Biochemistry is the study of the chemical processes in living organisms. It deals with the structure and function of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules.
Although there are a vast number of different biomolecules many are complex and large molecules (called polymers) that are composed of similar repeating subunits (called monomers). Each class of polymeric biomolecule has a different set of subunit types.[1] For example, a protein is a polymer whose subunits are selected from a set of 20 or more amino acids. Biochemistry studies the chemical properties of important biological molecules, like proteins, in particular the chemistry of enzyme-catalyzed reactions.
The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membrane transport, and signal transduction.
Since all known life forms that are still alive today are descended from the same common ancestor, they have similar biochemistries, even for matters that seem to be essentially arbitrary, such as handedness of various biomolecules. It is unknown whether alternative biochemistries are possible or practical.
Saturday, April 18, 2009
Tuesday, April 14, 2009
Process of drug discovery
[edit] Discovery
The first step of drug discovery involves the identification of new active compounds, often called "hits", which are typically found by screening many compounds for the desired biological properties. These hits can come from natural sources, such as plants, animals, or fungi. More often, the hits can come from synthetic sources, such as historical compound collections and combinatorial chemistry.
[edit] Optimization
Another step in drug discovery involves further chemical modifications in order to improve the biological and physiochemical properties of a given candidate compound library. Chemical modifications can improve the recognition and binding geometries (pharmacophores) of the candidate compounds, their affinities and pharmacokinetics, or indeed their reactivity and stability during their metabolic degradation. A number of methods have contributed to quantitative metabolic prediction, and a recent example is SPORCalc[1].The quantitative structure-activity relationship (QSAR) of the pharmacophore play an important part in finding lead compounds, which exhibit the most potency, most selectivity, best pharmacokinetics and least toxicity. QSAR involves mainly physical chemistry and molecular docking tools (CoMFA and CoMSIA), that leads to tabulated data and first and second order equations. There are many theories, the most relevant being Hansch's analysis that involves Hammett electronic parameters, steric parameters and logP(lipophilicity) parameters.
[edit] Development
The final step involves the rendering the lead compounds suitable for use in clinical trials. This involves the optimization of the synthetic route for bulk production, and the preparation of a suitable drug formulation.
[edit] Training in medicinal chemistry
Many workers in the field do not have formal training in medicinal chemistry. Graduate (postgraduate) level programs do exist in medicinal chemistry, but frequently the broader education in a chemistry graduate program can provide many of the skills needed
[edit] Discovery
The first step of drug discovery involves the identification of new active compounds, often called "hits", which are typically found by screening many compounds for the desired biological properties. These hits can come from natural sources, such as plants, animals, or fungi. More often, the hits can come from synthetic sources, such as historical compound collections and combinatorial chemistry.
[edit] Optimization
Another step in drug discovery involves further chemical modifications in order to improve the biological and physiochemical properties of a given candidate compound library. Chemical modifications can improve the recognition and binding geometries (pharmacophores) of the candidate compounds, their affinities and pharmacokinetics, or indeed their reactivity and stability during their metabolic degradation. A number of methods have contributed to quantitative metabolic prediction, and a recent example is SPORCalc[1].The quantitative structure-activity relationship (QSAR) of the pharmacophore play an important part in finding lead compounds, which exhibit the most potency, most selectivity, best pharmacokinetics and least toxicity. QSAR involves mainly physical chemistry and molecular docking tools (CoMFA and CoMSIA), that leads to tabulated data and first and second order equations. There are many theories, the most relevant being Hansch's analysis that involves Hammett electronic parameters, steric parameters and logP(lipophilicity) parameters.
[edit] Development
The final step involves the rendering the lead compounds suitable for use in clinical trials. This involves the optimization of the synthetic route for bulk production, and the preparation of a suitable drug formulation.
[edit] Training in medicinal chemistry
Many workers in the field do not have formal training in medicinal chemistry. Graduate (postgraduate) level programs do exist in medicinal chemistry, but frequently the broader education in a chemistry graduate program can provide many of the skills needed
Medicinal or pharmaceutical chemistry is a discipline at the intersection of chemistry and pharmacology involved with designing, synthesizing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. It also includes the study of existing drugs, their biological properties, and their quantitative structure-activity relationships (QSAR). Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for the purpose of medicinal products.
Compounds used as medicines are overwhelmingly organic products. However, metal-containing compounds have been found to be useful as drugs. For example, the cis-platin series of platinium-containing complexes have found use as anti-cancer agents. This type of compounds are known as metal-based drugs.
Medicinal chemistry is a highly interdisciplinary science combining organic chemistry with biochemistry, computational chemistry, pharmacology, pharmacognosy, molecular biology, statistics, and physical chemistry.
Compounds used as medicines are overwhelmingly organic products. However, metal-containing compounds have been found to be useful as drugs. For example, the cis-platin series of platinium-containing complexes have found use as anti-cancer agents. This type of compounds are known as metal-based drugs.
Medicinal chemistry is a highly interdisciplinary science combining organic chemistry with biochemistry, computational chemistry, pharmacology, pharmacognosy, molecular biology, statistics, and physical chemistry.
[edit] Drug legislation and safety
In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements:
The drug must be found to be effective against the disease for which it is seeking approval.
The drug must meet safety criteria by being subject to extensive animal and controlled human testing.
Gaining FDA approval usually takes several years to attain. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a therapeutic effect or desired outcome.[8]
The safety and effectiveness of prescription drugs in the U.S. is regulated by the federal Prescription Drug Marketing Act of 1987.
The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK.
[edit] Education
The study of pharmacology is offered in many universities worldwide.Again, pharmacology education programs differ from pharmacy programs. Students of pharmacology are trained as researchers, studying the effects of substances in order to better understand the mechanisms which might lead to new drug discoveries for example. Whereas a pharmacy student will eventually work in a pharmacy dispensing medications or some other position focused on the patient, pharmacologist will typically work within a laboratory setting.
Some higher educational institutions combine pharmacology and toxicology into a single program as does Michigan State University. Michigan State University offers PhD training in Pharmacology & Toxicology with an optional Environmental Toxicology specialization. They also offer a Professional Science Masters in Integrative Pharmacology
In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements:
The drug must be found to be effective against the disease for which it is seeking approval.
The drug must meet safety criteria by being subject to extensive animal and controlled human testing.
Gaining FDA approval usually takes several years to attain. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a therapeutic effect or desired outcome.[8]
The safety and effectiveness of prescription drugs in the U.S. is regulated by the federal Prescription Drug Marketing Act of 1987.
The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK.
[edit] Education
The study of pharmacology is offered in many universities worldwide.Again, pharmacology education programs differ from pharmacy programs. Students of pharmacology are trained as researchers, studying the effects of substances in order to better understand the mechanisms which might lead to new drug discoveries for example. Whereas a pharmacy student will eventually work in a pharmacy dispensing medications or some other position focused on the patient, pharmacologist will typically work within a laboratory setting.
Some higher educational institutions combine pharmacology and toxicology into a single program as does Michigan State University. Michigan State University offers PhD training in Pharmacology & Toxicology with an optional Environmental Toxicology specialization. They also offer a Professional Science Masters in Integrative Pharmacology
[edit] Medicine development and safety testing
Development of medication is a vital concern to medicine, but also has strong economical and political implications. To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States, the main body that regulates pharmaceuticals is the Food and Drug Administration and they enforce standards set by the United States Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMEA and they enforce standards set by the European Pharmacopoeia.
The metabolic stability and the reactivity of a library of candidate drug compounds, have to be assessed for drug metabolism and toxicological studies. Many methods have been proposed for quantitative predictions in drug metabolism, one example of a recent computational method is SPORCalc[6]. If the chemical structure of a medicinal compound is altered slightly, this could slightly or dramatically alter the medicinal properties of the compound depending on the level of alteration as it relates to the structural composition of the substrate or receptorsite on which it exerts its medicinal effect, a concept referred to as the structural activity relationship (SAR) . This means when a useful activity has been identified, chemists will make many similar compounds called analogues, in an attempt to maximize the desired medicinal effect(s) of the compound. This development phase can take anywhere from a few years to a decade or more and is very expensive.[7]
These new analogues need to be developed. It needs to be determined how safe the medicine is for human consumption, its stability in the human body and the best form for delivery to the desired organ system, like tablet or aerosol. After extensive testing, which can take up to 6 years the new medicine is ready for marketing and selling.[7]
As a result of the long time required to develop analogues and test a new medicine and the fact that of every 5000 potential new medicines typically only one will ever reach the open market, this is an expensive way of doing things, costing millions of dollars. To recoup this outlay pharmaceutical companies may do a number of things:[7]
Carefully research the demand for their potential new product before spending an outlay of company funds.[7]
Obtain a patent on the new medicine preventing other companies from producing that medicine for a certain allocation of time
Development of medication is a vital concern to medicine, but also has strong economical and political implications. To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States, the main body that regulates pharmaceuticals is the Food and Drug Administration and they enforce standards set by the United States Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMEA and they enforce standards set by the European Pharmacopoeia.
The metabolic stability and the reactivity of a library of candidate drug compounds, have to be assessed for drug metabolism and toxicological studies. Many methods have been proposed for quantitative predictions in drug metabolism, one example of a recent computational method is SPORCalc[6]. If the chemical structure of a medicinal compound is altered slightly, this could slightly or dramatically alter the medicinal properties of the compound depending on the level of alteration as it relates to the structural composition of the substrate or receptorsite on which it exerts its medicinal effect, a concept referred to as the structural activity relationship (SAR) . This means when a useful activity has been identified, chemists will make many similar compounds called analogues, in an attempt to maximize the desired medicinal effect(s) of the compound. This development phase can take anywhere from a few years to a decade or more and is very expensive.[7]
These new analogues need to be developed. It needs to be determined how safe the medicine is for human consumption, its stability in the human body and the best form for delivery to the desired organ system, like tablet or aerosol. After extensive testing, which can take up to 6 years the new medicine is ready for marketing and selling.[7]
As a result of the long time required to develop analogues and test a new medicine and the fact that of every 5000 potential new medicines typically only one will ever reach the open market, this is an expensive way of doing things, costing millions of dollars. To recoup this outlay pharmaceutical companies may do a number of things:[7]
Carefully research the demand for their potential new product before spending an outlay of company funds.[7]
Obtain a patent on the new medicine preventing other companies from producing that medicine for a certain allocation of time
[edit] Divisions
Pharmacology as a chemical science is practiced by pharmacologists. Subdisciplines include
clinical pharmacology - the medical field of medication effects on humans
neuro- and psychopharmacology (effects of medication on behavior and nervous system functioning),
pharmacogenetics (clinical testing of genetic variation that gives rise to differing response to drugs)
pharmacogenomics (application of genomic technologies to new drug discovery and further characterization of older drugs)
pharmacoepidemiology (study of effects of drugs in large numbers of people)
toxicology study of harmful effects of drugs
theoretical pharmacology
posology - how medicines are dosed
pharmacognosy - deriving medicines from plants
[edit] Scientific background
The study of chemicals requires intimate knowledge of the biological system affected. With the knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of receptors, to design chemicals that act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function).
A chemical has, from the pharmacological point-of-view, various properties. Pharmacokinetics describes the effect of the body on the chemical (e.g. half-life and volume of distribution), and pharmacodynamics describes the chemical's effect on the body (desired or toxic).
When describing the pharmacokinetic properties of a chemical, pharmacologists are often interested in LADME:
Liberation - disintegration (for solid oral forms {breaking down into smaller particles}), dispersal and dissolution
Absorption - How is the medication absorbed (through the skin, the intestine, the oral mucosa)?
Distribution - How does it spread through the organism?
Metabolism - Is the medication converted chemically inside the body, and into which substances. Are these active? Could they be toxic?
Excretion - How is the medication eliminated (through the bile, urine, breath, skin)?
Medication is said to have a narrow or wide therapeutic index or therapeutic window. This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below its toxic dose. Those with a narrow margin are more difficult to dose and administer, and may require therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumors.
Pharmacology as a chemical science is practiced by pharmacologists. Subdisciplines include
clinical pharmacology - the medical field of medication effects on humans
neuro- and psychopharmacology (effects of medication on behavior and nervous system functioning),
pharmacogenetics (clinical testing of genetic variation that gives rise to differing response to drugs)
pharmacogenomics (application of genomic technologies to new drug discovery and further characterization of older drugs)
pharmacoepidemiology (study of effects of drugs in large numbers of people)
toxicology study of harmful effects of drugs
theoretical pharmacology
posology - how medicines are dosed
pharmacognosy - deriving medicines from plants
[edit] Scientific background
The study of chemicals requires intimate knowledge of the biological system affected. With the knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of receptors, to design chemicals that act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function).
A chemical has, from the pharmacological point-of-view, various properties. Pharmacokinetics describes the effect of the body on the chemical (e.g. half-life and volume of distribution), and pharmacodynamics describes the chemical's effect on the body (desired or toxic).
When describing the pharmacokinetic properties of a chemical, pharmacologists are often interested in LADME:
Liberation - disintegration (for solid oral forms {breaking down into smaller particles}), dispersal and dissolution
Absorption - How is the medication absorbed (through the skin, the intestine, the oral mucosa)?
Distribution - How does it spread through the organism?
Metabolism - Is the medication converted chemically inside the body, and into which substances. Are these active? Could they be toxic?
Excretion - How is the medication eliminated (through the bile, urine, breath, skin)?
Medication is said to have a narrow or wide therapeutic index or therapeutic window. This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below its toxic dose. Those with a narrow margin are more difficult to dose and administer, and may require therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumors.
pharmacology
Pharmacology (from Greek φάρμακον, pharmakon, "drug"; and -λογία, -logia) is the study of drug action.[1] More specifically it is the study of the interactions that occur between a living organism and exogenous chemicals that alter normal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals. The field encompasses drug composition and properties, interactions, toxicology, therapy, and medical applications and antipathogenic capabilities. Pharmacology is not synonymous with pharmacy, which is the name used for a profession, though in common usage the two terms are confused at times. Pharmacology deals with how drugs interact within biological systems to affect function. It is the study of drugs, of the body's reaction to drugs, the sources of drugs, their nature, and their properties. In contrast, pharmacy is a medical science concerned with the safe and effective use of medicines.
The origins of clinical pharmacology date back to the Middle Ages in Avicenna's The Canon of Medicine, Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on the Antedotary of Nicholas.[2] Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period.[3] Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues.[4] The first pharmacology department was set up by Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects.
The origins of clinical pharmacology date back to the Middle Ages in Avicenna's The Canon of Medicine, Peter of Spain's Commentary on Isaac, and John of St Amand's Commentary on the Antedotary of Nicholas.[2] Pharmacology as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period.[3] Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues.[4] The first pharmacology department was set up by Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects.
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