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WZ4002 | WZ4002 : Covalent, mutant selective inhibitor of EGFR
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
EGFR (Mutant:WT, T790M, L858R, L858R/T790M)
  • Kd:14 nM
  • Kd:2.2 nM
  • Kd:1.5 nM
  • Kd:0.13 nM
  • IC50:2 nM EGFR-L858R; 8 nM EGFR-L858R/T790M; 3 nM EGFR (del); 2 nM EGFR (del/T790M)
up to 100 nM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
Profiled against a panel of 400 kinases using the Ambit kinome screening platform. wildetype ERBB2 w ...

Potency
Cellular
In Vitro

EGFR (Mutant:WT, T790M, L858R, L858R/T790M)

Mode of Action: Covalent Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1038/nature08622

In Vivo Validations

Mouse
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 1.76 h
Systemic clearance: 17.1 mL/min/Kg
Cmax: 1485 ng/mL
Area Under the Curve:: 976 h.ng/ml
Volume of Distribution at Steady-State: 1.54 L/Kg

DOI Reference: 10.1038/nature08622

Dose: 10 mg/Kg
Route of delivery: Oral
Plasma half life: 2.46 h
Cmax: 429 ng/mL
Tmax: 0.25 h
Area Under the Curve:: 2396 h.ng/ml
Bioavailability: 24.5%

DOI Reference: 10.1038/nature08622

Orthogonal Probes def

ROCILETINIB

Chemical Information

Molecular Formula C25H27ClN6O3
SMILEs C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ncc2Cl)c1
InChI InChI=1S/C25H27ClN6O3/c1-4-23(33)28-17-6-5-7-19(14-17)35-24-20(26)16-27-25(30-24)29-21-9-8-18(15-22(21)34-3)32-12-10-31(2)11-13-32/h4-9,14-16H,1,10-13H2,2-3H3,(H,28,33)(H,27,29,30)
Molecular weight 494.18 Da
AlogP 4.550800000000003
HBond acceptors 9
HBond donors 2
Atoms 62

Vendors

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Expert Reviews

by SERP
(on 2 Mar 2021)
Cellular Use Rating
In Model Organisms
WZ4002 is a covalent inhibitor of EGFR variants carrying the T790M mutant. The cmpd shows roughly a 10fold selectivity window vs. EGFR wt in cellular studies which also translates into in vivo studies....
by SERP
(on 2 Mar 2021)
Cellular Use Rating
In Model Organisms
This is a covalent inhibitor of various EGFR mutants and is potent in biochemical and cellular assays. Depending on the cell line used, the selectivity for EGFR over other cysteine containing kinases,...
by SERP
(on 12 Mar 2021)
Cellular Use Rating
In Model Organisms
WZ4002 is identified as a covalent inhibitor potent against EGFR mutants including both primary activating mutations (e.g., L858R, ΔE746-A750) and resistant mutation T790M (e.g., L858R/T790M, ΔE746-A750/T790M...
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