GNE-2256 | Inhibitor of IRAK4
RATINGS:
Cellular Use: (0 reviews)

In Model Organisms: (0 reviews)

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
IRAK4
  • Ki:1.4 ±0.32 nM
  • Inhibition:80 ± 9.2 %
  • IC50:190 ± 79 nM
  • IC50:3.3 nM
  • IC50:290 nM
Inhibitor
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
Selectivity within target family - Kinase panel (221) at 1 µM: Closest off-targets (IC50 [nM]) are F ...

Potency
Cellular
In Vitro

IRAK4

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acsmedchemlett.9b00380

In Vivo Validations

Mouse
Dose: 1 mg/Kg IV and PO
Route of delivery: Intravenous, Oral
Plasma half life: 1.9 h
Systemic clearance: 29 mL/min/kg
Area Under the Curve:: 1.2 μM·h
Fb : 94.2%
Bioavailability: 34%
Volume of Distribution at Steady-State: 2.2 L/Kg

DOI Reference: 10.1021/acsmedchemlett.9b00380

Rat
Dose: 1 mg/Kg IV and PO
Route of delivery: Intravenous, Oral
Plasma half life: 1.6 h
Systemic clearance: 9.2 mL/min/Kg
Area Under the Curve:: 3.8 μM·h
Fb : 91.4%
Bioavailability: 31%
Volume of Distribution at Steady-State: 0.95 L/Kg

DOI Reference: 10.1021/acsmedchemlett.9b00380

Dog
Dose: 1 mg/Kg IV and PO
Route of delivery: Intravenous, Oral
Plasma half life: 4.1 h
Systemic clearance: 11.3 mL/min/Kg
Area Under the Curve:: 3.1 μM·h
Fb : 77.6 %
Bioavailability: 109%
Volume of Distribution at Steady-State: 3.7 L/Kg

DOI Reference: 10.1021/acsmedchemlett.9b00380

Monkey (Cynomolgus)
Dose: 1 mg/Kg IV and PO
Route of delivery: Intravenous, Oral
Plasma half life: 5.4 h
Systemic clearance: 15.8 mL/min/Kg
Area Under the Curve:: 2.2 μM·h
Fb : 66.8%
Bioavailability: 47%
Volume of Distribution at Steady-State: 3.7 L/Kg

DOI Reference: 10.1021/acsmedchemlett.9b00380

Negative Control Compounds

GNE-6689
Notes: GNE-6689: NanoBRET: IC50 = 7.26 µM (SGC Frankfurt) Clean kinase profile, clean CEREP panel
InChI: InChI=1S/C25H29FN6O4/c1-25(2,35)21(26)15-31-14-16-11-19(20(12-17(16)24(31)34)30-7-9-36-10-8-30)29(3)23(33)18-13-28-32-6-4-5-27-22(18)32/h4-6,11-13,21,35H,7-10,14-15H2,1-3H3/t21-/m1/s1

Chemical Information

Molecular Formula C24H27FN6O4
SMILEs CC(C)(O)[C@H](F)CN1Cc2cc(NC(=O)c3cnn4cccnc34)c(N3CCOCC3)cc2C1=O
InChI InChI=1S/C24H27FN6O4/c1-24(2,34)20(25)14-30-13-15-10-18(19(11-16(15)23(30)33)29-6-8-35-9-7-29)28-22(32)17-12-27-31-5-3-4-26-21(17)31/h3-5,10-12,20,34H,6-9,13-14H2,1-2H3,(H,28,32)/t20-/m1/s1
Molecular weight 482.21 Da
AlogP 1.883
HBond acceptors 10
HBond donors 2
Atoms 62
PAINS * Yes

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

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Expert Reviews


No SERP comments found for GNE-2256

Probe GNE-2256 is in the process of SERP review.

Please continue to check back for new reviews and commentary.