1. Annual Health Insurance Premiums And Household Income, 1996-2025

2. US Spending on Cancer Treatment continues to rise
Cancer care costs continue to rise at an extremely high rate
US Spending on Cancer Treatment continues to rise
Total costs increased 35% from
Prescription drugs are 11.4% of Cancer Treatment Expenditures
Drug costs alone rose $8 billion in 10 years, an increase of 500%
*Center for Financing, Access, and Cost Trends, AHRQ, Household Component of the Medical Expenditure Panel Survey, 2001 and 2011

3. Prescription Drug costs - 9% of Total US Healthcare Expenditures
US cost of care can vary widely for routine medical procedures, hospital stays, and cancer drugs
Prescription Drug costs - 9% of Total US Healthcare Expenditures
Gleevec has had a much higher success rate for patients than many other high cost drugs
Cost for routine procedures can also vary widely – from CT Scans, to MRIs, to hospital stays these costs can add up quickly for patients
*Data from International Federation of Health Plans 2013 Comparative Price Report

4. Rational Drug Design: A process for drug design which bases the design of the drug upon the structure of its protein target.
Structural mapping of the receptor (protein, P) active site
Identification of ligands (L) of complementary shape and appropriate functionality
Docking of the ligand to the receptor site - predicting a range of PL complexes with different DGPL values
4. Scoring i.e. ranking DGPL and correlating with experimentally determined properties such as IC50 values

5. HIV-1 Integrase Inhibitors
DKAs
DCQ acids; DCT acids
PDP
SQL
Quinolone
derived

6. L-Chicoric Acid and HIV-1 Integrase
Healy et al., J Mol. Graph. Model. 2009, 27 , 14.

7. Binding modes for L-Ca and acetylated derivatives

8. Surface representation showing Ile653 side chain in red.
Electrostatic map of bound inhibitor

9. Tyrosine kinase inhibition: Ligand binding and conformational change in c-Kit and c-Abl
FEBS Lett , 583,

10. A zinc-binding group provides high affinity but low selectivity
ADAM Ligand Design
Major determinant of potency and selectivity. Long chains can provide selectivity.
Wide range of substituents tolerated. Charged polar groups influence bilary excretion.
A zinc-binding group provides high affinity but low selectivity
Wide range of substituents tolerated and are determinants of potency. Steric bulk beneficial for oral availability.