CCPA (biochemistry)

2-Chloro-N⁶-cyclopentyladenosine (CCPA) is a specific receptor agonist for the Adenosine A1 receptor.^[1] It is similar to N⁶-cyclopentyladenosine. Initially developed to probe the physiological and pharmacological roles of adenosine receptors, CCPA has become a pivotal tool in cardiovascular and neurological research. Due to CCPA's high affinity for Adenosine A1 receptors, its tritiated derivative [³H]CCPA can be used as a diagnostic tool for detecting the receptors in tissue with low receptor density.

CCPA

Names
IUPAC name 2-Chloro-N6-cyclopentyladenosine
Systematic IUPAC name (2R,3R,4S,5R)-2-[2-Chloro-6-(cyclopentylamino)-9H-purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
Identifiers
CAS Number	37739-05-2 Y
3D model (JSmol)	Interactive image
Abbreviations	CCPA
ChEMBL	ChEMBL284969 Y
ChemSpider	110356 Y
IUPHAR/BPS	374
MeSH	2-chloro-N(6)cyclopentyladenosine
PubChem CID	123807
CompTox Dashboard (EPA)	DTXSID00958774
InChI InChI=1S/C15H20ClN5O4/c16-15-19-12(18-7-3-1-2-4-7)9-13(20-15)21(6-17-9)14-11(24)10(23)8(5-22)25-14/h6-8,10-11,14,22-24H,1-5H2,(H,18,19,20)/t8-,10-,11-,14-/m1/s1 Y Key: XSMYYYQVWPZWIZ-IDTAVKCVSA-N Y InChI=1/C15H20ClN5O4/c16-15-19-12(18-7-3-1-2-4-7)9-13(20-15)21(6-17-9)14-11(24)10(23)8(5-22)25-14/h6-8,10-11,14,22-24H,1-5H2,(H,18,19,20)/t8-,10-,11-,14-/m1/s1 Key: XSMYYYQVWPZWIZ-IDTAVKCVBF
SMILES Clc1nc(c2ncn(c2n1)[C@@H]3O[C@@H]([C@@H](O)[C@H]3O)CO)NC4CCCC4
Properties
Chemical formula	C15H20ClN5O4
Molar mass	369.80 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Chemical Structure and Properties

CCPA is chemically characterized by the addition of a chlorine atom at the 2-position and a cyclopentyl group at the N⁶ position of the adenosine molecule. These modifications enhance its receptor selectivity and binding affinity. The molecular formula of CCPA is C₁₅H₁₉ClN₅O₄, with a molecular weight of approximately 367.80 g/mol.

Pharmacological Profile

Affinity and Selectivity for Adenosine Receptors

CCPA exhibits a high binding affinity for A₁ adenosine receptors. In rat brain membranes, it demonstrated a K_i value of 0.4 nM, indicating potent interaction. Its selectivity is underscored by a significantly lower affinity for A_2A receptors, with a K_i value of 3,900 nM, reflecting nearly 10,000-fold selectivity for A₁ over A_2A.^[2][3]

Functional Effects

As an A₁ receptor agonist, CCPA effectively inhibits adenylate cyclase activity. In rat adipocyte membranes, it achieved an IC₅₀ of 33 nM, demonstrating its potency. Conversely, its influence on A_2A receptors is minimal, requiring much higher concentrations to elicit comparable effects.

Interaction with A₃ Adenosine Receptors

Interestingly, while CCPA acts as an agonist at A₁ receptors, it functions as a moderate antagonist at human A₃ adenosine receptors. Studies using Chinese hamster ovary cells expressing human A₃ receptors revealed that CCPA binds with a K_i of 38 nM but does not activate the receptor. Instead, it competitively inhibits the effects of A₃ receptor agonists, highlighting its dual role depending on the receptor subtype.^[2][4]

Applications in Biomedical Research

CCPA's selectivity and efficacy make it an invaluable tool in exploring adenosine receptor functions. In cardiovascular studies, it has been employed to investigate A₁ receptor-mediated cardioprotective mechanisms, including modulation of heart rate and ischemic responses (Ischemia). In neurological contexts, CCPA aids in elucidating the role of A₁ receptors in neurotransmission and neuroprotection. Additionally, its antagonistic properties at A₃ receptors provide insights into the complex interplay between different adenosine receptor subtypes.

2-Chloro-N⁶-cyclopentyladenosine (CCPA) stands out as a potent and selective adenosine A₁ receptor agonist with unique antagonistic effects on A₃ receptors.^[5] Its distinct chemical structure underpins its receptor specificity, rendering it a crucial compound in cardiovascular and neurological research. Ongoing studies continue to uncover its potential therapeutic applications and deepen our understanding of adenosine receptor pharmacology.