Wendy Young

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Wendy B. Young is a medicinal chemist and pharmaceutical executive currently employed at Genentech.

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Wendy B. Young, Ph.D.
NationalityAmerican
CitizenshipUSA
Alma mater Princeton University
Scientific career
Doctoral advisor Edward C. Taylor

Education

Young received her B.S. and M.S. from Wake Forest University, working with Prof. Huw Davies. [1] She was co-author on an early application of Davies' rhodium(II) carbenoid insertion - Cope rearrangement chemistry, leading to the total synthesis of three small tropane natural products. [2] Young received her Ph.D. from Princeton in 1993, working with Edward C. Taylor on heterocycles [3] derived from natural pigments, one of which ultimately became pemetrexed [4] (Alimta), [5] an oncology treatment. In her postdoctoral fellowship with Samuel Danishefsky, Young was among one of a handful of groups in the mid-1990s to synthesize paclitaxel (Taxol), [6] a highly-oxegenated terpenoid natural product used to treat cancer.

Career

Despite multiple employment offers on the East Coast of the United States, [1] Young chose to remain in the San Francisco Bay Area for her professional career. From 1995 to 2006, Young worked at Celera Genomics, studying inhibitor compounds of human plasma proteins [7] such as kallikrein and Factors VIIa and IXa. She was recruited to Genentech in 2006, and in 2018 was promoted to Senior Vice President of Small Molecule drug discovery. [1] One of her major research successes was development of a chemistry campaign against Bruton's tyrosine kinase, leading to molecules to potentially treat rheumatoid arthritis and B-cell lymphomas. [8] Her team developed fenebrutinib, currently in Phase II trials for several autoimmune disorders. [9]

Awards

Related Research Articles

Drug discovery

In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.

Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources as the starting materials to produce other novel compounds with distinct chemical and medicinal properties. The novel compounds generally have a high molecular weight or a complex molecular structure, more so than those produced by total synthesis from simple starting materials. Semisynthesis is a means of preparing many medicines more cheaply than by total synthesis since fewer chemical steps are necessary.

Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one of the most important branches of organic chemistry. There are several main areas of research within the general area of organic synthesis: total synthesis, semisynthesis, and methodology.

Chalcone

Chalcone is an aromatic ketone and an enone that forms the central core for a variety of important biological compounds, which are known collectively as chalcones or chalconoids. Alternative names for chalcone include benzylideneacetophenone, phenyl styryl ketone, benzalacetophenone, β-phenylacrylophenone, γ-oxo-α,γ-diphenyl-α-propylene, and α-phenyl-β-benzoylethylene.

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used as chemotherapy for cancer.

Quinazoline is an organic compound with the formula C8H6N2. It is an aromatic heterocycle with a bicyclic structure consisting of two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring. It is a light yellow crystalline solid that is soluble in water. Also known as 1,3-diazanaphthalene, quinazoline received its name from being an aza derivative of quinoline. Though the parent quinazoline molecule is rarely mentioned by itself in technical literature, substituted derivatives have been synthesized for medicinal purposes such as antimalarial and anticancer agents. Quinazoline is a planar molecule. It is isomeric with the other diazanaphthalenes of the benzodiazine subgroup: cinnoline, quinoxaline, and phthalazine. Over 200 biologically active quinazoline and quinoline alkaloids are identified.

K. C. Nicolaou

Kyriacos Costa Nicolaou is a Cypriot-American chemist known for his research in the area of natural products total synthesis. He is currently Harry C. and Olga K. Wiess Professor of Chemistry at Rice University, having previously held academic positions at The Scripps Research Institute/UC San Diego and the University of Pennsylvania.

Wieland–Miescher ketone

The Wieland–Miescher ketone is a racemic bicyclic diketone (enedione) and is a versatile synthon which has so far been employed in the total synthesis of more than 50 natural products, predominantly sesquiterpenoids, diterpenes and steroids possessing possible biological properties including anticancer, antimicrobial, antiviral, antineurodegenerative and immunomodulatory activities. The reagent is named after two chemists from Ciba Geigy, Karl Miescher and Peter Wieland. Examples of syntheses performed using the optically active enantiomer of this diketone as a starting material are that of ancistrofuran and the Danishefsky total synthesis of Taxol.

Danishefsky Taxol total synthesis

The Danishefsky Taxol total synthesis in organic chemistry is an important third Taxol synthesis published by the group of Samuel Danishefsky in 1996 two years after the first two efforts described in the Holton Taxol total synthesis and the Nicolaou Taxol total synthesis. Combined they provide a good insight in the application of organic chemistry in total synthesis.

Paclitaxel total synthesis

Paclitaxel total synthesis in organic chemistry is a major ongoing research effort in the total synthesis of paclitaxel (Taxol). This diterpenoid is an important drug in the treatment of cancer but, also expensive because the compound is harvested from a scarce resource, namely the Pacific yew. Not only is the synthetic reproduction of the compound itself of great commercial and scientific importance, but it also opens the way to paclitaxel derivatives not found in nature but with greater potential.

Epothilone

The epothilones are a class of potential cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials epothilones have better efficacy and milder adverse effects than taxanes.

Receptor tyrosine kinase

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.

Samuel J. Danishefsky is an American chemist working as a professor at both Columbia University and the Memorial Sloan-Kettering Cancer Center in New York City.

Mubritinib

Mubritinib (TAK-165) is a protein kinase inhibitor which was under development by Takeda for the treatment of cancer. It completed phase I clinical trials but appears to have been discontinued, as no new information on the drug has surfaced since December 2008.

LBP-1 (drug)

LBP-1 is a drug originally developed by Organon for the treatment of neuropathic pain, It acts as a potent and selective cannabinoid receptor agonist, with high potency at both the CB1 and CB2 receptors, but low penetration of the blood–brain barrier. This makes LBP-1 peripherally selective, and while it was effective in animal models of neuropathic pain and allodynia, it did not produce cannabinoid-appropriate responding suggestive of central effects, at any dose tested.

Donna M. Huryn is an American medicinal and organic chemist. She received her B.A. (Chemistry) from Cornell University, and Ph.D. in Organic Chemistry from the University of Pennsylvania. She is on the faculty at the University of Pittsburgh’s School of Pharmacy, holds an adjunct appointment in the Department of Chemistry at the University of Pennsylvania, is the principal investigator of the University of Pittsburgh Chemical Diversity Center, and was a visiting fellow in the summer of 2017 at the University of Bologna. She is a fellow of the American Chemical Society, recipient of the ACS Philadelphia Local Section Award, has held a number of elected positions within the American Chemical Society at both the local and national levels, and is 2015 Chair of the Division of Organic Chemistry. She is associate editor of ACS Medicinal Chemistry Letters. She in also an editor of the journal Organic Reactions and co-authored the textbook Medicinal Chemistry and the article "Medicinal Chemistry: Where Are All the Women?" which appeared in the ACS Medicinal Chemistry Letters Journal. Huryn’s research focuses on the design and synthesis of small molecules probes and drugs to treat cancer, neurodegenerative and infectious diseases.

VEGFR-2 inhibitor, also known as kinase insert domain receptor(KDR) inhibitor, are tyrosine kinase receptor inhibitors that reduce angiogenesis or lymphangiogenesis, leading to anticancer activity. Generally they are small, synthesised molecules that bind competitively to the ATP-site of the tyrosine kinase domain. VEGFR-2 selective inhibitor can interrupt multiple signaling pathways involved in tumor, including proliferation, metastasis and angiogenesis.

Xue-Min Cheng is a medicinal chemist, author and pharmaceutical executive best known as the co-author of The Logic of Chemical Synthesis, which formalized retrosynthesis, the concept for which Elias J. Corey won the 1990 Nobel Prize in Chemistry.

Johanna Maria "Hanneke" Jansen is a computational chemistry leader working at Novartis on multiple drug targets. She previously worked at Astra and at Chiron Corporation.

Iwao Ojima

Iwao Ojima is a Japanese-American chemist and university distinguished professor at the State University of New York at Stony Brook. He has been widely recognized for his seminal contributions to a range of chemical research at the multifaceted interfaces of chemical synthesis and life sciences. As rare accomplishments, he has received four National Awards from the American Chemical Society in four different fields of research. He is also serving as the director of the Institute of Chemical Biology and Drug Discovery (ICB&DD), as well as the president of the Stony Brook Chapter of the National Academy of Inventors.

References

  1. 1 2 3 Genentech. "The Molecule Maker". Genentech: Breakthrough science. One moment, one day, one person at a time. Retrieved 2018-10-27.
  2. Davies, Huw M. L.; Saikali, Elie; Young, Wendy B. (1991). "Synthesis of (.+-.)-ferruginine and (.+-.)-anhydroecgonine methyl-ester by a tandem cyclopropanation/Cope rearrangement". The Journal of Organic Chemistry. 56 (19): 5696–5700. doi:10.1021/jo00019a044. ISSN   0022-3263.
  3. "HeteroCycles". www.heterocycles.jp. Retrieved 2018-10-27.
  4. "Princeton chemist Edward C. Taylor, inventor of anti-cancer drug, dies at 94". Princeton University. Retrieved 2018-10-27.
  5. "Alimta Monograph for Professionals - Drugs.com". Drugs.com. Retrieved 2018-10-27.
  6. Masters, John J.; Link, J. T.; Snyder, Lawrence B.; Young, Wendy B.; Danishefsky, Samuel J. (1995-09-01). "A Total Synthesis of Taxol". Angewandte Chemie International Edition in English. 34 (16): 1723–1726. doi:10.1002/anie.199517231. ISSN   0570-0833.
  7. Tang, Jie; Yu, Christine Luong; Williams, Steven R.; Springman, Eric; Jeffery, Douglas; Sprengeler, Paul A.; Estevez, Alberto; Sampang, Jun; Shrader, William (2005-12-09). "Expression, Crystallization, and Three-dimensional Structure of the Catalytic Domain of Human Plasma Kallikrein". Journal of Biological Chemistry. 280 (49): 41077–41089. doi: 10.1074/jbc.M506766200 . ISSN   0021-9258. PMID   16199530.
  8. Wang, Xiaojing; Barbosa, James; Blomgren, Peter; Bremer, Meire C.; Chen, Jacob; Crawford, James J.; Deng, Wei; Dong, Liming; Eigenbrot, Charles (2017-05-03). "Discovery of Potent and Selective Tricyclic Inhibitors of Bruton's Tyrosine Kinase with Improved Druglike Properties". ACS Medicinal Chemistry Letters. 8 (6): 608–613. doi:10.1021/acsmedchemlett.7b00103. ISSN   1948-5875. PMC   5467183 . PMID   28626519.
  9. "A Study to Evaluate the Long-term Safety and Efficacy of Fenebrutinib in Participants Previously Enrolled in a Fenebrutinib Chronic Spontaneous Urticaria (CSU) Study - Full Text View - ClinicalTrials.gov" . Retrieved 2018-10-27.
  10. "Wendy Young, Genentech | William S. Johnson Symposium". johnsonsymposium.stanford.edu. Retrieved 2018-10-27.
  11. "Genentech: Wendy Young | Senior Vice President, Small Molecule Drug Discovery". www.gene.com. Retrieved 2018-10-27.
  12. 2018, 2014. "Executive Committee". www.acsmedchem.org. Retrieved 2018-10-27.CS1 maint: numeric names: authors list (link)