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1 We will begin momentarily at 2pm ET Recordings will be available to ACS members after three weeks Contact ACS Webinars at 1 Have Questions? Why am I muted? Don t worry. Everyone is muted except the presenter and host. Thank you and enjoy the show. Type them into questions box! Contact ACS Webinars at acswebinars@acs.org 2 1

2 Have you discovered the missing element? Find the many benefits of ACS membership! 3 Benefits of ACS Membership Chemical & Engineering ews (C&E) The preeminent weekly news source. EW! Free Access to ACS Presentations on Demand ACS Member only access to over 1,000 presentation recordings from recent ACS meetings and select events. EW! ACS Career avigator Your source for leadership development, professional education, career services, and much more

3 Like us on Facebook! facebook.com/acswebinars 5 How has ACS Webinars benefited you? ACS Webinars allow me to show my students how chemistry is truly related to everything around them - the medicines they take, the foods they eat, the products they utilize, etc. I enjoy participating in the webinars with them to expose them to current topics and so they can listen to scientists working in fields that may interest them. Todd Smeltz, Math & Chemistry Teacher, Upper Dauphin Area School District Be a featured fan on an upcoming webinar! Write to acswebinars@acs.org 6 3

4 youtube.com/acswebinars 7 Hungry for a brain snack? TM ACS Webinets are 2 minute segments that bring you valuable insight from some of our most popular full length ACS Webinars See all the ACS Webinets at youtube.com/acswebinars 8 4

5 Global Expertise, Trusted Standards, Improved Health Utilize Your Expertise Advance Your Profession Improve Drug and Food Quality Improve Public Health Seeking experts in pharmaceutical, biological, and food sciences; pharmacy; medicine; and related disciplines to volunteer for USP s Council of Experts and Expert Committees for the cycle Application Deadline: January 1, 2015: Council of Experts (Expert Committee Chairs) Visit and click the Call for Candidates banner to access information and to create an application account. 9 Beginning in 2014 all recordings of ACS Webinars will be available to current ACS members three weeks after the Live broadcast date. Live weekly ACS Webinars will continue to be available to the general public. Contact ACS Webinars at acswebinars@acs.org 10 5

6 Upcoming ACS Webinars Thursday, December 4, 2014 Salvaging Carbon Dioxide: Finding Value Beyond the Smokestack Dr. Sam Rushing, President, Advanced Cryogenics Dr. Joseph Fortunak, Professor of Chemistry, Howard University Thursday, December 11, 2014 Chemistry & the Economy: 2014 Year- End Review Paul Hodges, Chairman, International echem Dr. William Carroll, Vice President, Industry Issues for Occidental Chemical Corporation Contact ACS Webinars at 11 Optimizing Potency for evirapine: The Drug that Saved Children from AIDS Dr. Rebecca Anderson Freelance Medical Writer and Author Dr. Joseph Fortunak Professor of Chemistry, Howard University Recordings will be available to ACS members after three weeks Contact ACS Webinars at 12 6

7 Optimizing Potency for evirapine: The Drug that Saved Children from AIDS Rebecca J. Anderson, Ph.D. ovember 20, Safe Harbor Statement All data presented in the webinar are in the public domain. All opinions expressed are those of the presenter and should not be assumed to reflect the official corporate position of the American Chemical Society or any pharmaceutical sponsor. 14 7

8 Audience Survey Question What do you remember about the history of HIV/AIDS? I remember seeing people with AIDS I know what HIV/AIDS is, but I don t remember the epidemic I d like to learn more about HIV/AIDS Where I live HIV/AIDS is common 15 Acquired Immune Deficiency Syndrome Human Immunodeficiency Virus CD4 T-helper lymphocytes Pneumocystis pneumonia Kaposi s sarcoma Oral candidiasis (thrush) CMV retinitis Hepatitis Parasitic diarrhea 16 8

9 1996 HAART implementation Audience Survey Question In the United States for the past decade, the number of HIV-infected people has: increased remained constant declined 18 9

10 Mother-to-Child Transmission of HIV infected 20 10

11 ACTG 076: AZT results Catherine Wilfert Connor et al, EJM 331: (1994) 21 11

12 23 ACTG 076: AZT regimen pregnancy labor/delivery postnatal mother Oral, 5x/day Intravenous infant Oral, 4x/day 14 weeks to Term (6-18 hrs.) 6 weeks 24 12

13 Goal: non-nucleoside RT inhibitor HIV-RT enzyme assay High Throughput Screening Shattock and Rosenberg, HIV from biology to prevention and treatment. Cold Spring Harbor Press, 2012, pp pirenzepine O H Gastrozepin M1 selective antagonist O Treatments: Peptic ulcers Gastric secretion Smooth muscle spasm CH

14 H O First active compound IC 50 = 6000 nm CO 2 -t-bu 27 CH 3 O First Lead Compound IC 50 = 350 nm CH

15 CH 3 O IC 50 = 125 nm more potent more soluble dipyrido CH 3-11 ethyl optimal 29 CH 3 O -5 demethylation IC 50 = 125 nm more potent more soluble short acting CH 3-11 deethylation (inactive) 30 15

16 (stable) CH 3 O IC 50 = 120 nm more potent more stable -11 cyclopropyl (stable) 31 (potency) CH 3 nevirapine O H Final Lead Compound IC 50 = 84 nm more potent more stable bioavailability 32 16

17 nevirapine pirenzepine CH 3 H O H O O CH 3 33 Shattock and Rosenberg, HIV from biology to prevention and treatment. Cold Spring Harbor Press, 2012, pp

18 Mother-to-Child Transmission of HIV in utero childbirth infected breastfeeding 35 ACTG 250: Concentration-time plots for infants receiving booster 2 mg/kg dose hr. after birth; mothers received 200 mg. VP, nevirapine; time 0, birth. Mirochnick et al, J Infect Dis 178: (1998) 36 18

19 J. Brooks Jackson Laura Guay 37 13% 25% HIVET 012: Kaplan-Meier estimates of proportion of babies free from HIV-1 infection through 18 months Guay et al, Lancet 354: (1999) 38 19

20 AZT vs. evirapine AZT evirapine Clinical Trial ACTG 076 HIVET 012 Half-life hr. 45 hr. # maternal doses # infant doses Cost $815 $4 39 PEPFAR President George W. Bush announces a new Mother and Child HIV Prevention Initiative in the Rose Garden June 19. Standing by the President from, left to right, are Secretary of Treasury Paul O'eill, Secretary of Health and Human Services Tommy Thompson and Secretary of State Colin Powell

21 South Africa: Activist Pressure 41 Audience Survey Question What percentage of HIV-positive pregnant women in Africa currently receive AIDS drug treatment? 26% 58% 68% 93% 42 21

22 43 For More Details. McFarland Publishing Amazon.com Barnes & oble 44 22

23 Optimizing Potency for evirapine: The Drug that Saved Children from AIDS Dr. Rebecca Anderson Freelance Medical Writer and Author Dr. Joseph Fortunak Professor of Chemistry, Howard University Recordings will be available to ACS members after three weeks Contact ACS Webinars at 45 Upcoming ACS Webinars Thursday, December 4, 2014 Salvaging Carbon Dioxide: Finding Value Beyond the Smokestack Dr. Sam Rushing, President, Advanced Cryogenics Dr. Joseph Fortunak, Professor of Chemistry, Howard University Thursday, December 11, 2014 Chemistry & the Economy: 2014 Year- End Review Paul Hodges, Chairman, International echem Dr. William Carroll, Vice President, Industry Issues for Occidental Chemical Corporation Contact ACS Webinars at 46 23

24 Optimizing Potency for evirapine: The Drug that Saved Children from AIDS Dr. Rebecca Anderson Freelance Medical Writer and Author Dr. Joseph Fortunak Professor of Chemistry, Howard University Recordings will be available to ACS members after three weeks Contact ACS Webinars at 47 How has ACS Webinars benefited you? ACS Webinars allow me to show my students how chemistry is truly related to everything around them - the medicines they take, the foods they eat, the products they utilize, etc. I enjoy participating in the webinars with them to expose them to current topics and so they can listen to scientists working in fields that may interest them. Todd Smeltz, Math & Chemistry Teacher, Upper Dauphin Area School District Be a featured fan on an upcoming webinar! Write to acswebinars@acs.org 48 24

25 youtube.com/acswebinars 49 Benefits of ACS Membership Chemical & Engineering ews (C&E) The preeminent weekly news source. EW! Free Access to ACS Presentations on Demand ACS Member only access to over 1,000 presentation recordings from recent ACS meetings and select events. EW! ACS Career avigator Your source for leadership development, professional education, career services, and much more

26 ACS Webinars does not endorse any products or services. The views expressed in this presentation are those of the presenter and do not necessarily reflect the views or policies of the American Chemical Society. Contact ACS Webinars at 51 Upcoming ACS Webinars Thursday, December 4, 2014 Salvaging Carbon Dioxide: Finding Value Beyond the Smokestack Dr. Sam Rushing, President, Advanced Cryogenics Dr. Joseph Fortunak, Professor of Chemistry, Howard University Thursday, December 11, 2014 Chemistry & the Economy: 2014 Year- End Review Paul Hodges, Chairman, International echem Dr. William Carroll, Vice President, Industry Issues for Occidental Chemical Corporation Contact ACS Webinars at 52 26

We will begin momentarily at 2pm ET. Slides available now! Recordings will be available to ACS members after one week.

We will begin momentarily at 2pm ET. Slides available now! Recordings will be available to ACS members after one week. We will begin momentarily at 2pm ET Slides available now! Recordings will be available to ACS members after one week. www.acs.org/acswebinars Contact ACS Webinars at acswebinars@acs.org 1 Have Questions?

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