DRUG DISCOVERY TECHNOLOGY FOR ROSUVASTATIN



TABLE OF CONTENTS

LIST OF FIGURES AND CHARTS3

1.INTRODUCTION:4

1.1.Success of the drug Rosuvastatin and its effectiveness:4

1.2 Structure of Rosuvastatin:5

2.DRUG DISCOVERY PROCESS:6

2.1 Pre-discovery6

2.1.1 Understand the disease6

2.2 Target Identification6

2.3 Target Validation7

2.4 Drug Discovery8

2.5 Early Safety Tests8

2.6 Lead Generation and Optimization9

2.7 Preclinical Testing9

2.8 Clinical Development10

2.9 Approval11

2.10 Market11

3.LIST OF TECHNOLOGIES IN DRUG DISCOVERY PROCESS12

4.WORK PLAN13

5.CONCLUSIONS AND RECOMMENDATIONS:14

6.REFLECTIVE STATEMENT15

6.1 Strengths15

6.2 Weaknesses15

LIST OF FIGURES AND CHARTS

FIGURE 1: STRUCTURE OF ROSUVASTATIN…………………………………...….…….4

FIGURE 2: ROSUVASTATIN CALCIUM……………………………….………….….……5

FIGURE 3: COMPETITION- MARKET SEGMENT………………………....………….….10

CHART 1: FLOW CHART……………………………………………………………………21

INTRODUCTION:

The present paper is concerned in explaining the drug discovery technology of a Rosuvastatin. Rosuvastatin, like other statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors), improves lipid parameters, including lowdensity lipoprotein (LDL), high-density lipoprotein and triglyceride levels(Joneset al., 2010: 152-160). All statins are known to be associated with a spectrum of myopathies ranging from less serious muscle pain and weakness (occurring in about 1%-5% of patients) to more serious myositis with rhabdomyolysis (defined as muscle symptoms, a markedly elevated serum creatinine kinase level, usually more than 10 times the upper limit of normal, with an elevated creatinine kinase level consistent with pigment-induced nephropathy) (Mahla, 2011: 383-90). The rate of statin-induced rhabdomyolysis is low and varies according to the drug used; however, the condition is potentially fatal, resulting in death in about 1 per 6.6 million prescriptions(Olsson et al. , 2011: 1044-1051).

Success of the drug Rosuvastatin and its effectiveness:

Epidemiological studies and large-scale clinical trials with the statin class of cholesterollowering drugs have conclusively shown the association between reduced levels of lowdensity- lipoprotein cholesterol (LDL-C) and decreased morbidity and mortality from coronary heart disease (CHD). But despite these demonstrated benefits of lowering LDL-C levels, many patients receiving cholesterollowering therapies fail to reach the LDL-C levels recommended by current guidelines. The need for more effective cholesterol-lowering has encouraged the greater use of higher doses of established statins, and also prompted efforts to develop more potent statins and drugs with novel modes of action that can be used to achieve greater reductions in LDL-C levels in a broad spectrum of patients(Franken, 2011: 144-148).

Rosuvastatin has a potent low-density lipoprotein cholesterol (LDL-C) lowering action. In addition it has potentially favourable effects on high-density lipoprotein (HDL), non-HDL-C, triglycerides and the apolipoprotein B : A1 ratio. Theoretically, if assumptions about these lipoprotein effects hold true and translate to better cardiovascular outcomes, rosuvastatin could prove to be the most clinically effective statin(Mahla, 2011: 383-90). However, while results from vascular imaging studies are encouraging overall, it is not clear whether these will translate into favourable cardiovascular outcomes because of lack of trial results. There are, as yet, no published mortality and cardiovascular outcome data from randomised, controlled trials to support LDL-C lowering with rosuvastatin rather than other statins. However, the early termination of one outcome trial has recently been announced because of clear benefits announced from rosuvastatin therapy compared with placebo.

Dose-for-dose, rosuvastatin is more effective in lowering LDL-C levels and raising HDL-C levels than atorvastatin, simvastatin or pravastatin. Furthermore, rosuvastatin is reported to have a side-effect profile similar to its competitors. Ultimately, this greater efficacy should drive ...