My cart
In the shopping cart is not goods, to choose and buy!
  • Product Name
  • Size
  • Quantity
  • Amount
    Selected items : 0 pieces Total : CHECK OUT()
    PF-3758309
    PF-3758309

    Price:
    Market Price:

    This product is for research use only, not for human use. We do not sell to patients.
    Number: - + Pieces(InventoryPieces)
    InvivoChem Cat #: V1594
    CAS #: 898044-15-0Purity ≥98%

    Description: PF-03758309, a pyrrolopyrazole analog, is a novel, potent, orally bioavailable, and ATP-competitive small molecule inhibitor of PAK4 (p21-activated kinase 4) with IC50 of 1.3 NM. As an inhibitor of PAK4,PF-3758309  has potential antineoplastic activity.  PF-03758309 binds to PAK4 and inhibits PAK4 activity and cancer cell growth. PAK4, a serine/threonine kinase belonging to the p21-activated kinase (PAK) family, is often upregulated in a variety of cancer cell types and plays an important role in cancer cell motility, proliferation, and survival. 

    References: Proc Natl Acad Sci U S A. 2010 May 18;107(20):9446-51.

    Customer Validation
    Official Supplier of
    • VE
    • OF
    • YALE
    • hhmi
    • 香港大学
    Related Products
    Publications Citing InvivoChem Products
    • Citation of InvivoChem venetoclax and S63845
    • Citation of InvivoChem KD025 (SLx-2119)
    • Citation of InvivoChem Tubastatin A HCl
    • Citation of InvivoChem Paclitaxel
    • Citation of InvivoChem Colchicine
    • Citation of InvivoChem CA-170
    • Physicochemical and Storage Information
    • Protocol
    • Quality Control Documentation
    • Related Biological Data
    • Customer Review
    Molecular Weight (MW)490.62
    FormulaC25H30N8OS
    CAS No.898044-15-0
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 98 mg/mL (199.7 mM)
    Water: <1 mg/mL
    Ethanol: 98 mg/mL (199.7 mM)
    Other infoChemical Name: (S)-N-(2-(dimethylamino)-1-phenylethyl)-6,6-dimethyl-3-((2-methylthieno[3,2-d]pyrimidin-4-yl)amino)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide.
    InChi Key: AYCPARAPKDAOEN-LJQANCHMSA-N
    InChi Code: InChI=1S/C25H30N8OS/c1-15-26-18-11-12-35-20(18)23(27-15)29-22-17-13-33(25(2,3)21(17)30-31-22)24(34)28-19(14-32(4)5)16-9-7-6-8-10-16/h6-12,19H,13-14H2,1-5H3,(H,28,34)(H2,26,27,29,30,31)/t19-/m1/s1
    SMILES Code: O=C(N(C1)C(C)(C)C2=C1C(NC3=C4C(C=CS4)=NC(C)=N3)=NN2)N[C@@H](C5=CC=CC=C5)CN(C)C
    SynonymsPF-03758309; PF03758309; PF 03758309; PF-3758309; PF-3758309; PF3758309; PF 3758309.


    • Molarity Calculator
    • Dilution Calculator
    • The molarity calculator equation

      Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

      • Mass
      • Concentration
      • Volume
      • Molecular Weight *
      • =
      • ×
      • ×
    • The dilution calculator equation

      Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

      This equation is commonly abbreviated as: C1V1 = C2V2

      • Concentration (start)
      • ×
      • Volume (start)
      • =
      • Concentration (final)
      • ×
      • Volume (final)
      • ×
      • =
      • ×
      • C1
      •  
      • V1
      •  
      • C2
      •  
      • V2
    In Vitro

    In vitro activity: PF-3758309 is a potent (Kd = 2.7 nM), ATP-competitive inhibitor of PAK4 with Ki of 18.7 nM. In cells, PF-3758309 inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC50 = 1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC50 = 4.7 nM). PF-3758309 also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. PF-3758309 potently inhibits cellular proliferation (IC50 = 20 nM) and anchorage-independent growth (IC50 = 27 nM) of A549 cells.


    Kinase Assay: TR-293-KDG cells are constructed from HEK293 cells stably transfected with tetracycline-inducible PAK4-kinase domain (amino acids 291-591) and constitutively expressed HA-tagged GEFH1ΔDH (amino acids 210-921). TR-293-KDG cells are incubated for 3 h with PF-3758309, captured on an anti-HA antibody-coated plate, detected with an anti-phospho-S810-GEF-H1 antibody, and quantified with a horseradish peroxidase-goat anti-rabbit antibody conjugate.


    Cell Assay: A panel of cancer cell lines is used to test the potency of PF-3758309. On day 1, cells are plated on 384-well plates. Onday2, compounds are added to the cell culture. The cells are incubated with the compound for 3 days. On day 5, all media are aspirated from the wells. Dose-dependent effects of PF-3758309 on cell proliferation are quantified via the CellTiter-Glo Luminescent Cell Viability Assay(a,b,c), which is a homogeneous method of determining the number of viable cells in culture based on quantitation of the ATP present, an indicator of metabolically active cells. Proliferation data displayed for HEK293T, HCT116, and SKOV3 cells are measured using the Cyquant NF assay as specified by the manufacturer. Briefly, 24 h after seeding on 384-well plates, cells are treated with vehicle or PF-3758309, Dasatinib, or the positive control, Bleomycin (60 mU/ mL).72 hours after drug treatment, cell proliferation is measured. Results for each drug are normalized to vehicle control and expressed as a percentage of maximum assay inhibition relative to Bleomycin. Error bars represent the SD from at least three experiments.

    In VivoPF-3758309 blocks the growth of multiple human tumor xenografts, with a plasma EC50 value of 0.4 nM in the most sensitive model. PF-3758309 is antiproliferative and induces apoptosis in a HCT116 tumor model.  
    Animal modelXenograft tumors in nude mice 
    Formulation & DosageDissolved in 0.5% methylcellulose; 7.5-30 mg/kg BID; p.o. administration 
    References

    Proc Natl Acad Sci U S A. 2010 May 18;107(20):9446-51.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    PF-3758309
    PF-3758309 has a unique profile of cellular activity. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9446-51.

    PF-3758309

    PF-3758309 is antiproliferative and induces apoptosis in a HCT116 tumor model. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9446-51.

    PF-3758309

    Structural characterization of PF-3758309 binding to the PAK4 catalytic domain. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9446-51.

     

    PF-3758309

    Tumor growth inhibition of human xenograft tumor models.

    PF-3758309

    PF-3758309 is antiproliferative and induces apoptosis in a HCT116 tumor model. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9446-51.


    评论

      Home Prev Next Last page / pices

      发评论

      ×
      Your information is safe with us. * Required Fields.
      Products are for research use only;  We do not sell to patients
      Tel: 1-708-310-1919
      Fax: 1-708-557-7486
      Email: sales@invivochem.com
      Subscribe to our E-newsletter
      • Name*
      • *
      • E-mail*
      • *
      • instructions:
      • *
      Copyright 2020 InvivoChem LLC | All Rights Reserved