Inhibition of sterol biosynthesis by 14α-hydroxymethyl …

Many public health campaigns have focused on reducing the risk of coronary heart disease (CHD) among Americans by educating them on the role cholesterol plays in the development of CHD. As a result, the word "cholesterol" may quickly be associated with CHD and other heart problems. However, cholesterol—a fat-like substance (lipid)—also has essential functions in the body. It provides structure for cell membranes and is a precursor of bile acids (liver secretions that aid fat absorption) and hormones.6

The new compounds were found to inhibit sterol synthesis in mouse fibroblasts in culture.

Consequently, cholesterol has numerous functions in membranes ranging frommetabolism, as a precursor to hormones and vitamins, to providing mechanicalstrength and a control of the phase behavior of membranes ().


Inhibitors of sterol synthesis ..

Sterol metabolism and lymphocyte function: Inhibition …

Fatostatin, a recently discovered small molecule that inhibits activation of sterol regulatory element-binding protein (SREBP), blocks biosynthesis and accumulation of fat in obese mice. We synthesized and evaluated a series of fatostatin derivatives. Our structure–activity relationships led to the identification of -(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide (24, FGH10019) as the most potent druglike molecule among the analogues tested. Compound 24 has high aqueous solubility and membrane permeability and may serve as a seed molecule for further development.


Sterol regulatory element-binding protein - Wikipedia

N2 - Ketaconazole, a broad-spectrum, antifungal drug that is administered orally, has been shown to inhibit sterol synthesis in fungi. When gynecomastia developed in some patients taking this drug, we investigated the effects of ketoconazole on steroid synthesis in humans and in isolated adrenal cells from rats. In healthy humans, the cortisol response to adrenocorticotropic hormone was significantly blunted 4 hours after a 400-mg or 600-mg dose. The inhibition persisted for up to 8 hours and was absent by 16 hours. This finding indicated that adrenal androgen response was reduced. Easily achieved therapeutic concentrations of ketoconazole virtually eliminated corticosterone production by isolated adrenal cells from rats. Although ketaconazole at currently used doses has never been documented to cause clinical hypoadrenalism, caution is urged in high- or multiple-dose trials. The drug may prove useful as an agent to block steroid synthesis.