FR 180204是一种选择性的ERK抑制剂，对ERK1和ERK2的IC50值分别为0.51μM和0.33μM。
Cas No.:865362-74-9
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');)
FR 180204 is a selective ERK inhibitor with IC50 values of 0.51μM and 0.33μM for ERK1 and ERK2, respectively [1]. FR 180204 can induce the activation of AP-1 by TGF-β (IC50=3.1µM), and inhibit the activity of ERK by binding to the Q105, D106, L156, and C166 sites of the active pocket [2]. FR 180204 has been widely used to inhibit endothelial cell migration and angiogenesis[3].
In vitro, FR 180204 treatment for 48 hours significantly inhibited the viability of DLD-1 cells and LoVo cells, with IC50 values of 150µM and 40µM, respectively[4]. Treatment with 50µM FR 180204 for 16 hours significantly inhibited the activity of heme oxygenase (HO) and lactate dehydrogenase in mouse glial cortical cells[5].
In vivo, FR 180204 treatment via intraperitoneal injections at a dose of 100mg/kg (twice a day) for 12 days ameliorated collagen-induced arthritis in mice and decreased weight loss[6]. Intravenous injection of FR 180204 at a dose of 50mg/kg at 1 hour before, 1 hour after, and 24 hours after dengue virus (DENV) infection significantly ameliorated DENV-induced liver injury and hematological parameters in Balb/c mice [7]. Continuous intraperitoneal injection of a 100mg/kg/day dose of FR 180204 for one week significantly alleviated myocardial hypertrophy induced by isoproterenol (ISO) in Pak-1 knockout mice[8].
References:
[1] Lee C J, Lee H S, Ryu H W, et al. Abstract A24: Targeting of ERKs with magnolin inhibits EGF-induced anchorage-independent cell transformation[J]. Cancer Prevention Research, 2013, 6(11_Supplement): A24-A24.
[2] Ohori M, Kinoshita T, Okubo M, et al. Identification of a selective ERK inhibitor and structural determination of the inhibitor–ERK2 complex[J]. Biochemical and biophysical research communications, 2005, 336(1): 357-363.
[3] Xue S, Tang H, Zhao G, et al. CC Motif Chemokine 8 promotes angiogenesis in vascular endothelial cells[J]. Vascular, 2021, 29(3): 429-441.
[4] Saglam A S Y, Alp E, Elmazoglu Z, et al. Effect of API-1 and FR180204 on cell proliferation and apoptosis in human DLD-1 and LoVo colorectal cancer cells[J]. Oncology Letters, 2016, 12(4): 2463-2474.
[5] Chen-Roetling J, Li Z, Chen M, et al. Heme oxygenase activity and hemoglobin neurotoxicity are attenuated by inhibitors of the MEK/ERK pathway[J]. Neuropharmacology, 2009, 56(5): 922-928.
[6] Ohori M, Takeuchi M, Maruki R, et al. FR180204, a novel and selective inhibitor of extracellular signal-regulated kinase, ameliorates collagen-induced arthritis in mice[J]. Naunyn-Schmiedeberg's archives of pharmacology, 2007, 374(4): 311-316.
[7] Sreekanth G P, Chuncharunee A, Sirimontaporn A, et al. Role of ERK1/2 signaling in dengue virus-induced liver injury[J]. Virus research, 2014, 188: 15-26.
[8] Taglieri D M, Monasky M M, Knezevic I, et al. Ablation of p21-activated kinase-1 in mice promotes isoproterenol-induced cardiac hypertrophy in association with activation of Erk1/2 and inhibition of protein phosphatase 2A[J]. Journal of molecular and cellular cardiology, 2011, 51(6): 988-996.
FR 180204是一种选择性的ERK抑制剂，对ERK1和ERK2的IC50值分别为0.51μM和0.33μM[1]。FR 180204可诱导TGF-β激活AP-1 (IC50=3.1µM)，并通过结合活性口袋的Q105、D106、L156和C166位点来抑制ERK活性[2]。FR 180204已被广泛用于抑制内皮细胞迁移和血管生成[3]。
在体外，FR 180204处理DLD-1细胞和LoVo细胞48小时，显著抑制了细胞活力，IC50值分别为150μM和40μM[4]。50μM的FR 180204处理小鼠胶质皮质细胞16小时，显著抑制了血红素加氧酶(HO)和乳酸脱氢酶的活性[5]。
在体内，腹腔注射100mg/kg剂量的FR 180204（每日两次），连续12天，改善了胶原诱导的小鼠关节炎，并减少了体重下降[6]。在登革热病毒(DENV)感染前1小时、感染后1小时和感染后24小时分别静脉注射50mg/kg剂量的FR 180204，显著改善了DENV诱导的Balb/c小鼠肝损伤和血液学参数[7]。连续一周每日腹腔注射100mg/kg剂量的FR 180204，显著减轻了isoproterenol (ISO)诱导的Pak-1敲除小鼠的心肌肥厚[8]。
| Cell experiment [1]: | |
Cell lines | LoVo cells |
Preparation Method | LoVo cells were seeded in 96-well plates at a density of 1×104 cells in RPMI-1640 medium with 10% (v/v) fetal bovine serum (FBS), 2mM L-glutamine, 100U/ml penicillin, and 100µg/ml streptomycin in a humidified atmosphere containing 5% CO2. After 48h of treatment with different concentrations of FR 180204 (1, 5, 10, 20, 50, 100, and 150µM), the cell viability was measured. |
Reaction Conditions | 1, 5, 10, 20, 50, 100, and 150µM; 48h |
Applications | FR 180204 treatment significantly inhibited the cell viability of LoVo cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male DBA/1 mice |
Preparation Method | Male DBA/1 mice (6 weeks old; 22-25g) were housed in a clean atmosphere with a 12-h light/dark cycle and fed with standard rodent chow ad libitum. Bovine CII was dissolved in 0.1M acetic acid at a concentration of 10mg/ml and then emulsified in an equal volume of Freund’s complete adjuvant H37Rv. Apart from a naive group, each mouse was immunized with 25μl of the CII emulsion into the tail base, followed by a boost injection 3 weeks after primary injection. FR 180204 and methylprednisolone were ground and suspended in 0.1% methylcellulose solution to a volume of 5ml/kg. Intraperitoneal injections of a 100mg/kg dose of FR 180204 (twice a day) for 12 days, and the arthritis status of the mice was analyzed. |
Dosage form | 100mg/kg; twice a day for 12 days; i.p. |
Applications | FR 180204 treatment significantly ameliorated the clinical arthritis in mice. |
References: | |
| Cas No. | 865362-74-9 | SDF | |
| 别名 | ERK Inhibitor II | ||
| 化学名 | 5-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridazin-3-amine | ||
| Canonical SMILES | C1=CC=C(C=C1)C2=NN3C=CC=CC3=C2C4=NN=C5C(=C4)C(=NN5)N | ||
| 分子式 | C18H13N7 | 分子量 | 327.34 |
| 溶解度 | ≥ 10.25mg/mL in DMSO, ≥ 4.47 mg/mL in EtOH with ultrasonic | 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 | 3.0549 mL | 15.2746 mL | 30.5493 mL |
| 5 mM | 611 μL | 3.0549 mL | 6.1099 mL |
| 10 mM | 305.5 μL | 1.5275 mL | 3.0549 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