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PROTAC FAK degrader 1 | Degrader (PROTAC) of PTK2
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (0 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
PTK2
  • IC50:6.5 ± 0.5 nM
  • DC50:3.0 ± 1.5 nM
  • Inhibition:93%
Degrader (PROTAC)
up to 100 nM, 'hook effect' observed at 5 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
DiscoverX KINOMEscan was performed for PROTAC-3 at 1 μM. Out of a panel of 403 different kinases PRO ...
Selectivity Assessment Description:
FAK is the only kinase bound by PROTAC-3 with less than 1% of control remaining.
In Cell Selectivity Assessment
Potency Assay Off-Target:
Reverse Phase Protein array (RPPA) analysis was performed to assess proteins levels after treatment ...
Selectivity Assessment Description:
RPPA data from MDA-MB-231 cell lysates indicate a reduced level for AR, p-Akt(S473) and p-Src(Y527). ...

Potency
Cellular
In Vitro

PTK2

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/jacs.8b08008

Negative Control Compounds

PROTAC-7
Notes: Diastereomer PROTAC-7 (IC50 = 11.2 nM) results in a minimal loss of potency compared to its PROTAC-3 (IC50 = 6.5 nM) while not being able to degrade the target in cell.
SMILES: Cc1c(c2ccc(CNC([C@H]3C[C@H](CN3C([C@H](C(C)(C)C)NC(CCOCCOc4ccc(Nc5nc(NCc6cc(N(S(C)(=O)=O)C)ccc6)c(C(F)(F)F)cn5)cc4)=O)=O)O)=O)cc2)scn1

Chemical Information

Molecular Formula C47H56F3N9O8S2
SMILEs Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCOCCOc2ccc(Nc3ncc(C(F)(F)F)c(NCc4cccc(N(C)S(C)(=O)=O)c4)n3)cc2)C(C)(C)C)cc1
InChI InChI=1S/C47H56F3N9O8S2/c1-29-40(68-28-54-29)32-12-10-30(11-13-32)24-52-43(62)38-23-35(60)27-59(38)44(63)41(46(2,3)4)56-39(61)18-19-66-20-21-67-36-16-14-33(15-17-36)55-45-53-26-37(47(48,49)50)42(57-45)51-25-31-8-7-9-34(22-31)58(5)69(6,64)65/h7-17,22,26,28,35,38,41,60H,18-21,23-25,27H2,1-6H3,(H,52,62)(H,56,61)(H2,51,53,55,57)/t35-,38+,41-/m1/s1
Molecular weight 995.36 Da
AlogP 6.273420000000005
HBond acceptors 17
HBond donors 5
Atoms 125

References

Publications

Cross References

canSARChEMBLBindingDB

Expert Reviews

by SERP
(on 24 Jan 2025 )
Cellular Use Rating
( The reviewer did not leave any comments )
by SERP
(on 2 Feb 2025 )
Cellular Use Rating
It is also worth considering the use of GSK215, as this FAK-targeted PROTAC has been found to exhibit potent FAK degradation activity even in mice following a subcutaneous injection. See: Law RP, Nunes...
by SERP
(on 13 Feb 2025 )
Cellular Use Rating
First FAK degrader with very good in-vitro potency and rate of degradation with a Dmax >99%. The compound potently inhibited FAK downstream signaling, such as Axilin and Akt phosphorylation, and was effective...
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