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Entospletinib | Inhibitor of SYK
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

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Targets Biochemical/Biophysical Potency Cellular Potency
SYK
  • IC50:7.7 nM
  • EC50:26 nM
  • EC50:41 ± 27 nM
Inhibitor
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
Profiled using the KinomeScan platform against a panel of 359 nonmutant kinases at a single conce ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
target protein phosphorylation assay
Selectivity Assessment Description:
In cells, Entospletinib inhibited Flt3, Jak2, c-Kit, KDR, and Ret with 13- to >1000-fold cellu ...

Potency
Cellular
In Vitro

SYK

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/jm500228a

In Vivo Validations

Rat
Dose: 0.4 mg/Kg (IV), 1.0 (PO) mg/Kg
Route of delivery: Intravenous, Oral
Plasma half life: 35 min
Systemic clearance: 0.27 L/h/kg IV
Fb : 99.2%
Bioavailability: 67 ± 9% PO
Volume of Distribution at Steady-State: 0.52 ± 0.05 L/Kg IV

DOI Reference: 10.1021/jm500228a

Dog
Dose: 0.4 mg/Kg IV, 1.0 mg/Kg PO
Route of delivery: Intravenous, Oral
Systemic clearance: 0.80 ± 0.03 L/h/Kg IV
Fb : 92.8%
Bioavailability: 53 ± 16% PO
Volume of Distribution at Steady-State: 1.41 ± 0.40 L/Kg IV

DOI Reference: 10.1021/jm500228a

Orthogonal Probes def

PRT062607

Chemical Information

Molecular Formula C23H21N7O
SMILEs c1cn2cc(-c3ccc4cn[nH]c4c3)nc(Nc3ccc(N4CCOCC4)cc3)c2n1
InChI InChI=1S/C23H21N7O/c1-2-17-14-25-28-20(17)13-16(1)21-15-30-8-7-24-23(30)22(27-21)26-18-3-5-19(6-4-18)29-9-11-31-12-10-29/h1-8,13-15H,9-12H2,(H,25,28)(H,26,27)
Molecular weight 411.18 Da
AlogP 3.852800000000002
HBond acceptors 8
HBond donors 2
Atoms 52
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

ChEMBL BindingDB PDB PubChem DrugBank canSAR

Vendors

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Expert Reviews

by SERP
(on 1 Aug 2021)
Cellular Use Rating
In Model Organisms
Although quite selective, it is important to note that cellular effects of Jak2, ckit, and Flt3 inhibition are seen at EC50 values of 330-450 nM. If these kinases may be relevant to the pathway of interest,...
by SERP
(on 6 Aug 2021)
Cellular Use Rating
In Model Organisms
Entospletinib required formulation in NMP/PEG-400 to determine its PK in CD1 mice due to its poor solubility. This solubility needs to be improved to improve its utility in vivo.
by SERP
(on 12 Sept 2021)
Cellular Use Rating
In Model Organisms
Reviewer recommended dose in vivo: use both 1 mg/mL and 3 mg/mL dosing regimen for in vivo studies as higher dose resulted in at least 50% target coverage (pSyk EC50).
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