SRPIN340(Cat No.:I002667)is a selective inhibitor of serine-arginine protein kinases (SRPKs), particularly SRPK1, which plays a key role in RNA splicing regulation by phosphorylating splicing factors. By inhibiting SRPK1, SRPIN340 interferes with the alternative splicing of pre-mRNA, affecting the expression of proteins involved in various cellular processes, including cancer progression and viral replication. SRPIN340 has shown potential in research targeting cancer and viral infections, such as hepatitis C, where splicing regulation is crucial. Its specificity for SRPK1 makes it a valuable tool for studying splicing mechanisms and therapeutic development.
Catalog Number | I002667 |
CAS Number | 218156-96-8 |
Synonyms | N-[2-piperidin-1-yl-5-(trifluoromethyl)phenyl]pyridine-4-carboxamide |
Molecular Formula | C18H18F3N3O |
Purity | ≥95% |
Target | SRPK |
Solubility | DMSO: ≥ 42 mg/mL |
Storage | Store at -20C |
IC50 | 0.89 uM (SRPK1) |
IUPAC Name | N-[2-piperidin-1-yl-5-(trifluoromethyl)phenyl]pyridine-4-carboxamide |
InChI | InChI=1S/C18H18F3N3O/c19-18(20,21)14-4-5-16(24-10-2-1-3-11-24)15(12-14)23-17(25)13-6-8-22-9-7-13/h4-9,12H,1-3,10-11H2,(H,23,25) |
InChIKey | DWFGGOFPIISJIT-UHFFFAOYSA-N |
SMILES | C1CCN(CC1)C2=C(C=C(C=C2)C(F)(F)F)NC(=O)C3=CC=NC=C3 |
Reference | 1:PLoS One. 2015 Aug 5;10(8):e0134882. doi: 10.1371/journal.pone.0134882. eCollection 2015. Potential Antileukemia Effect and Structural Analyses of SRPK Inhibition by N-(2-(Piperidin-1-yl)-5-(Trifluoromethyl)Phenyl)Isonicotinamide (SRPIN340).Siqueira RP,Barbosa Éde A,Polêto MD,Righetto GL,Seraphim TV,Salgado RL,Ferreira JG,Barros MV,de Oliveira LL,Laranjeira AB,Almeida MR,Júnior AS,Fietto JL,Kobarg J,de Oliveira EB,Teixeira RR,Borges JC,Yunes JA,Bressan GC, PMID: 26244849 PMCID: PMC4526641 DOI: 10.1371/journal.pone.0134882 </br><span>Abstract:</span> Dysregulation of pre-mRNA splicing machinery activity has been related to the biogenesis of several diseases. The serine/arginine-rich protein kinase family (SRPKs) plays a critical role in regulating pre-mRNA splicing events through the extensive phosphorylation of splicing factors from the family of serine/arginine-rich proteins (SR proteins). Previous investigations have described the overexpression of SRPK1 and SRPK2 in leukemia and other cancer types, suggesting that they would be useful targets for developing novel antitumor strategies. Herein, we evaluated the effect of selective pharmacological SRPK inhibition by N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) on the viability of lymphoid and myeloid leukemia cell lines. Along with significant cytotoxic activity, the effect of treatments in regulating the phosphorylation of the SR protein family and in altering the expression of MAP2K1, MAP2K2, VEGF and FAS genes were also assessed. Furthermore, we found that pharmacological inhibition of SRPKs can trigger early and late events of apoptosis. Finally, intrinsic tryptophan fluorescence emission, molecular docking and molecular dynamics were analyzed to gain structural information on the SRPK/SRPIN340 complex. These data suggest that SRPK pharmacological inhibition should be considered as an alternative therapeutic strategy for fighting leukemias. Moreover, the obtained SRPK-ligand interaction data provide useful structural information to guide further medicinal chemistry efforts towards the development of novel drug candidates. |