For research use only. Not for therapeutic Use.
GSK215 is a potent and selective PROTAC focal adhesion kinase (FAK) degrader with a pDC50 of 8.4. GSK215 is designed by a binder for the VHL E3 ligase and the FAK inhibitor VS-4718. GSK215 induces rapid and prolonged FAK degradation, giving a long-lasting effect on FAK levels and a marked pharmacokinetic/pharmacodynamics (PK/PD) disconnect[1].
GSK215 (0.1-1000 nM; 2 h) effectively increases the FAK degradation by >90% and determines a DC50 of 1.3 nM in A549 cells[1].?
GSK215 induced degradation is proteasome and ubiquitin dependent[1]. ?
GSK215 (above 100 nM, 6h) reduces primarily kinases CDK7, RPS6KA3, MET and GAK[1].?
GSK215 (100 nM, 48 h) inhibits migration, invasion and collagen deposition in A549 cells[1].
GSK215 (8 mg/kg; i.h.; once) degrades FAK, and shows the Cmax and tmax values of 526 ng/mL and 0.33 hours, respectively[1].
| Catalog Number | I045388 |
| CAS Number | 2743427-26-9 |
| Synonyms | (2S,4R)-4-hydroxy-1-[(2S)-2-[[2-[4-[3-methoxy-4-[[4-[2-(methylcarbamoyl)anilino]-5-(trifluoromethyl)pyridin-2-yl]amino]phenyl]piperazin-1-yl]acetyl]amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide |
| Molecular Formula | C50H59F3N10O6S |
| Purity | ≥95% |
| InChI | InChI=1S/C50H59F3N10O6S/c1-29(31-12-14-32(15-13-31)44-30(2)56-28-70-44)57-47(67)40-23-34(64)26-63(40)48(68)45(49(3,4)5)60-43(65)27-61-18-20-62(21-19-61)33-16-17-38(41(22-33)69-7)59-42-24-39(36(25-55-42)50(51,52)53)58-37-11-9-8-10-35(37)46(66)54-6/h8-17,22,24-25,28-29,34,40,45,64H,18-21,23,26-27H2,1-7H3,(H,54,66)(H,57,67)(H,60,65)(H2,55,58,59)/t29-,34+,40-,45+/m0/s1 |
| InChIKey | ZGSWGXNEXAXEGV-XFCHVEHOSA-N |
| SMILES | CC1=C(SC=N1)C2=CC=C(C=C2)C(C)NC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CN4CCN(CC4)C5=CC(=C(C=C5)NC6=NC=C(C(=C6)NC7=CC=CC=C7C(=O)NC)C(F)(F)F)OC)O |
| Reference | [1]. Law RP, Nunes J, Chung CW, et al. Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs [published online ahead of print, 2021 Aug 20]. Angew Chem Int Ed Engl. 2021;10.1002/anie.202109237. |
