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.
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PD173074 Chemische Struktur
CAS. Nr. : 219580-11-7
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Western blot analysis of MYC and FGFR3 expression in lysates from MGH-U3 and RT112 cells treated with (+)-JQ1 (1 or 4 μM) for 48 h. Anti-actin antibody is used as a loading control. Pan-FGFR inhibitor, PD173074 (50 nM and 1 μM), and inactive enantiomer (-)-JQ1 (4 μM) are used as controls.
The effects of PD173074 on expression and activation of Akt, Erk1/2, PCNA, and caspase-3 representative immunoblots of Akt, Erk1/2, PCNA, a-SMA, cleaved caspase-3, Bcl-2, and Bax. GAPDH is a loading control.
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Alle FGFR Isoform-spezifische Produkte anzeigen:
Alle Isoformen anzeigen
FGFR FGFR1 FGFR2 FGFR3 FGFR4 FGF21
Alle VEGFR Isoform-spezifische Produkte anzeigen:
Alle Isoformen anzeigen
VEGFR1/Flt-1 VEGFR2/KDR/Flk-1 VEGFR3/Flt-4
Beschreibung
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)
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PD173074 Related Antibodies
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Speicherung
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
1 year
-20°C
6 months
Lösungsmittel & Löslichkeit
In Vitro:
DMSO : ≥ 100 mg/mL (190.96 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
*"≥" means soluble, but saturation unknown.
Preparing Stock Solutions
ConcentrationSolventMass
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
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (4.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
Protocol 3
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[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.
[Content Brief]
[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.
[Content Brief]
[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.
[Content Brief]
[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.
[Content Brief]
[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.
[Content Brief]
[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.
[Content Brief]
Zellassay
[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.
MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Tierverwaltung
[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.
MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Verweise
[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.
[Content Brief]
[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.
[Content Brief]
[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.
[Content Brief]
[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.
[Content Brief]
[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.
[Content Brief]
[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.
[Content Brief]
[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.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
1.9096 mL
9.5480 mL
19.0960 mL
47.7400 mL
5 mM
0.3819 mL
1.9096 mL
3.8192 mL
9.5480 mL
10 mM
0.1910 mL
0.9548 mL
1.9096 mL
4.7740 mL
15 mM
0.1273 mL
0.6365 mL
1.2731 mL
3.1827 mL
20 mM
0.0955 mL
0.4774 mL
0.9548 mL
2.3870 mL
25 mM
0.0764 mL
0.3819 mL
0.7638 mL
1.9096 mL
30 mM
0.0637 mL
0.3183 mL
0.6365 mL
1.5913 mL
40 mM
0.0477 mL
0.2387 mL
0.4774 mL
1.1935 mL
50 mM
0.0382 mL
0.1910 mL
0.3819 mL
0.9548 mL
60 mM
0.0318 mL
0.1591 mL
0.3183 mL
0.7957 mL
80 mM
0.0239 mL
0.1193 mL
0.2387 mL
0.5967 mL
100 mM
0.0191 mL
0.0955 mL
0.1910 mL
0.4774 mL
PD173074 Related Classifications
Protein Tyrosine Kinase/RTKApoptosis
FGFRVEGFRApoptosis
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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