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 othe ...

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 Pfize ...

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 ...

research center. The compound is a potent, selective activator of both the human (EC₅₀ = 23 nM) and rat (EC₅₀ = 97 nM) TRPA1 channels. This compound elicits

nociception Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an org ...

in a mouse model through 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 ag ...

of the TRPA1 channel for in-vitro

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 handling ...

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 channel is considered an attractive pain target based on the fact that TRPA1 knockout mice showed near complete attenuation of pain behaviors in some pre-clinical development models.

References

{{Transient receptor potential channel modulators Transient receptor potential channel agonists Aminopyrimidines Pfizer brands Tetrahydropyrans Piperazines Nociception

See also

References