Cancer Drugs Used Today

The American Society of Pharmacognosy

Barry R. O’Keefe, Executive Committee American Society of Pharmacognosy

Brandcenter, Virginia Commonwealth University, Richmond, VA, September 26, 2014 The American Society of Pharmacognosy

Founded in 1959 in Chicago, IL to “promote the growth and development of pharmacognosy, to provide opportunity for association among workers in science, to provide opportunities for presentation of research achievements, and to promote the publication of meritorious research.” The American Society of Pharmacognosy

The Premier Society in the United States Devoted to the Study of Natural Products

• ASP members have been responsible for the discovery of several of the most important anti-cancer drugs used today. • Almost all of the currently used antibiotics have been derived from natural products. • Natural products are also the templates for antiviral, anti-cholesterol, anti-diabetic, anti-malaria and immunosuppressive agents as well as pain medications. • ASP members are also active in chemical ecology, biodiversity, responsible sourcing and sustainable development of plants, animals, microbes and marine organisms. Why Should You Care About Pharmacognosy?

The World’s Forests and Oceans are Rapidly Being Depleted of Unique Species.

Natural Products Research and the ASP in Particular Support Biodiversity Efforts Around the Globe. Why Should You Care About Natural Products?

>50% of antimicrobial and anti-cancer drugs come from natural products.

All Small Molecule Drugs

Most large pharmaceutical companies have eliminated natural product screening from their discovery efforts. A Sample of Approved NP-derived Drugs 2007-2012

Retapamulin Ingenol metubate Omacetaxine mepesuccinate antibiotic basal cell carcinoma chronic myelogenous leukemia 2007 2012 2012 Trabectedin Romidepsin Ovarian, soft-tissue sarcoma T-cell Lymphomas 2007 2009

Ixabepilone Breast Cancer 2007

Less than 1% of biome Mifamurtide Osteosarcoma examined! 2009

Eribulin metastatic breast cancer 2010

Carfilzomib Multiple myeloma Fidaxomicin 2012 antibiotic 2011 Brentuximab, Hodgkin’s lymphoma 2011 So What Kind of Research Are We Talking About? Ziconotide: Used for Pain Management ASP Researchers are on the Forefront of Chemical Ecology and Microbial Genomics ASP Researchers are Making a Difference in the Products You Buy

ASP researchers in Botanical Centers funded by the U.S. Government work to standardize herbal products and confirm their activity in clinical trials Cancer: An Example of the Impact of ASP Members

Gordon Svoboda Svoboda, Wall and Wani are all Honorary isolated Vincristine in Members of the ASP 1961 from the Madagascar periwinkle.

Monroe Wall and Mansukh This class of Wani discovered alkaloids is still Taxol from the the second most Pacific Yew tree. Ken Rinehart’s used class of anti- group isolated cancer drugs. ectinascidin from a sea squirt. It is now To date Taxol is an approved drug the best-selling for ovarian cancer anti-cancer drug ever made. Griffithsin: A Personal Story

• Griffithsia sp. (a red alga) originally collected in New Zealand • Aqueous extract displayed potent anti-HIV activity • Protein component of the extract had an anti-HIV activity <1 g/ml • Griffithsin active against HIV at 0.000000000043 grams per milliliter Griffithsin: A Personal Story

Griffithsin Production in Nicotiana benthamiana

pGRFT Purification

Griffithsin is now headed to clinical trials as an “microbicide” gel for use by women and men to prevent infection by HIV, HSV, HPV and HCV

The Type of Visibility We’d Prefer to Avoid The Ebola Virus

Epidemiology: - First outbreak in Zaire 1976 - Natural host is unknown - Transmission associated with close contact (blood or body fluids) - Current outbreak in Africa is the largest ever recorded, a global crisis

Sign and Symptoms: (Abrupt Onset ) Fever Malaise Chills Loss of appetite Muscle aches Headache Abdominal pain Nausea/ vomiting Maculopaplar rash

Clinical Features: - Incubation period: 4-21 days - Liver function impaired - Bleeding & dysregulated coagulation (clotting) - Morbidity/shock 6-9 days after onset - Case fatality rates high (40-90%) • No apparent immune response in fatal cases • Humanized antibodies currently being used for treatment • Vaccine for Zaire strain in Phase I clinical trial (safety) Efficacy of Griffithsin Against Ebola Zaire

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All Surviving Mice have Permanent Neutralizing Immunity to Ebola Zaire The Type of Visibility We’d Like to Encourage

Report of a scientific meeting (American Chemical Society)

Published in the journal Science

Responsible description of the science (not overly hyped)

The type of publicity we would like to generate from ASP annual meetings The American Society of Pharmacognosy

Potential Areas of Improvement for the ASP:

1. The Name of the Society 2. Membership 3. Organizational Structure 4. Information Dissemination 5. Technical Footprint 6. Annual Meetings 7. Logo and Graphics

We hope that the VCU Brandcenter can help us to improve the recognition of the ASP in both the scientific and lay communities and that this will aid in enhancing membership and connecting with a new generation of scientists. The Name of the Society or What is Pharmacognosy?

This, unfortunately, is always the question!

Pharmacognosy from the original Greek “pharma” drug and “cognosy” knowledge

From Wikipedia:

Pharmacognosy is the study of medicines derived from natural sources. The American Society of Pharmacognosy defines pharmacognosy as the “study of the physical, chemical, biochemical and biological properties of drugs, drug substances or potential drugs or drug substances of natural origin as well as the search for new drugs from natural sources”

The ASP is concerned that most people, even scientists, have no idea what pharmacognosy means. The Name of the Society

The name of the Society must capture the core aspects of the mission of the ASP and be immediately identifiable by scientists and intuitively understandable by the lay public

The name should represent the totality of the interdisciplinary sciences that make up modern research in natural products

It is unusual to change the name of a scientific society, especially after 50 years. We are unlikely to ever change it again.

The Society is increasingly international and we wish to encourage further international growth.

As there have been changes in pharmacognosy over the last 50 years, there will be over the next 50; so the name must be broad enough to encompass the past, the present, and the future. Membership

Current Total Members (2014) = 668 North America = 75% Asia/MidEast/Australia/New Zealand = 14% Europe = 7% Africa = 2% South/Latin America = 2% Membership base = 771 (median paid membership last 5 years) Total membership = 1175 (all who have been members at one point) Current new members number <50 per year and generally only make up for lost members leaving membership stagnant or declining over the last 5 years

ASP members include both scientists involved in research on the isolation and characterization of active molecules from natural sources and those devoted to herbal remedies and the traditional use of medicinal plants for health. Current estimates are that 4.5 billion people world-wide predominantly rely on medicinal plants as their source of medicines. Membership

A complete membership directory with contact information for all ASP members is available on line to members and will be made available to VCU Project Teams to obtain information/opinion from ASP members worldwide (its an iPhone App). Organizational Structure

ASP- main scientific society ASP Foundation – associated non-profit charity Journal of Natural Products – society scientific journal co-published with the American Chemical Society

• Society governed by an elected Executive Committee (4 yr terms) led by a President elected for a 1 year term • Officers include Treasurer and Secretary (5 year terms) and a Vice- president (1 year term prior to becoming president) • Recently 1 permanent employee hired in support of the treasurer and the society in general. • The Foundation is run by an appointed board and treasurer. Information Dissemination

Mainly through two electronic avenues

The ASP Web Site - public access except for member directory

The ASP Newsletter – delivered by email to members and archived on the ASP web site. The ASP Newsletter

• Published electronically four times a year. • Generally over 20 pages of text • No current advertising • Sent to all ASP members by email as part of membership • Produced by a volunteer and co-workers who receive honoraria

An Example of a Most Successful Newsletter

• Chemical and Engineering News

• Published weekly by the American Chemical Society both online and print

• Significant advertising content

• Available only to ACS members

• Produced professionally

• Over 160,000 circulation

The ASP Web Site

• From July 1, 2013 to June 30, 2014 there were 49,418 hits to the web site. • 53% the result of internet searches (Google responsible for 57% • 23% from direct access • 10% referred from the Journal of Natural Products web site • Of the total visits, 28,628 (58%) were logged as new users. • The average user accesses 2.5 pages per visit in just under 3 min. • The US is the source of the greatest number of site visits (70%); Korea (5%), China (5%), Great Britain (3%), France (2%), and Brazil (< 2%) are the origins of the most frequent visits from outside the US. • The visits to the website resulted in 122,058 page views. The home page is the most highly visited page (24%), followed by the ASP employment service (Jobs) pages (18%). Other frequently visited pages are the links to graduate programs (8%), journals (5%), Journal of Natural Products page (5%), and future ASP meetings (4%). Potential Re-design of the Web Page Technical Footprint: The Journal of Natural Products

The Journal of Natural Products (JNP) is the main (only) scientific journal of the ASP JNP is co-published with The American Chemical Society 1082 manuscripts submitted to JNP for publication in 2013 (31% accepted) • highest number submitted • lowest percent accepted • highest impact factor reached Two awards given annually for the best papers published by JNP Annual Meetings

The ASP hosts a scientific symposium every year

Generally >500 people attend the annual meeting

The venue changes every year and is dependent on a volunteer local organizing committee

The meeting is often a source of additional revenue for the Society

Every 5th year the meeting is jointly held with four European Societies (the Pharmacognosy Society of French Speaking Persons (AFERP), the Society for Medicinal Plant Research (GA), the Phytochemical Society of Europe (PSE), and the Italian Society of Pharmacognosy (SIF))

Very little press coverage (scientific or lay) has usually been realized from the annual meeting. Logo and Graphics ASP is a Popular Designation Average American’s Frame of Reference

Author Wade Davis’ Ph.D. A bad movie (24% Rotten mentor at Harvard was Tomatoes) with bad Richard Evans Schultes science (ASP Honorary Member) The American Society of Pharmacognosy

Thank you for your willingness to work with us on re-branding the ASP

and

Thank you for your Attention!