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DYR684 | DYR684 : Degrader (PROTAC) of DYRK1A and DYRK1B
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 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
DYRK1A
    • Dmax:~90%
    • DC50:12.3 nM
    DYRK1B
      • Dmax:~50%
      • Activity:1 µM
      Degrader (PROTAC)
      100 nM, up to 300 nM

      Selectivity

      In Vitro Selectivity Assessment
      Potency Assay Off-Target:
      KinomeScan of DYR684 at 1 μM reveals that DYR684 targets 11 out of 468 kinases (S(35) score 0.024).
      In Cell Selectivity Assessment
      Potency Assay Off-Target:
      Unbiased quantitative global proteomic profiling was used to assess selectivity in cell. Over 6500 p ...

      Potency
      Cellular
      In Vitro

      DYRK1A

      Mode of Action: Degrader (PROTAC)

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.4c01130

      DYRK1B

      Mode of Action: Degrader (PROTAC)

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.4c01130

      In Vivo Validations

      Mouse
      Dose: 1 mg/Kg
      Route of delivery: Intravenous
      Plasma half life: 3.33 h
      Systemic clearance: 7.1 L/h/Kg
      Area Under the Curve:: 2456 h*ng/mL
      Volume of Distribution at Steady-State: 0.614 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.4c01130

      Dose: 10 mg/Kg
      Route of delivery: Intraperitoneal
      Plasma half life: 4.75 h
      Cmax: 8127 ng/mL
      Tmax: 0.25 h
      Area Under the Curve:: 26303 h*ng/mL
      Bioavailability: 109%

      DOI Reference: 10.1021/acs.jmedchem.4c01130

      Dose: 10 mg/Kg
      Route of delivery: Oral
      Plasma half life: 2.11 h
      Cmax: 18.5 ng/mL
      Tmax: 0.5 h
      Area Under the Curve:: 56 h*ng/mL
      Bioavailability: 0.25%

      DOI Reference: 10.1021/acs.jmedchem.4c01130

      Negative Control Compounds

      canSAR7437539
      Notes: DYR813 as an inactive control that is unable to bind CRBN

      Chemical Information

      Molecular Formula C58H58FN15O5
      SMILEs Cc1nc2ccc(-c3ccnc(N)c3)nc2n1-c1ccc(N2CCN(CC#Cc3ccc(N4CCC(C(=O)N5CCC(n6cc(CNc7cccc8c7C(=O)N(C7CCC(=O)NC7=O)C8=O)cn6)CC5)CC4)nc3)CC2)c(F)c1
      InChI InChI=1S/C58H58FN15O5/c1-36-65-47-10-9-45(40-15-20-61-50(60)30-40)66-54(47)73(36)42-8-11-48(44(59)31-42)69-28-26-68(27-29-69)21-3-4-37-7-13-51(63-32-37)70-22-16-39(17-23-70)56(77)71-24-18-41(19-25-71)72-35-38(34-64-72)33-62-46-6-2-5-43-53(46)58(79)74(57(43)78)49-12-14-52(75)67-55(49)76/h2,5-11,13,15,20,30-32,34-35,39,41,49,62H,12,14,16-19,21-29,33H2,1H3,(H2,60,61)(H,67,75,76)
      Molecular weight 1063.47 Da
      AlogP 5.370820000000004
      HBond acceptors 20
      HBond donors 4
      Atoms 137
      PAINS * Yes

      * This is an automated alert only, and may not necessarily indicate an issue with this probe. ( Learn more about PAINS )

      References

      Publications

      Cross References

      Vendors

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      Expert Reviews

      by SERP
      (on 25 Oct 2024 )
      Cellular Use Rating
      In Model Organisms
      DYR684 is a very well characterized degrader of DYRK1A and DYRK1B. It is a very good probe for cellular studies as it can be used at moderate nanomolar concentrations and showed good selectivity in an...
      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