How are medicines developed?

What is it? What’s inside?

What is inside a medicine?

Active ingredient It looks for the therapeutic target to have an effect and cure the disease Therapeutic target

Active ingredient It looks for the therapeutic target to have an effect and cure the disease

How are medicines developed?

The search for a medicine is a long (10-25 years), complex and expensive process consisting of several stages. DRUG R&D (2-10 years) CLINICAL DEVELOPMENT PHASE I  PHASE II  PHASE III Launch of the drug PHASE IV Launch of the drug PHASE IV DEVELOPMENT SEQUENCE IN THE SEARCH FOR A MEDICINE PRECLINICAL STUDIES (2-6 years) In vitro/In vivo

A drug candidate can be discovered in different ways: ? HOW IS A DRUG CANDIDATE DISCOVERED?

A drug candidate can be discovered in different ways: Chemical modification Serendipity chance Massive screening Rational design HOW IS A DRUG CANDIDATE DISCOVERED?

WE NOW HAVE A DRUG CANDIDATE!

A thorough and complete preclinical study is required before we can test a drug in humans: These preclinical studies include: – Stability and toxicity studies – In-vitro tests ( proteins, cells, tissues and organs ) – In-vivo tests ( animals ) PRECLINICAL DEVELOPMENT ©Parc Científic Barcelona. Author: J. Planagumà

Clinical development is the longest and most costly part of the search for new medicines. It consists of three phases: PHASE I PHASE II PHASE III Healthy volunteers Safety and dose Patients ( ) (drug or placebo) Efficacy and side effects Patients ( ) Long-term effects CLINICAL DEVELOPMENT

If the drug has successfully passed the three clinical phases, it is launched on the market, but the study continues (Phase IV) PHASE II PHASE III PHASE IV PHASE I MARKET AND FINALLY… THE DRUG IS LAUNCHED ON THE MARKET!

SEARCH for DRUGS for PARKINSON’S DISEASE The Barcelona Science Park research project

Parkinson’s disease (PD) is a chronic and progressive movement disorder characterised by: – Coordination problems – Slowed movements – Generalised tremor It is the second most common neurodegenerative disease and affects 1-2% of people over 60. There are currently more than 4 million people suffering from PD worldwide. INTRODUCTION – WHAT IS PARKINSON’S DISEASE?

Our brain is our body’s control centre and the cells responsible for it are called neurons. These cells self- regenerate very slowly. Neurotransmitters are special chemical compounds that enable neurones to “talk to each other” and communicate. INTRODUCTION – PARKINSON’S DISEASE, CAUSES

We still do not know what causes Parkinson’s disease, but we do know that it is due to the loss or incorrect functioning of the neurons responsible for producing dopamine, a neurotransmitter. Dopamine is responsible for transmitting the signals required to control the movement of our muscles. A dopamine deficiency therefore leads to an imbalance in neuronal transmission, preventing neurons from communicating properly. This leads to a loss of motor function. Dopamine  Control of movement Low dopamine levels  Difficulties in the control of movement Dopamine  Control of movement Low dopamine levels  Difficulties in the control of movement INTRODUCTION – PARKINSON’S DISEASE, CAUSES

The way to treat the disease’s progression is by taking oral medicines. The most commonly used medicine today is levodopa, or L-dopa, which consists of a chemical compound that the brain uses to produce dopamine. INTRODUCTION – PARKINSON’S DISEASE, TREATMENT tyrosine L-dopa dopamine vesicles with the dopamine transmitter dopamine receptor receptor cell synapse

Other medicines, which imitate the effect of dopamine in the brain, are also used. – e.g. bromocriptine, lisuride, pergolide, ropinirole, etc. receptor imitator Cell membrane dopamine Cell response INTRODUCTION – PARKINSON’S DISEASE, TREATMENT

Unfortunately, these medicines have a large number of side effects: – Appearance of involuntary movements and tics – Depression – Hallucinations These medicines also cease to be effective with time. We need to produce new medicines with less side effects that are active for longer periods. INTRODUCTION – PARKINSON’S DISEASE, TREATMENT

In the Barcelona Science Park, on the Combinatory Chemistry Platform, scientists are working on the synthesis of new compounds that can be used as therapeutic agents in the treatment of neurodegenerative diseases such as Parkinson’s or Schizophrenia that are: – More active – Less toxic RESEARCH, SYNTHESIS OF DRUGS FOR THE TREATMENT OF PARKINSON’S DISEASE

A drug cocktail is currently administered to increase the efficacy of these anti-Parkinson’s agents. The objective is to synthesise new molecules that are more effective or have less side effects. Anti-Parkinson’s agents Drug cocktail A single drug RESEARCH, SYNTHESIS OF DRUGS FOR THE TREATMENT OF PARKINSON’S DISEASE

Cell response New drug RESEARCH, SYNTHESIS OF DRUGS FOR THE TREATMENT OF PARKINSON’S DISEASE

AD (±)-PPHT A D XAC-COOH RESEARCH, DESIGN AND SYNTHESIS OF NEW MOLECULES

HOW DO WE SYNTHESISE THESE NEW MOLECULES IN THE LAB?

27 HOW DO WE SYNTHESISE THESE NEW MOLECULES IN THE LAB? days reflux in EtOH

28 1.Chemical reaction HOW DO WE SYNTHESISE THESE NEW MOLECULES IN THE LAB?

2. Isolation and purification of the product 3. Characterisation of the product HOW DO WE SYNTHESISE THESE NEW MOLECULES IN THE LAB?

WHAT ARE WE GOING TO DO TODAY?

Chemical reaction HOW DO WE SYNTHESISE THESE NEW MOLECULES IN THE LAB? days reflux in EtOH

Chemical reaction Isolation of product by filtration Characterisation of product by chromatography  ? WHAT ARE WE GOING TO DO TODAY?

Let’s research!