PF-4840154 is a
pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...
derivative discovered by
Pfizer
Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
at its
Sandwich, Kent
Sandwich is a town and civil parish in the Dover District of Kent, south-east England. It lies on the River Stour and has a population of 4,985. Sandwich was one of the Cinque Ports and still has many original medieval buildings, including sev ...
research center. The compound is a potent, selective activator of both the human (EC
50 = 23 nM) and rat (EC
50 = 97 nM)
TRPA1
Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by the ''Trpa1' ...
channels.
This compound elicits
nociception
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, co ...
in a mouse model through
TRPA1
Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by the ''Trpa1' ...
activation. PF-4840154 is used as a reference
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of the
TRPA1
Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by the ''Trpa1' ...
channel for
in-vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
high-throughput screening
High-throughput screening (HTS) is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handlin ...
purposes, and is superior to
allyl isothiocyanate
Allyl isothiocyanate (AITC) is an organosulfur compound (formula CH2CHCH2NCS). This colorless oil is responsible for the pungent taste of mustard, radish, horseradish, and wasabi. This pungency and the lachrymatory effect of AITC are mediated thr ...
for this use.
The
TRPA1
Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by the ''Trpa1' ...
channel is considered an attractive pain target based on the fact that
TRPA1
Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by the ''Trpa1' ...
knockout mice showed near complete attenuation of pain behaviors in some
pre-clinical development
In drug development, preclinical development, also termed preclinical studies or nonclinical studies, is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug ...
models.
See also
*
ASP-7663
ASP-7663 is a chemical compound which acts as a potent, selective activator of the TRPA1 channel. It has protective effects on cardiac tissue, and is used for research into the function of the TRPA1 receptor.
See also
* JT-010
JT-010 is a chem ...
*
JT-010
JT-010 is a chemical compound which acts as a potent, selective activator of the TRPA1 channel, and has been used to study the role of this receptor in the perception of pain
Pain is a distressing feeling often caused by intense or damaging ...
References
{{Transient receptor potential channel modulators
Transient receptor potential channel agonists
Aminopyrimidines
Pfizer brands
Tetrahydropyrans
Piperazines
Nociception