2016.00
产地: 美国(厂家直采)
公司:
产品分类: 小分子
公司分类: Small_molecule
联系Q Q: 3392242852
电话号码: 4000-520-616
电子邮箱: info@ebiomall.com
商品介绍
Reparixin is a potent inhibitor of both CXCL8 receptors CXCR1/2, it inhibits weakly CXCR2-mediated cell migration (IC50=100 nM), whereas it strongly blocks CXCR1-mediated chemotaxis (IC50=1 nM).

Customer Validation

  • Ann Rheum Dis. 2016 Apr;75(4):730-8.
  • Nat Commun. 2017 May 26;8:15584.
  • Cell Death Dis. 2017 Jul 13;8(7):e2932.
  • Stem Cells. 2015 Dec;33(12):3558-68.
  • Biochim Biophys Acta. 2017 Jan;1863(1):220-230.
  • Oncotarget. 2017 Jul 21;8(36):60210-60222.
  • Oncogenesis. 2016 Jun 13;5(6):e234.
  • J Gastroenterol Hepatol. 2017 May 8.
  • Vet Immunol Immunopathol. 2016 Dec;182:52-58.
Description

Reparixin is a potent inhibitor of both CXCL8 receptors CXCR1/2, it inhibits weakly CXCR2-mediated cell migration (IC50=100 nM), whereas it strongly blocks CXCR1-mediated chemotaxis (IC50=1 nM).

IC50 & Target

IC50: 5.6/80 nM (CXCR1wt/CXCR1Ile43Val, in L1.2 cell)[1]

In Vitro

Reparixin is a potent functional inhibitor of CXCL8-induced biological activities on human PMNs with a marked selectivity (around 400-fold) for CXCR1, as shown in specific experiments on CXCR1/L1.2 and CXCR2/L1.2 transfected cells and on human PMNs. The efficacy of Reparixin is significantly lower in L1.2 cells expressing Ile43Val CXCR1 mutant (IC50 values of 5.6 nM and 80 nM for CXCR1 wt and CXCR1 Ile43Val, respectively)[1]. Reparixin is a non-competitive allosteric inhibitor of IL-8 receptors with a 400-fold higher efficacy in inhibiting CXCR1 activity than CXCR2[2].

In Vivo

Reparixin is an inhibitor of CXCL8 receptor CXCR1 and CXCR2 activation, has been shown to attenuate inflammatory responses in various injury models. Spontaneously hypertensive rats (SHR) are administered a subcutaneous injection of Reparixin (5 mg/kg) daily for 3 weeks. Reparixin effectively decreases systolic blood pressure and increased the blood flow[3]. Reparixin reduces the levels of IL-1β in the brain after middle cerebral artery occlusion/reperfusion (MCAo) in mice. Bars represent levels of IL-1β (pg/100 mg) measured by ELISA in the brain tissues of mice subjected or not (SHAM) to MCAo and pretreated with vehicle or Reparixin (30 mg/kg, s.c.)[4].

References
  • [1]. Moriconi A, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.

    [2]. Bertini R, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.

    [3]. Kim HY, et al. Reparixin, an inhibitor of CXCR1 and CXCR2 receptor activation, attenuates blood pressure and hypertension-related mediators expression in spontaneously hypertensive rats. Biol Pharm Bull. 2011;34(1):120-7.

    [4]. Sousa LF, et al. Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice. Clinics (Sao Paulo). 2013;68(3):391-4.

    [5]. Krishnamurthy A, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016 Apr;75(4):721-9.

Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 3.5287 mL 17.6435 mL 35.2871 mL
5 mM 0.7057 mL 3.5287 mL 7.0574 mL
10 mM 0.3529 mL 1.7644 mL 3.5287 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

Reparixin is dissolved in saline at the appropriate dilution[1].

L1.2 Cell suspension (1.5-3×106 cells/mL) is incubated at 37°C for 15 min in the presence of vehicle or of Reparixin (1 nM-1μM) and next seeded in triplicates in the upper compartment of the chemotactic chamber. Different agonists are seeded in the lower compartment of the chamber at the following concentrations: 1 nM CXCL8, 0.03 nM fMLP, 10 nM CXCL1, 2.5 nM CCL2, 30 nM C5a. The chemotactic chamber is incubated at 37°C in air with 5% CO2 for 45 min (human PMNs) or 2 h (monocytes). At the end of incubation, the filter is removed, fixed, and stained and five oil immersion fields at high magnification (100×) are counted for each migration well after sample coding. L1.2 migration is evaluated using 5 μm pore size Transwell filters[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[3][4]

Reparixin is dissolved in saline and administered subcutaneously (Mice and Rat).

Rat[3]
The Reparixin-treated group contained 5 SHR (SHR-R), where equal numbers of normal saline-treated SHR (SHR-N) and WKY (WKY-N) served as controls. Eighteen-week-old SHR received a subcutaneous injection of Reparixin (5 mg/kg) once per day for 3 weeks. Reparixin effects on blood flow, blood pressure and body weight are measured before treatment and then weekly until 1 week after the final injection. The effect of Reparixin on the expression of hypertension-related mediators in thoracic aortas, as well as nitric oxide (NO) plasma levels, is examined 1 week after the final injection. At the end of the 4 week period, both control and Reparixin-treated rats are anesthetized via intraperitoneal injection of thiopental (50 mg/kg), and blood and tissue samples are collected.
Mice[4]
C57BL/6J mice (8-10 weeks old/20-25 g) are used. The subcutaneous administration of Reparixin (30 mg/kg) is performed 60 minutes before cerebral ischemia induction. The animals are divided into the following three experimental groups: Sham (i.e., the group in which the arteries are visualized, but there is no occlusion of the middle cerebral artery), Vehicle (i.e., the group pre-treated with the vehicle, phosphate buffer solution, 60 minutes before MCAo) and Reparixin (i.e., the group pre-treated with the drug 60 minutes before MCAo). To evaluate neurological signs secondary to MCAo, the animals are assessed with the SHIRPA battery 24 h after reperfusion. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
  • [1]. Moriconi A, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.

    [2]. Bertini R, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.

    [3]. Kim HY, et al. Reparixin, an inhibitor of CXCR1 and CXCR2 receptor activation, attenuates blood pressure and hypertension-related mediators expression in spontaneously hypertensive rats. Biol Pharm Bull. 2011;34(1):120-7.

    [4]. Sousa LF, et al. Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice. Clinics (Sao Paulo). 2013;68(3):391-4.

    [5]. Krishnamurthy A, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016 Apr;75(4):721-9.

Molecular Weight

283.39

Formula

C₁₄H₂₁NO₃S

CAS No.

266359-83-5

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 500 mg/mL

Reparixin is prepare in vehicle (sterile saline)[5].

* "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

References
  • [1]. Moriconi A, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.

    [2]. Bertini R, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.

    [3]. Kim HY, et al. Reparixin, an inhibitor of CXCR1 and CXCR2 receptor activation, attenuates blood pressure and hypertension-related mediators expression in spontaneously hypertensive rats. Biol Pharm Bull. 2011;34(1):120-7.

    [4]. Sousa LF, et al. Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice. Clinics (Sao Paulo). 2013;68(3):391-4.

    [5]. Krishnamurthy A, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016 Apr;75(4):721-9.

Purity: 99.88% ee.: 100.00%

Data Sheet (124 KB) SDS (120 KB)

COA (94 KB) HNMR (178 KB) RP-HPLC (194 KB) NP-HPLC (194 KB) MS (220 KB)

Handling Instructions (1252 KB)
  • [1]. Moriconi A, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.

    [2]. Bertini R, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.

    [3]. Kim HY, et al. Reparixin, an inhibitor of CXCR1 and CXCR2 receptor activation, attenuates blood pressure and hypertension-related mediators expression in spontaneously hypertensive rats. Biol Pharm Bull. 2011;34(1):120-7.

    [4]. Sousa LF, et al. Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice. Clinics (Sao Paulo). 2013;68(3):391-4.

    [5]. Krishnamurthy A, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016 Apr;75(4):721-9.

品牌介绍
托烷司琼临床评价药物相关作用适应症托烷司琼CAS号:89565-68-4英文名称:Tropisetron英文同义词:icf205-930;TROPICACID;TROPISETRON;SS-TROPISETRON;BETA-TROPISETRON;Tropisetron(ICS205930);TROPISHTRONHYDROCHLORIDE;Indole-3-carbonylchloride;3-Tropanylindole-3-carboxylate;lαH,5Αh-Tropan-3α-ylindole-3-carboxylate中文名称:托烷司琼中文同义词:托普西隆;托普西龙;曲匹西龙;托烷司琼;Β-托烷司琼;CS-348;Β-内托烷司琼;吲哚-3-甲酰氯;Β-托烷司琼(光学异构体);Β-托烷司琼,托烷司琼异构体CBNumber:CB3236404分子式:C17H20N2O2分子量:284.35MOLFile:89565-68-4.mol化学性质安全信息用途供应商112化学性质安全信息用途供应商112托烷司琼化学性质熔点:201-202°C沸点:448.5±35.0°C(Predicted)密度:1.26储存条件:2-8°C溶解度:H2O:soluble形态:solid酸度系数(pKa):15.38±0.30(Predicted)颜色:whiteCAS数据库:Chemicalbook89565-68-4(CASDataBaseReference)安全信息WGKGermany:3托烷司琼化学药品说明书托烷司琼|药物应用信息托烷司琼性质、用途与生产工艺临床评价Sorbe等报道本品对含顺铂(剂量50~89mg/m2)化疗方案引起的急性呕吐完全控制率为63%。58例恶性肿瘤化疗所致恶心、呕吐者,应用托烷司琼或昂丹司琼8mg分别在同一病人前后2个化疗周期的第1d给药前30min静脉注射,并用地塞米松10mg静脉滴注。结果两药控制急性及迟发性恶心、呕吐的疗效基本相似,均可达81%~100%。本品对强致吐化疗药物顺铂的止吐疗效突出。药物相关作用饮食可略为延长本品的吸收。本品与利福平、苯巴比妥等肝酶诱导药同时使用,可加快代谢,故快代谢型者需增加剂量,慢者则不必。西咪替丁等肝酶抑制药对本品血药浓度无明显影响。适应症托烷司琼临床用于预防和治疗癌症化疗引起的恶心和呕吐。化学性质结晶,熔点201-202℃(二氯甲烷-乙酸乙酯)。单盐酸托烷司琼(TropisetronMonohydroehloride):C17H20N2O2?HCI。[105826-92-4]。熔点283-285℃(分解)。用途有高效性和选择性的5-HT3受体拮抗剂。用于化疗所致的呕吐。用途为5-羟色胺拮抗药生产方法托品醇(I)和酰氯(Ⅱ)反应,可得托烷司琼。托烷司琼上下游产品信息上游原料托品醇下游产品