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Vertex Pharmaceuticals is an American Pharmaceutical company based in South Boston, Massachusetts. Vertex was founded in 1989 by Joshua Boger and Kevin J. Kinsella. Vertex was one of the first biotech firms to use an explicit strategy of rational drug design rather than combinatorial chemistry. By 2004, its product pipeline focused on viral infections, inflammatory and autoimmune disorders, and cancer. It maintains headquarters in South Boston, Massachusetts, and two research facilities, in San Diego, California, and Oxford, England. The company's beginnings were profiled by Barry Werth in the 1994 book The Billion-Dollar Molecule and its further development in his 2014 book, The Antidote: Inside the World of New Pharma. In 2009, the company had about 1,800 employees, including 1,200 in the Boston area.In January of 2014, Vertex completed its move from Cambridge, Massachusetts to South Boston, Massachusetts, and took residence in a new, $800 million complex. Located on the South Boston waterfront, it will mark the first time in the company's history that all of the roughly 1,200 Vertex employees in the Greater Boston area will be working together. Wikipedia.

In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR. Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment. Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients. A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment. Source

Ashlock M.A.,Cystic Fibrosis Foundation Therapeutics Inc. | Olson E.R.,Vertex Pharmaceuticals
Annual Review of Medicine | Year: 2011

Cystic fibrosis (CF) is a progressive genetic disease primarily involving the respiratory and gastrointestinal tracts. Multiple therapies directed at CF symptoms and clinical management strategies have emerged from iterative cycles of therapeutics development, helping to change the face of CF from a fatal childhood affliction to a disease in which nearly 50 of U.S. patients are adults. However, as a consequence of therapeutic advances, the burden of CF care is high, and despite progress, most patients succumb to respiratory failure. Addressing the basic defect in CF with systemic small molecules is evolving as a promising approach. A successful collaboration between a voluntary health organization and a pharmaceutical company, complemented by academic investigators and patients, has led to the clinical development of investigational drugs that restore function to defective CFTR protein in various tissues in CF patients. Important activities, leverage points, and challenges in this exemplary collaboration are reviewed with hope that the CF and other genetic disease communities can benefit from the lessons learned in generating new therapeutic approaches in CF. © 2011 by Annual Reviews. All rights reserved. Source

Giroux S.,Vertex Pharmaceuticals
Bioorganic and Medicinal Chemistry Letters | Year: 2013

In the past decade, several kinase inhibitors have been approved based on their clinical benefit for cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. This review will focus on the cases of acquired resistance to EGFR and ALK inhibitors for non-small cell lung cancer patients and BRAF inhibitors for melanoma patients. I will overview the main causes of acquired resistance, and explore the chemical scaffolds as well as combination of drugs, used to tackle these major causes of resistance. © 2012 Elsevier Ltd. All rights reserved. Source

Perola E.,Vertex Pharmaceuticals
Journal of Medicinal Chemistry | Year: 2010

In order to investigate the evolution of binding efficiency in successful drug discovery programs, a data set of 60 lead/drug pairs with known binding affinities has been compiled and analyzed. Low-end thresholds for the binding efficiencies of viable leads and drugs have been derived. On average, the drugs in the set are significantly larger and more potent but have similar lipophilicity relative to their originating leads, suggesting that the ability to maintain low levels of lipophilicity while increasing molecular weight is one of the keys to a successful drug discovery program. A number of examples demonstrate that large increases in binding efficiency from leads to more elaborate drugs sharing the same scaffold can be achieved. The importance of dissecting a lead structure to identify the most efficient fragments and the option of sacrificing binding efficiency to optimize other properties are discussed, and relevant examples are highlighted. © 2010 American Chemical Society. Source

Walters W.P.,Vertex Pharmaceuticals
Journal of Chemical Information and Modeling | Year: 2013

There is no doubt that papers published in the Journal of Chemical Information and Modeling, and related journals, provide valuable scientific information. However, it is often difficult to reproduce the work described in molecular modeling and cheminformatics papers. In many cases the software described in the paper is not readily available, in other cases the supporting information is not provided in an accessible format. To date, the major journals in the fields of molecular modeling and cheminformatics have not established guidelines for reproducible research. This letter provides an overview of the reproducibility challenges facing our field and suggests some guidelines for improving the reproducibility of published work. © 2013 American Chemical Society. Source

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