PD173074
Catalog No.: GC17943Purity:>98.00%Synonyms: PD 173074,PD-173074
PD173074 is an ATP-competitive FGFR1 and VEGFR2 inhibitor with an IC50 value of 26nM and 100-200nM, respectively, showing higher selectivity for FGFR1 over PDGFR and c-Src.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 219580-11-7
10mM (in 1mL DMSO)In Stock
$48.00
1
10mgIn Stock
$37.00
1
50mgIn Stock
$104.00
1
500mgIn Stock
$577.00
1
1gIn Stock
$840.00
1
| Pack Size | Price | Availability | Quantity | Action |
|---|---|---|---|---|
| 10mM (in 1mL DMSO) | $48.00 | In Stock | 1 | |
| 10mg | $37.00 | In Stock | 1 | |
| 50mg | $104.00 | In Stock | 1 | |
| 500mg | $577.00 | In Stock | 1 | |
| 1g | $840.00 | In Stock | 1 |
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Citations
1 publicationsPublications from researchers using this productDescription
PD173074 is an ATP-competitive FGFR1 and VEGFR2 inhibitor with an IC50 value of 26nM and 100-200nM, respectively, showing higher selectivity for FGFR1 over PDGFR and c-Src[1]. PD173074 weakly inhibits the activities of Src, InsR, EGFR, PDGFR, MEK, and PKC[2].
in vitro, PD173074 (0.5, 1, 10, 20 and 50μM; 48h) blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells[3]. PD173074 (0.25 or 1µmol/L, 20µL/well; 4h)reverses MRP7 (ABCC10)-mediated multidrug resistance[4]. PD173074 (0-100μM; 30min) binds to the C-terminus of oncofetal architectural chromatin factor high-mobility group AT-hook 2 (HMGA2) and modulates its DNA-binding and transcriptional activation functions[5].
in vivo, PD173074 (50mg/kg; up to 28 days; goral gavage) blocks small cell lung cancer growth in a nude mice model[6]. PD173074 (20 mg/kg; 3 days; i.p)block FGFR-dependent urothelial carcinoma growth in a Balb/c mice model[7]. PD173074 (20mg/kg; once per day; 10 days; i.p) improves antitumor immunity and impairs breast cancer metastasis in a Balb/c mice model[8].
References:
[1] Dimitroff, C J et al. “Anti-angiogenic activity of selected receptor tyrosine kinase inhibitors, PD166285 and PD173074: implications for combination treatment with photodynamic therapy.” *Investigational new drugs* vol. 17,2 (1999): 121-35. doi:10.1023/a:1006367032156
[2] Tan, Li et al. “Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors.” *Proceedings of the National Academy of Sciences of the United States of America* vol. 111,45 (2014): E4869-77. doi:10.1073/pnas.1403438111
[3] Qiao, Chuchu et al. “PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells.” *PloS one* vol. 15,6 e0234708. 18 Jun. 2020, doi:10.1371/journal.pone.0234708
[4] Anreddy, Nagaraju et al. “PD173074, a selective FGFR inhibitor, reverses MRP7 (ABCC10)-mediated MDR.” *Acta pharmaceutica Sinica. B* vol. 4,3 (2014): 202-7. doi:10.1016/j.apsb.2014.02.003
[5] Ahmed, Syed Moiz et al. “The FGFR inhibitor PD173074 binds to the C-terminus of oncofetal HMGA2 and modulates its DNA-binding and transcriptional activation functions.” *FEBS letters* vol. 597,15 (2023): 1977-1988. doi:10.1002/1873-3468.14675
[6] Pardo, Olivier E et al. “The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo.” *Cancer research*vol. 69,22 (2009): 8645-51. doi:10.1158/0008-5472.CAN-09-1576
[7] Lamont, F R et al. “Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivo.” *British journal of cancer* vol. 104,1 (2011): 75-82. doi:10.1038/sj.bjc.6606016
[8] Ye, Tinghong et al. “Inhibition of FGFR signaling by PD173074 improves antitumor immunity and impairs breast cancer metastasis.” *Breast cancer research and treatment* vol. 143,3 (2014): 435-46. doi:10.1007/s10549-013-2829-y
Protocol
| Kinase experiment [1]: | |
Preparation Method | The assay media for TK activity contained 25mM HEPES buffer (pH 7.4), 150mM NaCl, 10mM MnCl2, 0.1mM sodium orthovanadate, 750µg/ml of random co-polymer of glutamic acid and tyrosine (4:1), various concentrations of inhibitor and 60–75ng of enzyme. The reaction (total volume, 100µL) was initiated by the addition of [γ-32P]ATP (50µM ATP containing 0.4µCi [32P]ATP per incubation. Samples were incubated for 10 minutes at 25℃ and terminated by the addition of 30% trichloroacetic acid. |
Reaction Conditions | 10 minutes at 25℃ |
Applications | PD173074 displayed selective inhibitory activity towards FGFR1TK at 26nM. |
| Cell experiment [2]: | |
Cell lines | HepG2, Hep3B, human normal liver cell line HL7702 |
Preparation Method | HepG2, Hep3B or HL7702 cells were seeded into 96-well plate at 5000cells/well. After adherence, the cells were treated with different concentrations of PD173074 (0.5, 1, 10, 20 and 50μM). 48h later, the cells were incubated with MTT solution (500μg/mL) for 4h at 37°C. The formazan was solubilized with DMSO and relative cell viability was measured at 490nm with a microplate reader. Growth inhibition in response to various concentrations of PD173074 was calculated using GraphPad Prism 7.0. |
Reaction Conditions | 0.5, 1, 10, 20 and 50μM; 48h |
Applications | PD173074 significantly arrested HepG2 and Hep3B cells in G1 phase and inhibited cell proliferation. |
| Animal experiment [3]: | |
Animal models | nude mice |
Preparation Method | H510 (1:1 cell suspension) or H69 cells were implanted into the flank of nude mice. When tumors became measurable, 50mg/kg PD173074/mice or equivalent volume of buffer alone were administered daily for 14 or 28d. In addition, mice received or did not receive two doses of 5mg/kg cisplatin. Tumor volume was monitored using a calliper. Animals were sacrificed when tumor burden reached 15mm in any dimension and survival recorded as a Kaplan-Meier plot. Tissues were formalin fixed and paraffin embedded before staining as indicated in the figure legends. For the endomucin experiments, pictures were acquired using a ×10 objective and analyzed using ImageJ. For activated Caspase 3 and cytokeratin 18 scoring, the number of positive cells in five high-power field views/tumor (five tumors per condition) was determined and results represented as bar graphs. The total number of nuclei per field was determined by manual counting using event flagging in Metamorph. |
Dosage form | 50mg/kg;up to 28 days; goral gavage |
Applications | In the H-510 xenograft, tumor growth was impaired similar to that seen with single-agent cisplatin administration, increasing median survival compared with control sham–treated animals. Crucially, the effect of cisplatin was significantly potentiated by coadministration of PD173074. In H-69 xenografts, PD173074 induced complete responses lasting >6 months in 50% of mice. |
References: | |
Product Documents
Purity:>98.00%Appearance:A solid
Chemical Properties
CAS No.
219580-11-7
Synonyms
PD 173074,PD-173074
Chemical Name
1-tert-butyl-3-[2-[4-(diethylamino)butylamino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea
SMILES
CCN(CC)CCCCNC1=NC2=NC(=C(C=C2C=N1)C3=CC(=CC(=C3)OC)OC)NC(=O)NC(C)(C)C
Molecular Formula
C28H41N7O3
Molecular Weight
523.67
Solubility
≥ 26.1835mg/mL in DMSO, ≥ 108.4 mg/mL in EtOH with ultrasonic
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.
CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility
g/mol
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