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PF-06263276 | PF-06263276 : Inhibitor of JAK1, JAK2, JAK3, TYK2
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
JAK1
  • IC50:2.2 nM
  • IC50:70.3 nM
  • IC50:620 nM
  • IC50:1800 nM
  • IC50:2100 nM
JAK2
  • IC50:23.1 nM
  • IC50:4200 nM
  • IC50:5200 nM
JAK3
  • IC50:59.9 nM
    TYK2
    • IC50:29.7 nM
      Inhibitor
      no higher than 300 nM
      up to 10 uM

      Selectivity

      In Vitro Selectivity Assessment
      Potency Assay Off-Target:
      Profiling PF-06263276 against a panel of 36 kinases at 1 μM demonstrated that it has suitable select ...

      Potency
      Cellular
      In Vitro

      JAK1

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.6b01634

      JAK2

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.6b01634

      JAK3

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.6b01634

      TYK2

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.6b01634

      In Vivo Validations

      Rat
      Dose: 0.5 mg/kg
      Route of delivery: Intravenous
      Plasma half life: 2.1 h
      Systemic clearance: 48 mL/min/Kg
      Volume of Distribution at Steady-State: 0.8 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.6b01634

      Dose: 1 mg/Kg
      Route of delivery: Oral
      Bioavailability: <5%

      DOI Reference: 10.1021/acs.jmedchem.6b01634

      Dog
      Dose: 0.1 mg/Kg
      Route of delivery: Intravenous
      Plasma half life: 2.0 h
      Systemic clearance: 18 mL/min/Kg
      Volume of Distribution at Steady-State: 1.0 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.6b01634

      Chemical Information

      Molecular Formula C31H31FN8O2
      SMILEs CCc1cc(O)c(F)cc1-c1ccc2c(-c3nc4c([nH]3)CCN(C(=O)c3cnc(N5CCCCC5)cn3)C4)n[nH]c2c1
      InChI InChI=1S/C31H31FN8O2/c1-2-18-13-27(41)22(32)14-21(18)19-6-7-20-24(12-19)37-38-29(20)30-35-23-8-11-40(17-26(23)36-30)31(42)25-15-34-28(16-33-25)39-9-4-3-5-10-39/h6-7,12-16,41H,2-5,8-11,17H2,1H3,(H,35,36)(H,37,38)
      Molecular weight 566.26 Da
      AlogP 5.0059
      HBond acceptors 10
      HBond donors 3
      Atoms 73

      References

      Publications

      Cross References

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      Expert Reviews

      by SERP
      (on 18 Jun 2023 )
      Cellular Use Rating
      In Model Organisms
      I would recommend caution in using higher concentrations of this compound in cells. Although the recommendations line up with the IC50s reported in Jones et al., this compound is a very potent kinase inhibitor,...
      by SERP
      (on 19 Jun 2023 )
      Cellular Use Rating
      In Model Organisms
      While PF-06263276 clearly is a 'quality' molecule from Pfizer, it was specifically designed for inhaled delivery and properties were optimized for this route of administration (incl. e.g. high clearance!)...
      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