For research use only. Not for therapeutic Use.
FMK is a an irreversible RSK2 kinase inhibitor, that covalently modifies the C-terminal kinase domain of RSK.
Pretreatment of ARVMs with 3 μM fmk attenuates the increase in Ser386 phosphorylation, but it has no inhibitory effect on the increase in Thr577 phosphorylation[1]. FMK inhibits relatively few protein kinases in the panel, although it does inhibit protein tyrosine kinases, such as Src, Lck, Yes and Eph-A2, as well as S6K1. FMK will not inhibit RSK if the N-terminal kinase domain are activated by a mechanism that is independent of the C-terminal domain[2]. Fmk potently inactivates the CTD auto-kinase activity of RSK1 and RSK2 with high specificity in mammalian cells. Targeting RSK2 by a specific small molecule RSK inhibitor fmk attenuates FGFR3-induced cytokine-independent growth in Ba/F3 cells. FMK inhibits cytokine-independent proliferation of Ba/F3 cells conferred by FGFR3[3].
| Catalog Number | I004975 |
| CAS Number | 821794-92-7 |
| Synonyms | 1-[4-amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-6-yl]-2-fluoroethanone |
| Molecular Formula | C18H19FN4O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C18H19FN4O2/c1-11-3-5-12(6-4-11)14-15-17(20)21-10-22-18(15)23(7-2-8-24)16(14)13(25)9-19/h3-6,10,24H,2,7-9H2,1H3,(H2,20,21,22) |
| InChIKey | IKLGYJACVCXYIL-UHFFFAOYSA-N |
| SMILES | CC1=CC=C(C=C1)C2=C(N(C3=NC=NC(=C23)N)CCCO)C(=O)CF |
| Reference | [1]. Cuello F, et al. Evidence for direct regulation of myocardial Na+/H+ exchanger isoform 1 phosphorylation and activity by 90-kDa ribosomal S6 kinase (RSK): effects of the novel and specific RSK inhibitor fmk on responses to alpha1-adrenergic stimulation. [2]. Bain J, et al. The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315. [3]. Kang S, et al. FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway. Cancer Cell. 2007 Sep;12(3):187-9. |
