PD173074

Catalog No.S1264 Batch:S126403

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Technical Data

Formula

C28H41N7O3
Molecular Weight 523.67 CAS No. 219580-11-7
Solubility (25°C)* In vitro DMSO 105 mg/mL (200.5 mM)
Ethanol 105 mg/mL (200.5 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description PD173074 is a potent FGFR1 inhibitor with IC50 of ~25 nM and also inhibits VEGFR2 with IC50 of 100-200 nM in cell-free assays, ~1000-fold selective for FGFR1 than PDGFR and c-Src. PD173074 reduces proliferation and promotes apoptosis in gastric cancer cells.
Targets
FGFR1 [1]
(Cell-free assay)		 VEGFR2 [1]
(Cell-free assay)
~25 nM 100 nM-200 nM
In vitro PD173074 is an ATP-competitive inhibitor of FGFR1 with Ki of ~40 nM. PD173074 is also an effective inhibitor of VEGFR2. Compared to FGFR1, PD173074 weakly inhibits the activities of Src, InsR, EGFR, PDGFR, MEK, and PKC with 1000-fold or greater IC50 values. PD173074 inhibits autophosphorylation of FGFR1 and VEGFR2 in a dose-dependent manner with IC50 of 1-5 nM and 100-200 nM, respectively. [1] PD173074 inhibits FGF-2 promotion of granule neuron survival in a dose-dependent manner with IC50 of 12 nM, exhibiting 1,000-fold greater potency than that of SU 5402. [2] PD173074 specifically inhibits FGF-2-mediated effects on proliferation, differentiation, and MAPK activation in oligodendrocyte (OL) lineage cells. [3] PD173074 is active against the WT receptor and FGFR3 mutations in multiple myeloma (MM) cell lines. PD173074 also potently inhibits autophosphorylation of FGFR3 in a dose-dependent manner with IC50 of ~5 nM. PD173074 treatment potently reduces viability of FGFR3-expressing KMS11 and KMS18 cells with IC50 of <20 nM. Inhibition of aFGF-stimulated MM cell growth by PD173074 is highly correlated with the expression of FGFR3. PD173074 treatment completely abolishes NIH 3T3 transformation mediated by Y373C FGFR3 but not by Ras V12, demonstrating that PD173074 specifically targets FGFR3-mediated cell transformation and lacks nonspecific cytotoxic effect. PD173074 also induces functional maturation of KMS11 and KMS18 cells. [4]
In vivo Administration of PD173074 at 1 mg/kg/day or 2 mg/ka/day in mice can effectively block angiogenesis induced by either FGF or VEGF in a dose-dependent manner with no apparent toxicity. [1] PD173074 inhibits in vivo growth of mutant FGFR3-transfected NIH 3T3 cells in nude mice. Inhibition of FGFR3 by PD173074 delays tumor growth and increases survival of mice in a KMS11 xenograft myeloma model. [4] In the H-510 xenograft, oral aministration of PD173074 blocks tumor growth similar to that seen with single-agent cisplatin administration, increasing median survival compared with control sham-treated animals. In H-69 xenografts, PD173074 induces complete responses lasting >6 months in 50% of mice. These effects are correlated with increased apoptosis in excised tumors, but not a consequence of disrupted tumor vasculature. [5]

Protocol (from reference)

Kinase Assay:[1]
  • In vitro kinase inhibition assays

    Assays using the full-length FGFR-1 kinase are performed in a total volume of 100 μL containing 25 mM HEPES buffer (pH 7.4), 150 mM NaCl, 10 mM MnCl2, 0.2 mM sodium orthovanadate, 750 μg/mL concentration of a random copolymer of glutamic acid and tyrosine (4:1), various concentrations of PD173074 and 60 to 75 ng of enzyme. The reaction is initiated by the addition of [γ-32P]ATP (5 μM ATP containing 0.4 μCi of [γ-32P]ATP per incubation), and samples are incubated at 25°C for 10 minutes. The reaction is terminated by the addition of 30% trichloroacetic acid and the precipitation of material onto glass-fiber filter mats. Filters are washed three times with 15% trichloroacetic acid, and the incorporation of [32P] into the glutamate tyrosine polymer substrate is determined by counting the radioactivity retained on the filters in a Wallac 1250 betaplate reader. Nonspecific activity is defined as radioactivity retained on the filters following incubation of samples without enzyme. Specific activity is determined as total activity (enzyme plus buffer) minus nonspecific activity. The concentration of PD173074 that inhibits FGFR-1 enzymatic activity by 50% (IC50) is determined graphically.
Cell Assay:[4]
  • Cell lines

    KMS11 and KMS18

  • Concentrations

    Dissolved in DMSO, final concentrations ~100 nM

  • Incubation Time

    48 hours

  • Method

    Cells are incubated with increasing concentrations of PD173074 in the presence of aFGF/heparin for 48 hours. The percentage of viable cells is determined by MTT.
Animal Study:[1]
  • Animal Models

    Swiss Webster mice with induced corneal angiogenesis

  • Dosages

    ~2 mg/kg/day

  • Administration

    Administered intraperitoneally

Customer Product Validation

Data from [Data independently produced by Hepatology, 2014, 59(4) ,1427-34]

Data from [Data independently produced by J Cell Sci, 2014, 10.1242/jcs.159608]

Data from [Data independently produced by Cancer Discov, 2013, 3(6), 636-47]

Data from [Data independently produced by PLoS Genet, 2012, 8(2), e1002500]

Selleck's PD173074 has been cited by 118 publications

Smad4 is essential for epiblast scaling and morphogenesis after implantation, but nonessential prior to implantation in the mouse [ bioRxiv, 2024, 2024.01.23.576717] PubMed: 38328075
FGF21 increases the sensitivity of sorafenib to hepatocellular carcinoma under hypoxia [ Malignancy Spectrum, 2024, 10.1002/msp2.20] PubMed: none
Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice [ JCI Insight, 2023, 8(10)e154729] PubMed: 37079375
Genome-wide open reading frame profiling identifies fibroblast growth factor signaling as a driver of PD-L1 expression in head and neck squamous cell carcinoma [ Oral Oncol, 2023, 146:106562] PubMed: 37666053
Unraveling the Mechanisms of Sensitivity to Anti-FGF Therapies in Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Lacking Secondary KIT Mutations [ Cancers (Basel), 2023, 15(22)5354] PubMed: 38001614
Pregranulosa cell-derived FGF23 protects oocytes from premature apoptosis during primordial follicle formation by inhibiting p38 MAPK in mice [ J Biol Chem, 2023, 299(6):104776] PubMed: 37142227
FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathway [ Brain Res Bull, 2023, 202:110753] PubMed: 37660729
Comparison of Four Protocols for In Vitro Differentiation of Human Embryonic Stem Cells into Trophoblast Lineages by BMP4 and Dual Inhibition of Activin/Nodal and FGF2 Signaling [ Reprod Sci, 2023, 10.1007/s43032-023-01334-5] PubMed: 37658178
FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells [ Mil Med Res, 2022, 9(1):7] PubMed: 35093168
Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival [ Nat Commun, 2022, 13(1):6589] PubMed: 36329028

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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