Annual Health Insurance Premiums And Household Income 1996

Annual Health Insurance Premiums And Household Income, 1996 -2025

Expenditures on Cancer Treatment Total and by Type of Service (in billions)* $100, 0 $88, 3 $90, 0 In 2011 dollars (billions) $80, 0 $74, 8 2001 (adjusted to 2011) $70, 0 $60, 0 $56, 8 $52, 0 $50, 0 $40, 0 $30, 0 $20, 0 $10, 0 $2, 4 $2, 9 $0, 0 Total Ambulatory Visits and Hospital Stays Prescription Medicines Home Health • US Spending on Cancer Treatment continues to rise • Total costs increased 35% from 2001 - 2011 • 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 2

Variations in US Pricing Medical Procedures and Drugs* 25 th Percentile Average 95 th Precentile $12 726 $11 007 $6 214 $5 482 $2 929 $1 145 $532 MRI $4 293 $2 724 $299 $896 CT Scan Abdomen $1 447 Hospital Cost per Day Gleevec • 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 *Data from International Plans 2013 Comparative Price Report • Gleevec has Federation had aof Health much higher success rate for patients than many other high cost drugs 3

Rational Drug Design: A process for drug design which bases the design of the drug upon the structure of its protein target. 1. Structural mapping of the receptor (protein, P) active site 2. Identification of ligands (L) of complementary shape and appropriate functionality 3. 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 IC 50 values

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

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

Binding modes for L-Ca and acetylated derivatives

Surface representation showing Ile 653 side chain in red. Electrostatic map of bound inhibitor

Tyrosine kinase inhibition: Ligand binding and conformational change in c-Kit and c-Abl FEBS Lett. 2009, 583, 2899 -2906.

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.