PD173074

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

PD173074  纯度: 99.70%

PD173074 是有效的 FGFR1 抑制剂,IC50 为 25 nM;也可抑制 VEGFR2 的活性,IC50 值为 100-200 nM,对 FGFR1 的活性是 PDGFR 和 c-Src 的1000多倍。

PD173074

PD173074 Chemical Structure

CAS No. : 219580-11-7

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ¥634 In-stock
5 mg ¥550 In-stock
10 mg ¥800 In-stock
50 mg ¥2900 In-stock
100 mg ¥4900 In-stock
200 mg ¥7900 In-stock
500 mg   询价  
1 g   询价  

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生物活性

PD173074 is a potent FGFR1 inhibitor with an IC50 of 25 nM and also inhibits VEGFR2 with an IC50 of 100-200 nM, showing 1000-fold selectivity for FGFR1 over PDGFR and c-Src.

IC50 & Target[1]

FGFR1

25 nM (IC50)

VEGFR2

100 nM (IC50)

体外研究
(In Vitro)

PD 173074 inhibits autophosphorylation of FGFR1 in a dose-dependent manner with an IC50 in the range 1-5 nM. PD 173074 is an ATP-competitive inhibitor of FGFR1 with an inhibitory constant (Ki) of 40 nM[1]. PD 173074 and SU 5402 produce concentration-dependent reductions in FGF-2 enhancement of granule neuron survival, with IC50 values of 8 nM and 9 μM, respectively. PD 173074 does not inhibit neurotrophic and neuritogenic actions of FGF-2 signalling molecules in cerebellar granule neurons. PD 173074 and SU 5402 concentration-dependently inhibits the neurite growth response, when tested on FGF-2-treated granule neurons growing on polylysine/laminin, with IC50s of 22 nM and 25 μM, respectively[2]. PD173074 effectively antagonizes the effect of FGF-2 on proliferation and differentiation of OL progenitors in culture. Mitogen-activated protein kinase (MAPK) activation, a downstream event after activation of either FGFR or PDGFR, is also blocked by PD173074 in OL progenitors stimulated with FGF-2 but not PDGF[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

PD 173074 (1 mg/kg, i.p.) exhibits dose-dependent inhibition of FGF-induced neovascularization and angiogenesis in mice[1]. D173074 (25 mg/kg, p.o.) significantly inhibits tumor growth in mice[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

分子量

523.67

Formula

C28H41N7O3

CAS 号

219580-11-7

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : ≥ 52 mg/mL (99.30 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.9096 mL 9.5480 mL 19.0960 mL
5 mM 0.3819 mL 1.9096 mL 3.8192 mL
10 mM 0.1910 mL 0.9548 mL 1.9096 mL

*

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, 6 months; -20°C, 1 month。-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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (4.77 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.77 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (4.77 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.77 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

  • 3.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.08 mg/mL (3.97 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.97 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Mohammadi M, et al. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 1998 Oct 15;17(20):5896-904.

    [2]. Skaper SD, et al. The FGFR1 inhibitor PD 173074 selectively and potently antagonizes FGF-2 neurotrophic and neurotropic effects. J Neurochem. 2000 Oct;75(4):1520-7.

    [3]. Bansal R, et al. Specific inhibitor of FGF receptor signaling: FGF-2-mediated effects on proliferation, differentiation, and MAPK activation are inhibited by PD173074 in oligodendrocyte-lineage cells. J Neurosci Res. 2003 Nov 15;74(4):486-93.

    [4]. Trudel S, et al. Inhibition of fibroblast growth factor receptor 3 induces differentiation and apoptosis in t(4;14) myeloma. Blood. 2004 May 1;103(9):3521-8.

    [5]. Mahe M, et al. An FGFR3/MYC positive feedback loop provides new opportunities for targeted therapies in bladder cancers. EMBO Mol Med. 2018 Apr;10(4). pii: e8163.

    [6]. Zheng Y, et al. Inhibition of FGFR Signaling With PD173074 Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Rescues BMPR-II Expression. J Cardiovasc Pharmacol. 2015 Nov;66(5):504-14.

Cell Assay
[1]

An NIH 3T3 cell line overexpressing VEGFR2 (Flk-1) has been described previously. This cell line also expresses FGFR1 endogenously. Cells (1×106) in DMEM supplemented with 10% calf serum are seeded in 10 cm2 dishes and allowed to grow for 48 h. The medium is then removed and the cells are made quiescent in starvation medium (DMEM with 0.1% calf serum). After 18 h, the cells are incubated for 5 min with various concentrations of PD 173074 prepared in starvation medium. The cells are then stimulated with growth factor [VEGF (100 ng/mL) or aFGF (100 ng/mL) and heparin (10 µg/mL)] for 5 min at 37°C. The cells are washed with ice-cold PBS and lysed in 1 mL of lysis buffer (25 mM HEPES pH 7.5, 150 mM NaCl, 1% Triton X-100, 10% glycerol, 1 mM EGTA, 1.5 mM MgCl2, 1 mM PMSF, 10 µg/mL aprotonin, 10 µg/mL leupeptin) containing phosphatase inhibitor (0.2 mM Na3VO4). For inhibition studies of FGFR1, cell lysates are immunoprecipitated with antibodies to FGFR1, and then analyzed by SDS-PAGE and immunoblotting with antibodies to phosphotyrosine. For inhibition studies of VEGFR2, cell lysates (20 µL) are analyzed directly by SDS-PAGE and immunoblotted with antibodies to phosphotyrosine.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[4]

Six-week-old athymic nude mice are inoculated subcutaneously with 3×105 NIH 3T3 cells expressing Y373C FGFR3 and Ras V12. Intraperitoneal injections of either 20 mg/kg PD173074 or 0.05 mol/Llactic acid buffer are initiated on the day of tumor injection and continued for 9 days. Ten mice for each experiment are included.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Mohammadi M, et al. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 1998 Oct 15;17(20):5896-904.

    [2]. Skaper SD, et al. The FGFR1 inhibitor PD 173074 selectively and potently antagonizes FGF-2 neurotrophic and neurotropic effects. J Neurochem. 2000 Oct;75(4):1520-7.

    [3]. Bansal R, et al. Specific inhibitor of FGF receptor signaling: FGF-2-mediated effects on proliferation, differentiation, and MAPK activation are inhibited by PD173074 in oligodendrocyte-lineage cells. J Neurosci Res. 2003 Nov 15;74(4):486-93.

    [4]. Trudel S, et al. Inhibition of fibroblast growth factor receptor 3 induces differentiation and apoptosis in t(4;14) myeloma. Blood. 2004 May 1;103(9):3521-8.

    [5]. Mahe M, et al. An FGFR3/MYC positive feedback loop provides new opportunities for targeted therapies in bladder cancers. EMBO Mol Med. 2018 Apr;10(4). pii: e8163.

    [6]. Zheng Y, et al. Inhibition of FGFR Signaling With PD173074 Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Rescues BMPR-II Expression. J Cardiovasc Pharmacol. 2015 Nov;66(5):504-14.

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