Adrenergic Family Related Drug Discovery Products
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Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
Membrane proteins known as adrenergic receptors (ARs) mediate the effects of epinephrine and norepinephrine. Neurotransmitters of the sympathetic nervous system and the central nervous system, epinephrine, and norepinephrine serve as hormones released by the adrenal medulla. Humans have nine adrenergic receptor subtypes, which are widely distributed throughout the body and play crucial roles in numerous physiological processes including the reaction to stress, management of heart rate and blood pressure, and metabolic regulation. Along with serving as emergency treatments, epinephrine, and norepinephrine also target adrenergic receptors in the treatment of a wide range of disorders, such as hypertension, hypotension, heart failure, arrhythmias, and asthma.
Fig.1 Adrenergic receptors as drug targets.1
As a pioneer in the field of drug discovery and development, Creative Biolabs can offer high-quality and innovative tools to our customers:
Overview of Adrenergic Receptors
Three major types of the nine adrenergic receptors found in the human body are known as α1 (ADRA1A, ADRA1B, ADRA1D), α2 (ADRA2A, ADRA2B, ADRA2C), and β (ADRB1, ADRB2, ADRB3). Members of a major type are quite similar to one another in terms of sequence and function, yet major types differ from one another in these respects. In the phylogenetic tree of GPCRs, the 42 members of the aminergic receptor subfamily, which include all adrenergic receptors, form a single clade. A conserved D3.32 creates a salt bridge to the positively charged amino group in the ligand in the orthosteric location, while Y7.43 and W7.40 stabilize this salt bridge by a hydrogen bond and - interactions. The aminergic receptors bind monoamine neurotransmitters, acetylcholine, or trace amines. Due to the same ligand recognition mechanism, aminergic receptors frequently exhibit polypharmacology, or drug interactions with numerous targets. As a result, selectivity is a key consideration in the development of drugs targeting aminergic receptors.
Fig.2 Mechanisms of ligand recognition by adrenergic receptors.1
Mechanisms of Adrenergic Receptors
- α Adrenergic Receptors
Structures of α2AAR, α2CAR, and α2BAR in active and inactive states, respectively, are disclosed. More π-π or cation-π and fewer hydrogen bonds are involved in the binding of both agonist and antagonist to α2 adrenergic receptors. Positively charged planar groups, including imidazole, imidazoline, and guanidine, are common in agonists and some antagonists and fit well in this enclosed pocket. In inactive structures, the antagonist pushes the "lid" F7.39 up to another rotamer, enlarging the pocket to provide room for bigger ligands. Piperazine derivatives as α1 antagonists and indole alkaloids with numerous fused rings as α2 antagonists are two examples of ligands with such chemical characteristics that are now employed in therapeutic settings.
- β Adrenergic Receptors
An agonist for the β2AR or β1AR establishes a hydrogen bond with S5.46, bringing TM5 closer to TM3/6. In contrast, an antagonist lacks this hydrogen bond and has a propensity to fill the void with a hydrophobic moiety, impeding the mobility of TM5. All β2/β1 agonists and antagonists exhibit this mechanism.
References
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Wu, Yiran, Liting Zeng, and Suwen Zhao. "Ligands of adrenergic receptors: a structural point of view." Biomolecules 11.7 (2021): 936.
Distributed under CC BY 4.0, extracted parts from original Figure 1 and Figure 2.
