Goodman and Gilman's The
Pharmacological Basis of Therapeutics
14th Edition
Author(s)Laurence Brunton; Bjorn Knollmann
Print ISBN: 9781264258079
,Question 1
A research team isolates several compounds from a medicinal plant that
has been used traditionally to relieve pain. One isolated compound
consistently reduces pain-related behavior in laboratory models. Which
feature best explains why natural products have historically contributed
to drug discovery?
,A. Their biological activity can be observed before the molecular target
is known
B. Their structures are always simple enough for immediate chemical
synthesis
C. Their effects are limited to compounds that act on membrane
receptors
D. Their therapeutic activity guarantees acceptable pharmacokinetics in
humans
Correct Answer:
A. Their biological activity can be observed before the molecular target
is known
Rationale:
A is correct because historically, natural products were often identified
through observed biological or therapeutic effects without prior
knowledge of a specific drug target. This phenotypic approach could
reveal useful compounds even when the underlying molecular
mechanism was unknown.
B is incorrect because many natural products have complex structures
that can be difficult to synthesize or modify.
C is incorrect because natural products may affect many different
classes of biological targets, including enzymes, ion channels, receptors,
and other proteins.
D is incorrect because biological activity does not guarantee favorable
absorption, distribution, metabolism, excretion, safety, or human
efficacy.
Question 2
, A compound produces a measurable biological effect in a cellular assay,
but investigators do not yet know which protein is responsible for the
effect. Which discovery strategy is most consistent with this situation?
A. Phenotypic drug discovery
B. Structure-based drug design
C. Rational dose optimization
D. Clinical pharmacokinetic modeling
Correct Answer:
A. Phenotypic drug discovery
Rationale:
A is correct because phenotypic screening begins with an observable
biological response rather than requiring a predefined molecular target.
The responsible target can be identified later through target
deconvolution or related approaches.
B is incorrect because structure-based design generally starts with
structural information about a specific molecular target.
C is incorrect because dose optimization is primarily a later
pharmacological development activity.
D is incorrect because pharmacokinetic modeling evaluates drug
exposure and disposition rather than identifying an unknown molecular
target.
Question 3
During early drug discovery, investigators identify a molecule that
reproducibly interacts with a disease-relevant target and produces a
measurable effect, but the molecule has poor selectivity and