Zaragozic Acid A

Short Summary : rat liver squalene synthase inhibitor

Category : Metabolism|Squalene synthase

Purity : 0.98

CAS Number : 142561-96-4

Formula : C35H46O14

Molecular Weight : 690.73

SMILE : O[C@@H]1[C@H]([C@@]2([C@](C(O)=O)([C@H](O[C@@]1(CCC([C@H]([C@@H](CC3=CC=CC=C3)C)OC(C)=O)=C)O2)C(O)=O)O)C(O)=O)OC(/C=C/[C@H](C[C@H](CC)C)C)=O

Solubility : Soluble in DMSO

Storage : Store at -20°C

Description : Ki: 78 pM for rat liver squalene synthaseThe zaragozic acids (ZAs), which is a family of fungal metabolites containing a novel 4,6,7-trihydroxy-2,8-dioxobicyclo[3.2.1]octane-3,4,5-tricarboxylic acid core, have been independently discovered by two separate groups via screening natural product sources to discover inhibitors of squalene synthase.In vitro: Zaragozic acid A, as well as it two analogs Zaragozic acid B and C were discovered from an unidentified sterile fungal culture, Spororniella intermedia, and Leptodontium elatius, respectively. Zaragozic acid A, B and C were reported to be three potent competitive inhibitors of rat liver squalene synthase with Ki values of 78 pM, 29 pM, and 45 pM, respectively. In addition, Zaragozic acid A, B and C could also inhibite cholesterol synthesis in Hep G2 cells [1]. In vivo: In the mouse model, zaragozic acid A was found to be an inhibitor of acute hepatic cholesterol synthesis (50% inhibitory dose of 200 g/kg). The in-vivo inhibition of squalene synthase was accompanied by an accumulation of label from [3Hjmevalonate into farnesyl diphosphate, farnesol, as well as organic acids. In summary, these data showed the zaragozic acids were a new class of therapeutic agents with potential for the hypercholesterolemia treatment [1]. Clinical trial: Up to now, zaragozic acid A is still in the preclinical development stage.Reference:[1] Bergstrom JD,Kurtz MM,Rew DJ,Amend AM,Karkas JD,Bostedor RG,Bansal VS,Dufresne C,VanMiddlesworth FL,Hensens OD, et al. Zaragozic acids: a family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase. Proc Natl Acad Sci U S A.1993 Jan 1;90(1):80-4.

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