CCPA (biochemistry)

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 compound

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.

## Chemical Structure and Properties

[edit]

CCPA is chemically characterized by the addition of a chlorine atom at the 2-position and a cyclopentyl group at the N<sup>6</sup> position of the adenosine molecule. These modifications enhance its receptor selectivity and binding affinity. The molecular formula of CCPA is C<sub>15</sub>H<sub>19</sub>ClN<sub>5</sub>O<sub>4</sub>, with a molecular weight of approximately 367.80 g/mol.

## Pharmacological Profile

[edit]

### Affinity and Selectivity for Adenosine Receptors

[edit]

CCPA exhibits a high binding affinity for A<sub>1</sub> adenosine receptors. In rat brain membranes, it demonstrated a K<sub>i</sub> value of 0.4 nM, indicating potent interaction. Its selectivity is underscored by a significantly lower affinity for A<sub>2A</sub> receptors, with a K<sub>i</sub> value of 3,900 nM, reflecting nearly 10,000-fold selectivity for A<sub>1</sub> over A<sub>2A</sub>.[2][3]

### Functional Effects

[edit]

As an A<sub>1</sub> receptor agonist, CCPA effectively inhibits adenylate cyclase activity. In rat adipocyte membranes, it achieved an IC<sub>50</sub> of 33 nM, demonstrating its potency. Conversely, its influence on A<sub>2A</sub> receptors is minimal, requiring much higher concentrations to elicit comparable effects.

### Interaction with A<sub>3</sub> Adenosine Receptors

[edit]

Interestingly, while CCPA acts as an agonist at A<sub>1</sub> receptors, it functions as a moderate antagonist at human A<sub>3</sub> adenosine receptors. Studies using Chinese hamster ovary cells expressing human A<sub>3</sub> receptors revealed that CCPA binds with a K<sub>i</sub> of 38 nM but does not activate the receptor. Instead, it competitively inhibits the effects of A<sub>3</sub> receptor agonists, highlighting its dual role depending on the receptor subtype.[2][4]

## Applications in Biomedical Research

[edit]

CCPA's selectivity and efficacy make it an invaluable tool in exploring adenosine receptor functions. In cardiovascular studies, it has been employed to investigate A<sub>1</sub> receptor-mediated cardioprotective mechanisms, including modulation of heart rate and ischemic responses (Ischemia). In neurological contexts, CCPA aids in elucidating the role of A<sub>1</sub> receptors in neurotransmission and neuroprotection. Additionally, its antagonistic properties at A<sub>3</sub> receptors provide insights into the complex interplay between different adenosine receptor subtypes.

2-Chloro-N<sup>6</sup>-cyclopentyladenosine (CCPA) stands out as a potent and selective adenosine A<sub>1</sub> receptor agonist with unique antagonistic effects on A<sub>3</sub> 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.

## References

[edit]

1. ^ Karl-Norbert Klotz; Martin J. Lohse; Ulrich Schwabe; Gloria Cristalli; Sauro Vittori; Mario Grifantini (1989). "2-Chloro-N6-[3H]cyclopentyladenosine ([3HCCPA) — a high affinity agonist radioligand for A1 adenosine receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 340 (6): 679–683\. doi:10.1007/BF00717744. PMID 2615857. S2CID 1114190.
2. ^ a b Gao, Zhan-guo; Jacobson, Kenneth A. (May 2002). "2-Chloro-N6-cyclopentyladenosine, adenosine A1 receptor agonist, antagonizes the adenosine A3 receptor". European Journal of Pharmacology. 443 (1–3): 39–42\. doi:10.1016/S0014-2999(02)01552-2. PMC 8358783. PMID 12044789.1–3&rft.pages=39-42&rft.date=2002-05&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358783#id-name=PMC&rft_id=info:pmid/12044789&rft_id=info:doi/10.1016/S0014-2999(02)01552-2&rft.aulast=Gao&rft.aufirst=Zhan-guo&rft.au=Jacobson,+Kenneth+A.&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358783&rfr_id=info:sid/en.wikipedia.org:CCPA+(biochemistry)" class="Z3988">
3. ^ Cristalli, Gloria; Volpini, Rosaria; Vittori, Sauro; Camaioni, Emidio; Monopoli, Angela; Conti, Annamaria; Dionisotti, Silvio; Zocchi, Cristina; Ongini, Ennio (May 1994). "2-Alkynyl Derivatives of Adenosine-5'-N-ethyluronamide: Selective A2 Adenosine Receptor Agonists with Potent Inhibitory Activity on Platelet Aggregation". Journal of Medicinal Chemistry. 37 (11): 1720–1726\. doi:10.1021/jm00037a024. ISSN 0022-2623. PMID 8201607.
4. ^ Lohse, MartinJ.; Klotz, Karl-Norbert; Schwabe, Ulrich; Cristalli, Gloria; Vittori, Sauro; Grifantini, Mario (June 1988). "2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 337 (6). doi:10.1007/BF00175797. ISSN 0028-1298.
5. ^ Fabera, Petr; Parizkova, Martina; Uttl, Libor; Vondrakova, Katerina; Kubova, Hana; Tsenov, Grygoriy; Mares, Pavel (2019-06-14). "Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats". Frontiers in Pharmacology. 10: 656. doi:10.3389/fphar.2019.00656. ISSN 1663-9812. PMC 6587156. PMID 31258477.

* v
* t
* e

Purine receptor modulators

Receptor
(ligands)|

| P0 (adenine)|

* Agonists: 8-Aminoadenine
* Adenine

|

(adenosine)|

* Agonists: 2-(1-Hexynyl)-N-methyladenosine
* 2-Cl-IB-MECA
* 2-Chloroadenosine
* 2'-MeCCPA
* 4'-O-β-D-Glucosyl-9-O-(6''-deoxysaccharosyl)olivil
* 5'-N-ethylcarboxamidoadenosine
* Adenosine
* ADP
* AMP
* Apadenoson
* ATL-146e
* ATP
* BAY 60–6583
* Binodenoson
* Capadenoson
* CCPA
* CGS-21680
* CP-532,903
* CV-1808
* Evodenoson
* GR 79236
* HENECA
* LUF-5835
* LUF-5845
* N6-Cyclopentyladenosine
* Namodenoson
* NECA
* Neladenoson dalanate
* Piclidenoson
* Regadenoson
* SDZ WAG 994
* Selodenoson
* Sonedenoson
* Tecadenoson
* Trabodenoson
* UK-432,097

* Antagonists: 3-Chlorostyrylcaffeine (CSC)
* 7-Methylxanthine
* 8-Chlorotheophylline
* 8-Phenyl-1,3-dipropylxanthine
* 8-Phenyltheophylline
* Acefylline
* Aminophylline
* ATL-444
* AZD-4635
* Bamifylline
* Cafedrine
* Caffeine
* Caffeine citrate
* Cartazolate
* CGH-2466
* CGS-15943
* Choline theophyllinate
* Ciforadenant
* CPX
* CVT-6883
* Dimethazan
* DMPX
* DPCPX
* Dyphylline
* Enprofylline
* Etazolate
* Etrumadenant
* Fenethylline
* IBMX
* Imaradenant
* Inupadenant
* ISAM-140
* ISAM-R316
* Isovaleric acid
* Istradefylline
* KF-26777
* Lu AA41063
* Lu AA47070
* MRE3008F20
* MRS-1191
* MRS-1220
* MRS-1334
* MRS-1523
* MRS-1706
* MRS-1754
* MRS-3777
* MSX-2
* MSX-3
* MSX-4
* Muvadenant
* Paraxanthine
* Pentoxifylline
* Preladenant
* Propentofylline
* Proxyphylline
* PSB-10
* PSB-11
* PSB-36
* PSB-603
* PSB-788
* PSB-1115
* PSB-1901
* Reversine
* Rolofylline
* SCH-442,416
* SCH-58261
* Sipagladenant
* Taminadenant
* Theacrine
* Theobromine
* Theodrenaline
* Theophylline
* Tozadenant
* Tracazolate
* Vipadenant
* VUF-5574
* ZM-241,385

(nucleotide)|

| P2X
(ATPTooltip Adenosine triphosphate)|

* Agonists: 2-Me-SATP
* α,β-Me-ATP
* Adenosine
* ADP
* AMP
* Ap4A
* Ap5A
* ATP
* ATPγS
* BzATP
* Cibacron blue
* CTP
* D-β,γ-Me-ATP
* GTP
* HT-AMP
* Ivermectin
* L-β,γ-Me-ATP
* MRS-2219
* PAPET-ATP
* UTP
* Zinc

* Antagonists: 5-BDBD
* A-317491
* A-438079
* A-740003
* A-804598
* A-839977
* AF-353
* AZ-10606120
* AZ-11645373
* BBG
* Calcium
* Calmidazolium
* Chelerythrine
* Copper
* Emodin (Rheum officinale)
* Evans blue
* Gefapixant
* GW-791343
* HMA
* Ip5I
* isoPPADS
* JNJ-47965567
* KN-04
* KN-62
* Magnesium
* MRS-2159
* NF-023
* NF-110
* NF-157
* NF-279
* NF-449
* Opiranserin (VVZ-149)
* Oxidized-ATP
* Phenol Red
* Phenolphthalein
* PPADS
* PPNDS
* PSB-12062
* Puerarin (Radix puerariae)
* Purotoxin 1
* RB-2
* Ro 0437626
* Ro 51
* RO-3
* Sodium ferulate (Angelica sinensis, Ligusticum wallichii)
* Suramin
* TC-P 262
* Tetramethylpyrazine (ligustrazine) (Ligusticum wallichii)
* TNP-ATP
* Zinc

|

P2Y|

* Agonists: 2-Me-SADP
* 2-Me-SATP
* 2-Thio-UTP
* 5-Br-UDP
* 5-OMe-UDP
* α,β-Me-ATP
* Adenosine
* ADP
* ADPβS
* Ap3A
* AR-C 67085MX
* ATP
* ATPγS
* CTP
* dATP
* Denufosol
* Diquafosol
* IDP
* ITP
* INS-365
* INS-37217
* MRS-2365
* MRS-2690
* MRS-2693
* MRS-2768
* MRS-2957
* MRS-4062
* NF-546
* PAPET-ATP
* PSB-0474
* PSB-1114
* UDP
* UDPβS
* UDP-galactose
* UDP-glucose
* UDP-N-acetylglucosamine
* Up3U
* UTP
* UTPγS

* Antagonists: 2-Me-SAMP
* A3P5PS
* AMPαS
* Ap4A
* AR-C 66096
* AR-C 67085MX
* AR-C 69931MX
* AR-C 118925XX
* ATP
* BzATP
* C1330-7
* Cangrelor
* Clopidogrel
* Elinogrel
* Ip5I
* MRS-2179
* MRS-2211
* MRS-2279
* MRS-2395
* MRS-2500
* MRS-2578
* NF-157
* NF-340
* PIT
* PPADS
* Prasugrel
* PSB-0739
* RB-2
* Regrelor
* Suramin
* Ticagrelor
* Ticlopidine
* UDP

Transporter
(blockers)|

| CNTsTooltip Concentrative nucleoside transporters|

* 6-Hydroxy-7-methoxyflavone
* Adenosine
* dMeThPmR
* Estradiol
* KGO-2142
* KGO-2173
* MeThPmR
* Phloridzin
* Progesterone

|

ENTsTooltip Equilibrative nucleoside transporters|

* Barbiturates
* Benzodiazepines
* Cilostazol
* Dilazep
* Dipyridamole
* Estradiol
* Ethanol
* Hexobendine
* NBMPR
* Pentoxifylline
* Progesterone
* Propentofylline

PMATTooltip Plasma membrane monoamine transporter|

* Decynium-22

Enzyme
(inhibitors)|

| XOTooltip Xanthine oxidase|

* Allopurinol
* Amflutizole
* Benzbromarone
* Caffeic acid
* Cinnamaldehyde
* Cinnamomum osmophloeum
* Febuxostat
* Myo-inositol
* Kaempferol
* Myricetin
* Niraxostat
* Oxipurinol
* Phytic acid
* Pistacia integerrima
* Propolis
* Quercetin
* Tisopurine
* Topiroxostat

|

Others|

* Aminopterin
* Azathioprine
* Methotrexate
* Mycophenolic acid
* Pemetrexed
* Pralatrexate
* Many others

Others|

* Precursors: Adenine
* Adenosine
* AMP
* ADP
* ATP
* Cytosine
* Cytidine
* CMP
* CDP
* CTP
* Guanine
* Guanosine
* GMP
* GDP
* GTP
* Hypoxanthine
* Inosine
* IMP
* IDP
* ITP
* Ribose
* Uracil
* Uridine
* UMP
* UDP
* UTP

* Others: Chrysophanol (rhubarb)

See also: Receptor/signaling modulators

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|

* v
* t
* e

*[CID]: Compound ID
*[EPA]: U.S. Environmental Protection Agency
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[ATP]: Adenosine triphosphate
*[CNTs]: Concentrative nucleoside transporters
*[ENTs]: Equilibrative nucleoside transporters
*[PMAT]: Plasma membrane monoamine transporter
*[XO]: Xanthine oxidase