Statins chemical structure

The discovery of these early statins paved the way for the worldwide development of other drugs based on the statin chemical structure (Figure 8.2). Sankyo and Merck directed their later efforts at manufacturing synthetic analogs. Many different statins are currently available for therapeutic use, but lovastatin and mevastatin remain the only fermentation-derived statins. The lovastatin biosynthetic pathway in A. terreus is well understood. This pathway was the first example of a polyketide synthetic pathway in which two fungal type I polyketide synthases work in combination to produce a product (Hendrickson et al., 1999 Kennedy et al., 1999). Since then several statins, including simvastatin, pravastatin, fluvastatin and atorvastatin, have been approved in many countries and are currently used by millions. 

HMG-CoA-Reductase Inhibitors. Figure 2 The chemical structure of the fungal-derived and the synthetic HMG-CoA reductase inhibitors (statins). 

Fig. 3. Chemical structures of HMG-CoA and several statin inhibitors of HMG-CoA reductase. Atorvastatin (Lipitor), simvastatin (Zocor), and pravastatin (Pravachol) are widely prescribed cholesterol-lowering drugs.

Fig. 3.6 Chemical structures of GMi ganglioside and statins. GMi ganglioside (a) atorvastatin (Lipitor) (b) and simvastatin (Zocor) (c)...

Fig. 7.1 Chemical structures of statins. Atorvastatin (Lipitor) (a) cerivastatin (Baycol) (b) ...

Fig. 9.7 Chemical structures of statins. Lipitor (a) crestor (b) zocor (c) pravachof (d) and compactin (e)...

Figure 10.5 High-throughput screening identified G66976 (a) as a suppressor of statin-induced muscle toxicity, (b) Chemical structure of BMS3. (c) The suppressive effects of G66976 are, as in the case of GGPP, lost by further addition of BMS3.

Pepstatin is a strong inhibitor for all acid proteases. It does not inhibit other groups of proteases, such as the neutral and alkaline proteases (1), The unusual potency of pepstatin toward acid proteases is indicated by its which was reported by Kunimoto et al. (2) to be about 1 x 10-IOM for porcine pepsin. Although its chemical structure has been shown (3) to be a hexapeptide which contains two residues of an unusual amino acid, 4-amino-3-hydroxy-6-methylhepatanoic acid (statine), the mode of inhibition by pepstatin is unknown. 

Figure 8 Chemical structures of statins. HMG-CoA analog is highlighted with a dashed circle. Lovastatin and mevastatin are natural statins of fungal origin. Simvastatin and pravastatin are chemically modified derivatives of lovastatin and mevastatin, respectively. Fluvastatin, atorvastatin, cerivastatin (withdrawn from clinical use in 2001), pitavastatin and rosuvastatin are fully synthetic compounds (Schachter, 2005).

HMG-CoA reductase is inhibited by the drug lovastatin, a natural product synthesized by a fungus (Figure 6.14), Lovastatin does not inhibit the enzyme directly it is converted to a compound (similar to the structure of HMG-CoA) that inhibits the enzyme. Ltivastatin, as well as several related compounds in a family of chemicals called statins, have found use in the treatment of cardiovascular disease throughout the world. The study outlined in Figure 6,15 shows the effectiveness of lovastatin in the treatment of cardiovascular disease. The drug lowers... 

Pravastatin and simvastatin are chemically modified derivatives of lovastatin. Atorvastatin, fluvastatin, and rosuvastatin are structurally distinct synthetic compounds. Statins exert their major effect—reduction of LDL levels—through a mevalonic acid-like moiety that competitively inhibits HMG-CoA reductase. By reducing the conversion of HMG-CoA to mevalonate, statins inhibit... 

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