David A. Matthews Wins the 2007 LAS Alumni Achievement Award

Date

02/11/07

David Matthews
PhD, 1971

In 1984, researchers first isolated the HIV virus, the culprit behind the AIDS epidemic that was spreading panic across the United States. It was also the year that a group of scientists formed a small start-up company known as Agouron Pharmaceuticals—a company that would go on to develop one of the most effective drugs to battle the HIV virus.

David Matthews, who received his PhD in chemistry from the University of Illinois in 1971, was the scientific founder of Agouron. He is also a 2007 winner of the LAS Alumni Achievement Award.

As Matthews recalls, “In the mid-’80s, the National Institutes of Health (NIH) was in a panic mode trying to figure out ways to develop drugs that could have an effect on HIV.”

Agouron became part of an elite group of five research centers that received a grant from NIH to face this daunting challenge. This seed funding eventually led to the drug Viracept, which Agouron discovered and developed, rapidly becoming the leading HIV protease-targeted drug.

When Viracept was introduced in 1997, “it was an astounding success,” Matthews says. Viracept, along with a few other HIV drugs, became part of the first “cocktails” given to AIDS patients that “really knocked their viral loads down to the point where they could resume fairly normal lives,” he says. “These people had been given a death sentence. But all of a sudden, they could resume their lives.”

What’s more, Viracept generated $700 million in sales the first year it was introduced, setting a record for any biotech product.

Viracept works by binding to and inactivating a protease, which the HIV virus needs to replicate. But this drug might never have come about had it not been for the groundwork that Matthews laid as a student at U of I and during 15 years at the University of California at San Diego (UCSD).

Matthews credits U of I with giving him in-depth training in the x-ray methods that became crucial to his future work. After graduating from U of I, he took a position in the Chemistry Department at UCSD, where he worked with x-ray crystallography, a tool of choice for determining molecular structures at the atomic level.

Matthews used this method to figure out how various known drugs bound potently and, in some cases, selectively to different species of an enzyme called dihydrofolate reductase (DHFR), required for living cells to replicate. A drug that binds well to bacterial DHFR without binding to the corresponding human enzyme makes it possible to selectively kill bacteria.

When confronted with the AIDS crisis, Matthews realized they could use the same technique to study the structure of molecules in creating new drugs. Prior to this, the approach to developing drugs that knocked out bacteria and viruses was much more random.

“You exposed bacteria to many different chemicals, looked for the one that killed them, and hoped they also didn’t kill the host,” he explains. “It was pretty hit and miss.”

Since then, many companies, including large pharmaceutical companies such as Pfizer and Merck, use similar approaches in drug discovery.

In 1999, the company that Matthews helped found, Agouron, merged with Warner-Lambert, which was subsequently purchased by Pfizer in 2000; it is now one of Pfizer’s four research and discovery sites worldwide. Matthews retired from the company in 2005, but the research continues. He currently works with two organizations in discovering and developing medicines for diseases in developing countries.

One effort is through the public-private partnership Medicines for Malaria Venture (MMV), the broadest and most extensive organization funding malaria research/drug development in the world. Matthews serves on their Expert Scientific Advisory Committee and works as a consultant on several individual MMV drug discovery projects.

One of these projects will be delivering an exciting new malaria-fighting drug candidate for clinical trials later this year. Malaria accounts for at least a million deaths worldwide each year, say the Centers for Disease Control and Prevention.

Matthews also works on the steering committee for the Special Program for Research and Training in Tropical Diseases, which targets 10 tropical diseases. Staying a step ahead of these diseases is tough, Matthews says, for the simple reason that malaria and other infectious diseases eventually develop resistance. As a result, scientists must find new drugs roughly every six or seven years.

The same is true for their AIDS drug Viracept. Although Viracept is still used by tens of thousands of patients in parts of the world where resistance is not yet a factor, Matthews says that a second-generation of protease inhibitors is now doing the job in the United States.

Courtesy of LAS News

Custom Tags

Directory

scheelinAlexander
Scheeline
bjmccallBenjamin
McCall
cmartn10Calgary
Martin
r-gennisRobert
Gennis
j-gerltJohn
Gerlt
sgranickSteve
Granick
mgruebelMartin
Gruebele
hergenroPaul
Hergenrother
huangRaven
Huang
mlkraftMary
Kraft
leckbandDeborah
Leckband
yi-luYi
Lu
martinisSusan
Martinis
snairSatish
Nair
eoldfielEric
Oldfield
rienstraChad
Rienstra
cmsCharles
Schroeder
zanZaida
Luthey-Schulten
sksScott
Silverman
s-sligarStephen
Sligar
zhao5Huimin
Zhao
mselfba2Michelle
Self-Ballard
pbraunPaul
Braun
mdburkeMartin
Burke
jeffchanJefferson
Chan
sdenmarkScott
Denmark
dlottDana
Dlott
foutAlison
Fout
agewirthAndrew
Gewirth
ggirolamGregory
Girolami
shs3Sharon
Hammes-Schiffer
sohirataSo
Hirata
kamihullKami
Hull
jainPrashant
Jain
jkatzeneJohn
Katzenellenbogen
nmakriNancy
Makri
douglasmDouglas
Mitchell
jsmooreJeffrey
Moore
murphycjCatherine
Murphy
r-nuzzoRalph
Nuzzo
dimerPhilip
Phillips
rauchfuzThomas
Rauchfuss
joaquinrJoaquín
Rodríguez-López
jrogersJohn
Rogers
sarlahDavid
Sarlah
kschweizKenneth
Schweizer
jsweedleJonathan
Sweedler
vddonkWilfred
van der Donk
renskeRenske
van der Veen
vuraweisJosh
Vura-Weis
mcwhite7M.
White
sczimmerSteven
Zimmerman
beakPeter
Beak
wklemperWalter
Klemperer
jdmcdonaJ.
McDonald
mvp11Michael
Pak
pogoreloTaras
Pogorelov
mshen233Mei
Shen
dewoonDavid
Woon
wboulangWilliam
Boulanger
rxbRohit
Bhargava
qchen20Qian
Chen
jianjuncJianjun
Cheng
hy66Hong
Yang
andinomaJosé
Andino Martinez
decosteDonald
DeCoste
thhuangTina
Huang
tjhummelThomas
Hummel
dkellDavid
Kell
doctorkMichael
Koerner
marvilleKelly
Marville
crrayChristian
Ray
tlbrownTheodore
Brown
rmcoatesRobert
Coates
thdjrThom
Dunning,
dykstraClifford
Dykstra
j-jonasJiri
Jonas
j-lisyJames
Lisy
shapleyJohn
Shapley
pshapleyPatricia
Shapley
awieckowAndrzej
Wieckowski
zumdahl2Steven
Zumdahl
ksuslickKenneth
Suslick
jlbearJodi
Bear
jcoxJenny
Cox
ealthausEllen
Althaus
staciryStaci
Ryan
sqdSean
Drummond
dmillsDouglas
Mills
sheeleySarah
Sheeley
jsmaddenJoseph
Madden
cknight4Connie
Knight
schulzeHeather
Schulze
slangleySamantha
Langley
ssmurrayStar
Murray
kbaumgarKeena
Finney
adkssnBeatrice
Adkisson
bmylerBeth
Myler
trabari1Katie
Trabaris
kewatsonKaren
Watson
strussTheresa
Struss
metclfKara
Metcalf
ljohnso2Lori
Johnson
jlwJamison
Lowe
jenruslJennifer
Russell
lchenoweLeslie
Chenoweth
jcfJonathan
Freiman
wdedoWolali
Dedo
ebielserElaina
Kutz
spinnerDavid
Spinner
plblumPatricia
Simpson
stevens2Chad
Stevens
lsagekarLori
Sage-Karlson
bertholdDeborah
Berthold
kecarlsoKathryn
Carlson
tlchen4Timothy
Chen
sdesmondSerenity
Desmond
angelaecAngela
Crawford
hsahmed3Hajira
Ahmed
kakinsKenye
Akins
asali3Arzeena
Ali
axelson2Jordan
Axelson
bai11Yugang
Bai
scbakerStephanie
Baker
duffin2Kevin
Duffin
duttadDebapriya
Dutta
pflotschPriscila
Falagan Lotsch
iflemingIan
Fleming
dgrayDanielle
Gray
thennes2Thomas
Hennessey
mhettingMary Jo
Hettinger
holdaNancy
Holda
holler2Jordan
Holler
aibarrAlejandro
Ibarra
kimshSung Hoon
Kim
kocherg2Nikolai
Kocherginsky
philipk2Philip
Kocheril
dlee106David
Lee
legare2Stephanie
Legare
alewandoAgnieszka
Lewandowska
qianliliQianli
Li
bdmccallBirgit
McCall
smccombiStuart
McCombie
jdm5Justin
McGlauchlen
egmooreEdwin
Moore
myerscouKathleen
Myerscough
snalla2Siva
Nalla
oraham2Aaron
Oraham
lah5LeeAnn
Pannebaker
poonawa2Maria
Poonawalla
rrollerR.
Roller
romanovaElena
Romanova
roubakhiStanislav
Rubakhin
vsfVictoria
Shepherd-Fortner
shvedalxAlexander
Shved
asoudaAlexander
Soudakov
ktsween2Kalee
Sweeney
sktarterSamantha
Tarter
aathoma2Andy
Thomas
kwilhelKaren
Wilhelmsen
wilkeyRandy
Wilkey
luxu3Lu
Xu
yuanyao4Yuan
Yao
silongSilong
Zhang
schlembaMary
Schlembach
emccarr2Elise
McCarren
cmercierChristen
Mercier
atimpermAaron
Timperman
niesShuming
Nie
hshanHee-Sun
Han
mmgMutha
Gunasekera