Eli Lilly and Company was founded in 1876 by Colonel Eli Lilly to produce high quality pharmaceutical products based on science rather than advertisements. Some of Lilly's major products included Prozac, Zyprexa, Humulin insulin, and Ceclor antibiotic. In the 1980s, Lilly adopted genetic engineering and rational drug design, and in the late 1980s began using combinatorial chemistry to accelerate drug development. In 1994, Lilly acquired Sphinx Pharmaceuticals to gain expertise in combinatorial chemistry and high-throughput screening. Lilly used these methods in projects targeting central nervous system disorders like depression and migraine.

1. Eli Lilly and
Company

2. History
Eli Lilly and Company has been in business more than 132 years. The
global, research-based company was founded in May 1876 by Colonel Eli
Lilly in Indianapolis, Ind., in the Midwestern section of the United States. A
38-year-old pharmaceutical chemist and a veteran of the U.S. Civil War,
Colonel Lilly was frustrated by the poorly prepared, often ineffective
medicines of his day. Consequently, he made these commitments to
himself and to society:
- He would found a company that manufactured pharmaceutical products of
the highest possible quality.
- His company would develop only medicines that would be dispensed at
the suggestion of physicians rather than by eloquent sideshow hucksters.
- Lilly pharmaceuticals would be based on the best science of the day.

3. Eli Lilly and Company Major Product
Prozac®, the first major introduction in a new class of
drugs for treatment of clinical depression.
Zyprexa®, now the world's top-selling antipsychotic for the
treatment of schizophrenia
Humulin® insulin identical to that produced by the human
body.
Ceclor®, a member of the cephalosporin family, was
eventually became the world's top-selling oral antibiotic.

4. Innovation in the new drug
development process
19th century, Synthetic chemistry
1980s, genetic engineering and rational drug
discovery
Late 1980s, Combinatorial chemistry

5. Combinatorial chemistry
Combinatorial chemistry is one of the important new
methodologies developed by researchers in the pharmaceutical industry
to reduce the time and costs associated with producing effective and co
mpetitive new drugs.
By accelerating the process of chemical synthesis, this method is having
a profound effect on all branches of chemistry, but especially on drug
discovery. Through the rapidly evolving technology of combi-chemistry, it
is now possible to produce compound libraries to screen for novel bioacti
vities. This powerful new technology has begun to help pharmaceutical c
ompanies to find new drug candidates quickly, save significant money in
preclinical development costs and ultimately change their fundamental a
pproach to drug discovery.

6. Combinatorial chemistry at Lilly
In September 1994, Lilly acquired a
financially strapped biotechnology firm named
Sphinx Pharmaceuticals which had leading
expertise in combinatorial chemistry and high-
throughput screening.

7. Drug discovery for central nervous
system (cns) diseases
In the mid-1990s, roughly one billion people, or
one-fifth of the world’s people, suffered from a
neurological or psychiatric disorder at one point in
their lifetime such as clinical depression, severe
insomnia, and migraine that might predispose
people to suicide.

8. Drug discovery for central nervous
system (CNS) diseases
Many CNS diseases were thought to result
from imbalances of neurotransmitters. Different
neurotransmitters were known to activate different
receptors just as different keys might open up
different doorways.

9. Drug discovery for central nervous
system (CNS) diseases
Various classes of neurotransmitters, such as
dopamine, norepinephrine, and serotonin, were
associated with differing diseases. For example,
Serotonin was associated with a variety of conditions
ranging from depression to insomnia to aggression
to migraine.

10. Drug discovery for central nervous
system (CNS) diseases
-Lilly’s first billion dollar blockbuster antidepressant
drug, Prozac® very selectively boosted levels of
serotonin to exert its therapeutic effects.
-Prozac® had undesirable side-effects such as
sedation, anxiety, and dry mouth.
-Prozac® would come off patent in 2003

11. Lilly’s migraine project
1994:March/April
-“Hot” lead compound found from the screen with
good fit at the serotonin 1f receptor.
-Kaldor gives combinatorial chemistry seminar to
an in-house audience at Lilly that includes Schaus.
This serves as catalyst for Kaldor-Schaus
collaboration.

12. Lilly’s migraine project
1994:March/June
-Improvements upon this lead made using
traditional chemistry. Screening proceeds using an
improved assay, which now tests 50 compounds
per week

13. Lilly’s migraine project
1994:September
-Sphinx acquired. Will take almost another year to
integrate Sphinx’s leading-edge technology in
combichem and high-throughput screening.
1994:December
-Schaus presents seminar on his research to other
CNS research group leaders. Able to demonstrate that
combichem can lead to pure, quantifiable results.

14. Lilly’s migraine project
1995:February
-PTAC (project approval committee) meets to
discuss strategic choices in migraine project.