3,9-bis((ethylthio)methyl)-K-252a

• CAT Number: M092479
• CAS Number: 156177-65-0
• Molecular Formula: C33H33N3O5S2
• Molecular Weight: 615.76
• Purity: ≥95%
• Target: JNK
• Solubility: Limited solubility
• Storage: Store at -20C
• InChI: InChI=1S/C33H33N3O5S2/c1-5-42-15-17-7-9-22-19(11-17)26-27-21(14-34-30(27)37)25-20-12-18(16-43-6-2)8-10-23(20)36-29(25)28(26)35(22)24-13-33(39,31(38)40-4)32(36,3)41-24/h7-12,24,39H,5-6,13-16H2,1-4H3,(H,34,37)/t24-,32+,33+/m1/s1
• InChIKey: SCMLRESZJCKCTC-KMYQRJGFSA-N
• SMILES: O=C([C@@]1(O)C[C@]2([H])N3C4=CC=C(CSCC)C=C4C5=C3C6=C(C7=CC(CSCC)=CC=C7N6[C@@]1(C)O2)C(CN8)=C5C8=O)OC

CEP-1347, also known as KT-7515, 3,9-Bis(etsm)-K-252a, is a potent and selective JNK/SAPK inhibitor potentially for the treatment of neurodegenerative diseases. CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neurons. CEP-1347 increases ChAT activity in culture and promotes cholinergic neurone survival following fimbria-fornix lesion. CEP-1347 inhibits caerulein-induced rat pancreatic JNK activation and ameliorates caerulein pancreatitis.

Reference

1:J Med Chem. 1997 Jun 6;40(12):1863-9. Neurotrophic 3,9-bis[(alkylthio)methyl]-and-bis(alkoxymethyl)-K-252a derivatives.Kaneko M,Saito Y,Saito H,Matsumoto T,Matsuda Y,Vaught JL,Dionne CA,Angeles TS,Glicksman MA,Neff NT,Rotella DP,Kauer JC,Mallamo JP,Hudkins RL,Murakata C, PMID: 9191963 DOI: 10.1021/jm970031d Abstract: A series of 3,9 disubstituted [(alkylthio)methyl]- and (alkoxymethyl)-K-252a derivatives was synthesized with the aim of enhancing and separating the neurotrophic properties from the undesirable NGF (trk A kinase) and PKC inhibitory activities of K-252a. Data from this series reveal that substitution in the 3- and 9-positions of K-252a with these groups reduces trk A kinase inhibitory properties approximately 100- to > 500-fold while maintaining or in certain cases enhancing the neurotrophic activity. From this research, 3,9-bis[(ethylthio)methyl]-K-252a (8) was identified as a potent and selective neurotrophic agent in vitro as measured by enhancement of choline acetyltransferase activity in embryonic rat spinal cord and basal forebrain cultures. Compound 8 was found to have weak kinase inhibitory activity for trk A, protein kinase C1 protein kinase A, and myosin light chain kinase. On the basis of the in vitro profile, 8 was evaluated in in vivo models suggestive of neurological diseases. Compound 8 was active in preventing degeneration of cholinergic neurons of the nucleus basalis magnocellularis (NBM) and reduced developmentally programmed cell death (PCD) of female rat spinal nucleus of the bulbocavernosus motoneurons and embryonic chick lumbar motoneurons.