HPA-12 is a ceramide analog and inhibitor of ceramide transfer protein (CERT).[1],[2] It inhibits binding of a ceramide probe to the isolated steroidogenic acute regulatory protein-related lipid transfer (START) domain of CERT with an EC50 value of 4 μM in a TR-FRET assay.[2] HPA-12 (2.5 μM) inhibits conversion of the fluorescent ceramide analog C5-DMB-Cer to C5-DMB-sphingomyelin in CHO and HeLa cells.[1] It also inhibits sphingomyelin synthesis in wild-type, but not ATP-dependent ceramide transport-deficient, CHO cells when used at a concentration of 1 μM.
Reference:
[1]. Yasuda, S., Kitagawa, H., Ueno, M., et al. A novel inhibitor of ceramide trafficking from the endoplasmic reticulum to the site of sphingomyelin synthesis. J. Biol. Chem. 276(47), 43994-44002 (2001).
[2]. Santos, C., Fluery, L., Rodriguez, F., et al. The CERT antagonist HPA-12: First practical synthesis and individual binding evaluation of the four stereoisomers. Bioorg. Med. Chem. 23(9), 2004-2009 (2015).