Proteomics Essay

This paper hopes to share insight into the steps that are taken by companies, and the strenuous process behind developing an effective new drug.

There are multiple health concerns worldwide and more and more drugs are needed every day. Many drugs however, are extremely expensive to develop, test, and produce. According to the Tufts Center for the Study of Drug Development (2002), it costs up to $802 million to bring a new drug to the market. In 2002, pharmaceutical companies spent $34 billion in research and development (Center-Watch, 2003). In addition to the costs, the overall time from the discovery to approve and market the drug can take up to 15 years.

Extremely risky drug discovery and development, lengthening development times which increase development cost, return on investments, and generic competitors.

I did not get conclusive data from the gel I made. As you can see in figure 1, the bands that showed up on the gel were too cluttered to be able to measure them. So I could not compare protein bands between the fish species based on our gel. Instead, I used a default gel picture that another group did in the class to get my data. From their gel I was able to compare the different species. Table 1 shows the number of bands that were similar between the different fish species when they were compared. I was able to determine that fish species C (Tuna)

However, it is important to mention that biopharmaceuticals are more expensive than small-molecule drugs, although their use is increasing.[18]

Before any biopharmaceutical company can begin to manufacture a desired product, the company is required by law to establish an adequate facility to support a safe and efficient manufacturing process. The US Food and Drug Administration (FDA) department under the authority of the Federal Food, Drug, and Cosmetic Act determines whether or not a specific manufacturing facility is approved. Furthermore, companies must adhere to the Good Manufacturing Practice Regulations (GMP) specifically those described in ICH Q7 in order to effectively fulfill FDA requirements. The fundamental purpose of the regulations beforehand is to accomplish a system that ensures products are consistently produced and controlled to the highest standards and thus prevent human safety risks that may not be reduced through testing the final

Research indicates that small molecules are the most common and more easier form of drug therapeutics. Small molecules are easier and more cost effective to produce. However because they are chemically produced and are ingested through tablets, it makes it difficult for them to have a lasting affect within the body. Researchers are looking into using biologics as an alternative form of therapeutic for certain diseases. Biologics are naturally synthesised from various sources. It has been known that biologics would have a longer “life expectancy” within the body because it would be given intravenously, directly into the blood stream avoiding it from being broken down by the G1 tract which would occur with a small molecule (Bayer HealthCare,

The discovery from the Scripps Research Institute in Florida shows promising results in tackling down the cause of Parkinson’s, and their outcomes led to a funding by the National Institutional Disorders and Stroke Research (NINDS). Research staff within the campus discovers that many diseases that relate in twisting a protein from its original structure will result in a cellular death but it isn’t due to the deformed shape. According to the article “Scripps Florida Scientists' 'Mad Cow' Discovery” (2015), one primal cause that leads to Parkinson’s is the lack of “NAD+” which later prohibits the proper energy function of the mitochondria. Researchers further delved into the study to find out this is preventable, by providing the misshaped protein

A. SIGNIFICANCE. Our goal is to screen chemical libraries to identify compounds that modulate mitochondrial transport in hippocampal and cortical neurons. This study is significant in four ways: (1) There is an urgent need to develop CNS (Central Nervous System) active drugs. CNS disorders are not only staggeringly complex but are poorly treated diseases (Palmer and Stephenson, 2005). In the United States alone the annual cost for stroke, depression, Schizophrenia and Alzheimer’s disease are currently estimated to be over $250 billion annually (Pangalos et al., 2007). Despite the advances in translational medicine and pharmaceutical research little progress has been made in developing CNS therapeutics. Improving CNS drug discovery efforts is an urgent goal as an estimated 1.5 billion people suffer from CNS-related diseases worldwide. Unfortunately only a handful of new drugs have been brought to the market with very few in the pharmaceutical pipeline (Kissinger, 2011; Schoepp, 2011; Abbot, 2011). The majority of pharmaceutical companies have recently announced a shift from supporting internal drug discovery efforts in favor of academic and government partnerships (Schoepp, 2011). At Scripps Florida we have close interaction of state of the art high throughput small molecule screening and cutting-edge neuroscience research. Thus we are in a unique position to address the challenges in developing CNS therapeutics. (2) Mitochondrial dysfunction is part of the pathophysiology of

* No foreseeable new product in pipeline. Currently takes up to 11,000 compounds to be screened to find one (1) compound to send through final testing (human trials). And even then it’s not guaranteed to make it past the FDA.

Notwithstanding this, dosage forms or pharmaceutical kits/packages that embody a fixed dosage regime that do not involve “any professional decision-making have been accepted as patentable” (Abbvie, at para. 112]; CIPO).

Guanabenz is an α-2 adrenergic receptor, and as such has traditionally been used as a treatment for hypertension. However, it has recently been harnessed as a particularly apt therapeutic tool for mediating prion diseases (Nguyen et al., 2014). Since PD is a proteinopathy whose pathogenesis is also linked to aggregation and spread of toxic misfolded proteins from cell to cell, the anti-prion activity of guanabenz lends itself to the study of PD as a possible therapeutic tool. Specifically, guanabenz inhibits the dephosphorylation of eIF2α, important for prolonging the protective phase of the UPR and decreasing the likelihood of a cell reverting to pro-apoptotic signaling as discussed above. This drug furthermore inhibits the protein folding activity of the ribosome (PFAR), which has been implicated in the appearance and maintenance of misfolded proteins which allow for the amyloid deposition responsible for cell death. However, despite anti-PFAR and anti-prion activity, guanabenz retains α-2 adrenergic side-effects, including weakness and dizziness, which would limit its use in human subjects. Recently a structure-activity relationship was conducted which identified two chemical derivatives found to conserve anti-prion and anti-PFAR activity while lacking undesirable α-2 adrenergic activity: compound 6 and compound 7. By changing the position of a chlorine attachment on the benzene ring of guanabenz, these drugs are viable candidates to test for the treatment of PD (Nguyen et al.,

Domains are different parts of the protein that can function independently of the rest of the protein. Chaperones have an important role in the cell, where they make sure that proteins fold in the correct way, ensuring correct function of the proteins. When a chaperone comes across an incorrectly folded protein, it can refold it or degrade it. Incorrect folding and toxic aggregation of misfolded proteins can lead to severe diseases and participate in neurodegeneration. Since misfolding of proteins can have such serious consequences, it is important that the misfolded proteins are degraded to avoid pathogenesis. Chaperones are therefore a part of the protein quality control called proteostasis. In addition to contributing to the correct folding of proteins, chaperones also participate in unfolding of proteins and in maintaining protein homeostasis - a stable internal environment. Some proteins are quite selective and require a very specific type of chaperone to be folded correctly. The effectiveness of chaperones seems to decline with age, which is why protein-folding diseases are more common among the elderly. This is supported by the observation that decreased levels of molecular chaperone activity have been found in studies done on deceased people who suffered from Parkinson’s disease. Because of the important role that chaperones have in protein folding, they are an attractive target for therapies in diseases that are associated with toxic protein aggregation, like Parkinson’s disease, Alzheimer’s disease (AD) and Huntington’s disease

- As the article mentioned, it is important for us to get our products into the clinic before others do.

Introduction AstraZeneca PLC (AstraZeneca, AZN:NYSE, AZN:LSE) is one of the largest pharmaceutical companies in the world. It was formed in 1999 from the merger of Sweden’s Astra AB and UK’s Zeneca Group plc. Core Activities AstraZeneca is engaged in the discovery, development, manufacturing and marketing of prescription pharmaceuticals and biological products for important areas of healthcare: Cardiovascular, Gastrointestinal, Infection, Neuroscience, Oncology, and Respiratory and Inflammation. One of the key benefits of the merger between Astra and Zeneca is seen as their portfolio of new products in development: AstraZeneca call this their 'product pipeline'.