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()
    MSC2530818
    MSC2530818

    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 #: V2742
    CAS #: 1883423-59-3Purity ≥98%

    Description: MSC2530818 is novel,  potent, selective and orally available small molecule inhibitor of cyclin dependent kinase CDK8 with the IC50 of 2.6 nM. It demonstrates excellent pharmacokinetics and pharmacodynamics including good kinase selectivity, high biochemical and cellular potency, microsomal stability, and reasonable oral bioavailability. The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development of colorectal cancer. MSC2530818 was identified in a high-throughput screening campaign and further progressed by structure-based design. MSC2530818 demonstrated suitable potency and selectivity to progress into preclinical in vivo efficacy and safety studies.

    References:  2016 Oct 27;59(20):9337-9349. 


    Customer Validation
    Official Supplier of
    • VE
    • OF
    • YALE
    • hhmi
    • 香港大学
    Related Products
    Publications Citing InvivoChem Products
    • Physicochemical and Storage Information
    • Protocol
    • Quality Control Documentation
    • Related Biological Data
    • Customer Review
    Molecular Weight (MW) 340.81
    Formula C18H17ClN4O
    CAS No. 1883423-59-3
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: > 70 mg/mL
    Water: <1 mg/mL
    Ethanol: > 70 mg/mL
    Chemical Name [(2S)-2-(4-Chlorophenyl)pyrrolidin-1-yl]-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)methanone
    Synonyms MSC-2530818; MSC2530818; MSC 2530818
    SMILES Code O=C(N1[[email protected]H](C2=CC=C(Cl)C=C2)CCC1)C3=CN=C(NN=C4C)C4=C3


    • 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: MSC2530818 is novel,  potent, selective and orally available small molecule inhibitor of cyclin dependent kinase CDK8 with the IC50 of 2.6 nM. It demonstrates excellent pharmacokinetics and pharmacodynamics including good kinase selectivity, high biochemical and cellular potency, microsomal stability, and reasonable oral bioavailability. The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development of colorectal cancer. MSC2530818 was identified in a high-throughput screening campaign and further progressed by structure-based design. MSC2530818 demonstrated suitable potency and selectivity to progress into preclinical in vivo efficacy and safety studies.


    Kinase Assay: MSC2530818 is novel,  potent, selective and orally available small molecule inhibitor of cyclin dependent kinase CDK8 with the IC50 of 2.6 nM.


    Cell Assay: SC2530818 demonstrates potent inhibition of WNT-dependent transcription in human cancer cell lines that have constitutively activated WNT signaling. For example, MSC2530818 inhibits the reporter-based luciferase readout in several cell lines bearing activating WNT-pathway mutations; LS174T (β-catenin mutant, IC50=32±7 nM), COLO205 (APC mutant, IC50=9±1 nM) and demonstrates inhibition of WNT3a ligand-dependent reporter readout in PA-1 cells (IC50=52±30 nM). MSC2530818 demonstrates minimal activity in the CEREP panel, being active on the dopamine transporter (IC50=8.5 μM) as the only activity below 10 μM, and demonstrates minimal hERG inhibition. Furthermore, MSC2530818 is a soluble CDK8 inhibitor with high permeability and low efflux ratio in Caco-2 cells and does not inhibit any cytochrome P450 subtypes.

    In VivoTumor-bearing mice treated with MSC2530818 shows reduction in tumor growth with T/C ratios (based on final tumor weights) of 49% and 57%, respectively. MSC2530818 is generally well tolerated, with no effects on mouse body weight in the qd administration schedule and manageable body weight loss. The human clearance and volume of distribution at steady-state are estimated to be low (0.14 L/h/kg) and small (0.48 L/kg), respectively, resulting in a short predicted terminal half-life (2.4 h). Physiologically based pharmacokinetics simulations suggested that human oral bioavailability may be ≥75% up to dose level of 500 mg daily
    Animal modelNCr athymic mice
    Formulation & DosagePrepared in  kolliphor 20% w/v in water; 50 mg/kg bid or 100 mg/kg qd; oral gavage 
    References  2016 Oct 27;59(20):9337-9349. 


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

     MSC2530818


    MSC2530818

    Figure 1. (A) Crystal structure of CDK8/cyclin C complexed with compound 6(blue).   2016 Oct 27;59(20):9337-9349.

     


    MSC2530818

    Figure 5. (A) Crystal structure of 25 (violet) complexed with CDK8-cyclin C. (B) Superposition of the 25 (violet) and 6 (blue) crystal structures.

    MSC2530818

    Efficacy study of compound 25 (MSC2530818) in SW620 human colorectal cancer xenografts.  2016 Oct 27;59(20):9337-9349.

     MSC2530818


    Figure 2. (A) SZMAP and WaterMap calculations have been performed for the crystal structure of compound 6 complexed to CDK8/cyclin C.  2016 Oct 27;59(20):9337-9349.

     


    MSC2530818

    Figure 3. (A) Selectivity grids for the CDK8-specific regions of the active site.  2016 Oct 27;59(20):9337-9349.

     MSC2530818


    Figure 4. (A) Crystal structure of 17 (orange) in complex CDK8/cyclin C.  2016 Oct 27;59(20):9337-9349.



    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
      Subscribe to our E-newsletter
      • Name*
      • *
      • E-mail*
      • *
      • instructions:
      • *
      Copyright 2020 InvivoChem LLC | All Rights Reserved
      prompt
      Do you confirm the receipt?