Calphostin C (CAS: 121263-19-2)

C₄₄H₃₈O₁₄

• Potent and highly specific cell permeable protein kinase C (PKC) inhibitor [1]. The inhibition of PKC is light-dependent.
• PKA, PKG, DAG kinase, phospholipase D1 and D2, myosin light chain kinase and c-Src inhibitor.
• Anticancer compound. Inhibits cell proliferation and strongly induces apoptosis in vitro.
• Inducer of endoplasmic reticulum ER-stress.
• Shown to directly and potently block L-type Ca channels.
• Calphostin C specifically inhibits contraction-stimulated glucose transport but not insulin-stimulated glucose transport in skeletal muscle.
• Wnt/β-catenin/lef-1 signaling inhibitor. β-catenin/TCF antagonist. Inhibits Wnt-activated genes in a dose-dependent fashion

1. Calphostins (UCN-1028), novel and specific inhibitors of protein kinase C. I. Fermentation, isolation, physico-chemical properties and biological activities: E. Kobayashi, et al.; J. Antibiot. (Tokyo) 42, 1470 (1989)
2. Calphostins, novel and specific inhibitors of protein kinase C. II. Chemical structures: T. Iida, et al.; J. Antibiot. (Tokyo). 42, 1475 (1989)
3. Use and specificity of staurosporine, UCN-01, and calphostin C as protein kinase inhibitors: T. Tamaoki, et al.; Methods Enzymol. 201, 340 (1991)
4. Inhibition of protein kinase C by calphostin C is light-dependent: R.F. Burns, et al.; BBRC 176, 288 (1991)
5. Calphostin C, a specific protein kinase C inhibitor, activates human neutrophils: effect on phospholipase A2 and aggregation: S. Svetlov & S. Nigam; Biochim. Biophys. Acta 1177, 75 (1993)
6. Inhibition of diacylglycerol kinase by the antitumor agent calphostin C. Evidence for similarity between the active site of diacylglycerol kinase and the regulatory site of protein kinase C: C. Redman, et al.; Biochem. Pharmacol. 50, 235 (1995)
7. Calphostin C, a widely used protein kinase C inhibitor, directly and potently blocks L-type Ca channels: H.C. Hartzell & A. Rinderknecht; Am. J. Physiol. 270, C1293 (1996)
8. Calphostin C synergistically induces apoptosis with VP-16 in lymphoma cells which express abundant phosphorylated Bcl-2 protein: M. Murata, et al.; Cell. Mol. Life Sci. 53, 737 (1997)
9. Calphostin C induces selective disassembly of the Golgi complex by a protein kinase C-independent mechanism: M. Alonso, et al.; Eur. J. Cell Biol. 76, 93 (1998)
10. Growth inhibition induced by Ro 31-8220 and calphostin C in human glioblastoma cell lines is associated with apoptosis and inhibition of CDC2 kinase: M Begemann, et al.; Anticancer Res. 18, 3139 (1998)
11. Calphostin C triggers calcium-dependent apoptosis in human acute lymphoblastic leukemia cells: D.M. Zhu, et al.; Clin. Cancer Res. 4, 2967 (1998)
12. Calphostin C is an inhibitor of contraction, but not insulin-stimulated glucose transport, in skeletal muscle: J. Ihlemann, et al.; Acta Physiol. Scand. 167, 69 (1999)
13. Pharmacokinetic features and metabolism of calphostin C, a naturally occurring perylenequinone with antileukemic activity: C.L. Chen, et al.; Pharm. Res. 16, 1003 (1999)
14. Potent direct inhibition of mammalian phospholipase D isoenzymes by calphostin-c: V.A. Sciorra, et al.; Biochemistry 40, 2640 (2001)
15. Calphostin C as a rapid and strong inducer of apoptosis in human coronary artery smooth muscle cells: K.D. Krueger, et al.; Int. Immunopharmacol. 13, 1751 (2003)
16. Calphostin-C induction of vascular smooth muscle cell apoptosis proceeds through phospholipase D and microtubule inhibition: X.L. Zheng, et al.; J. Biol. Chem. 279, 7112 (2004)
17. Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex: M. Lepourcelet, et al.; Cancer Cell. 5, 91 (2004)
18. Golgi complex disassembly caused by light-activated calphostin C involves MAPK and PKA: J.A. Morgado-Diaz, et al.; Tissue Cell 39, 161 (2007)
19. Killing of cancer cells by the photoactivatable protein kinase C inhibitor, calphostin C, involves induction of endoplasmic reticulum stress: A. Kaul & W.A Maltese; Neoplasia 11, 823 (2009)
20. Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo: R.K. Gandhirajan, et al.; Neoplasia 12, 326 (2010)
21. Investigation of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5,7-diones as small molecule antagonists of β-catenin/TCF transcription: J. Zeller, et al.; Bioorg. Med. Chem. Lett. 23, 5814 (2013)