TH9619 | TH9619 : Inhibitor of MTHFD1, MTHFD2, MTHFD2L
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 reviews)
Control Compounds
Vendors

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
MTHFD1
  • IC50:16 nM
  • EC50:15-20 nM
MTHFD2
  • IC50:47 nM
  • Kd:8.6 ± 0.4 nM
  • EC50:11 nM
  • ΔTm:5.9 nM
MTHFD2L
  • IC50:47 nM
    Inhibitor
    up to 1 uM

    Selectivity

    In Vitro Selectivity Assessment
    Potency Assay Off-Target:
    DSF-based selectivity screen of TH9619 12 µM against a curated library of 44 kinases, using staurosp ...
    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    no stabilization of mitochondrial MTHFD2 using CETSA on purified subcellular fractions of mitochondr ...

    Potency
    Cellular
    In Vitro

    MTHFD1

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? No

    DOI Reference: 10.1038/s42255-023-00771-5

    MTHFD2

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? No

    DOI Reference: 10.1038/s43018-022-00331-y

    MTHFD2L

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? No

    DOI Reference: 10.1038/s43018-022-00331-y

    In Vivo Validations

    Mouse
    Dose: 10 mg/Kg
    Route of delivery: Subcutaneous
    Plasma half life: 1.68 h
    Cmax: 26.2 uM
    Tmax: 0.25 h
    Area Under the Curve:: 11.2 uM*h

    DOI Reference: 10.1038/s43018-022-00331-y

    Chemical Information

    Molecular Formula C17H18FN7O7
    SMILEs Nc1nc(=O)c(CC(=O)Nc2cnc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c(F)c2)c(N)[nH]1
    InChI InChI=1S/C17H18FN7O7/c18-8-3-6(22-10(26)4-7-13(19)24-17(20)25-14(7)29)5-21-12(8)15(30)23-9(16(31)32)1-2-11(27)28/h3,5,9H,1-2,4H2,(H,22,26)(H,23,30)(H,27,28)(H,31,32)(H5,19,20,24,25,29)/t9-/m0/s1
    Molecular weight 451.13 Da
    AlogP 0.0
    HBond acceptors 14
    HBond donors 9
    Atoms 50

    References

    Cross References

    canSARPDB

    Expert Reviews


    (on 8 Aug 2024 )
    Cellular Use Rating
    In Model Organisms
    TH9619 is a well-characterized double-digit nanomolar inhibitor for MTHFD2, MTHFD2L and MTHFD1. Compared to previously described inhibitors such as LY345899 or DS18561882 it shows significantly improved...
    Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria