383418-30-2
Chemical Structure
HPA-12
- CAS No.: 383418-30-2
- Formula:C22H37NO3
- Molecular Weight:363.53
IUPAC Name: N-((2R,4S)-1,4-dihydroxy-4-phenylbutan-2-yl)dodecanamide
InChIKey: YCAKBKAOFSILDC-RTWAWAEBSA-N
SMILES: CCCCCCCCCCCC(N[C@@H](CO)C[C@H](O)C1=CC=CC=C1)=O
Biological Activity: HPA-12 is a blood-brain barrier-permeable small-molecule inhibitor of ceramide transfer protein (CERT) with four stereoisomers (the (1R,3R)-stereoisomer exhibits the highest activity). HPA-12 blocks the transport of ceramide from the endoplasmic reticulum to the Golgi apparatus by binding to the START domain of CERT, leading to intracellular ceramide accumulation and inhibition of sphingomyelin (SM) synthesis. HPA-12 induces endoplasmic reticulum stress via the GRP78/ATF6/CHOP axis and activates mitochondrial autophagy, thereby inhibiting cell growth and inducing apoptosis. In in vivo experiments, HPA-12 significantly reduces the leukemia burden and splenomegaly in mouse models of acute myeloid leukemia (AML) and prolongs survival. HPA-12 is applicable for the research of lipid metabolism in acute myeloid leukemia and Alzheimer's disease[1][2][3].
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HPA-12 | 99.4% | HPA-12 is a blood-brain barrier-permeable small-molecule inhibitor of ceramide transfer protein (CERT) with four stereoisomers (the (1R,3R)-stereoisomer exhibits the highest activity). HPA-12 blocks the transport of ceramide from the endoplasmic reticulum to the Golgi apparatus by binding to the START domain of CERT, leading to intracellular ceramide accumulation and inhibition of sphingomyelin (SM) synthesis. HPA-12 induces endoplasmic reticulum stress via the GRP78/ATF6/CHOP axis and activates mitochondrial autophagy, thereby inhibiting cell growth and inducing apoptosis. In in vivo experiments, HPA-12 significantly reduces the leukemia burden and splenomegaly in mouse models of acute myeloid leukemia (AML) and prolongs survival. HPA-12 is applicable for the research of lipid metabolism in acute myeloid leukemia and Alzheimer's disease. | ||||||||||||||||||||
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- [1]. Sun X, et al. Targeting ceramide transfer protein sensitizes AML to FLT3 inhibitors via a GRP78-ATF6-CHOP axis. Nat Commun. 2025;16(1):1358. Published 2025 Feb 4. [Content Brief]
- [2]. Crivelli SM, et al. Synthesis, Radiosynthesis, and Preliminary in vitro and in vivo Evaluation of the Fluorinated Ceramide Trafficking Inhibitor (HPA-12) for Brain Applications. J Alzheimers Dis. 2017;60(3):783-794. [Content Brief]
- [3]. Yasuda S, et al. A novel inhibitor of ceramide trafficking from the endoplasmic reticulum to the site of sphingomyelin synthesis. J Biol Chem. 2001;276(47):43994-44002. [Content Brief]
Keywords
