PHAY0020
UCL SCHOOL OF PHARMACY
MSc Drug Discovery EXAMINATION
PHAY0020
THE PROCESS OF DRUG DISCOVERY (TPODD 1)
TIME ALLOWED: 3 hours
Answer TWO (2) of the FOUR (4) questions
ALL answers must be typed into a single document.
Each question has the same value.
The marks distribution is shown clearly for each part of the question. Answer all
parts of each of the individual question you select.
You are advised to allocate HALF of your time to EACH question.
Notes are permitted in this examination.
Dictionaries are permitted in this examination.
Calculators are permitted in this examination.
TURN OVER
PHAY0020
2
1. Answer BOTH parts of the question
Virtual screening against 5-hydroxytryptamine receptor (5-HT2C) resulted in a
set of ten small molecules as potential agonists.
a) Discuss the key factors involved in the design and evaluation of CNS drugs
and propose a strategy for selection of two compounds for further in vivo
experiments. (60% of marks)
b) Propose the use of two commonly used methods for in vivo evaluati
on of their
CNS penetration and provide the justification for this choice.
(40% of marks)
2. Answer BOTH parts of the question
You are aiming to develop small molecule compounds to target a newly
identified binding pocket adjacent to an activation loop of a protein kinase and
have available both the human apoprotein and homologous ligand bound
structures determined by x-ray crystallography to better than 2.5 resolution.
Significant differences are observed between the apoprotein and homologous
structures with some additional disorder in the target binding pocket.
a) Describe how you might utilise these structures along with molecular
modelling techniques and with the use of molecular mechanics to understand
the observed differences between the two structures and how this can be
used to build a representative binding pocket. Also discuss how you might
explore structural aspects of the binding pocket as a starting point for
structure-based drug design. Include in your answer the limitations of the
methods used. (60% of marks)