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Drug-Target Interaction

Drug

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PubChem ID:97297
Structure:
Synonyms:
(2R,3R,4S,5R)-2-(4-AMINO-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-(HYDROX
(2R,3R,4S,5R)-2-(4-AMINO-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-(HYDROXYMETHYL)TETRAHYDROFURAN-3,4-DIOL
(2R,3R,4S,5R)-2-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol
2-(4-Amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-5-hydroxymethyl-tetrahydro-furan-3,4-diol
24386-93-4
5-iodo-7-(beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine
5-Iodotubercidin
5ID
7-iodo-7-deazaadenosine
7-iodotubercidin
7H-Pyrrolo(2,3-d)pyrimidin-4-amine, 5-iodo-7-beta-D-ribofuranosyl-
AIDS-187690
AIDS187690
Ambap3549
CHEBI:40167
DB04604
LS-186784
LS-187457
NSC 113939

Target

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Uniprot ID:KAPCA_HUMAN
Synonyms:
cAMP-dependent protein kinase catalytic subunit alpha
PKA C-alpha
EC-Numbers:2.7.11.11
Organism:Homo sapiens
Human
PDB IDs:2GU8
Structure:
2GU8

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

12522004
Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes.. Clara Campŕs; José Manuel Lopez; Antonio F Santidrián; Montserrat Barragán; Beatriz Bellosillo; Dolors Colomer; Joan Gil (2003) Blood display abstract
Acadesine, 5-aminoimidazole-4-carboxamide (AICA) riboside, induced apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells in all samples tested (n = 70). The half-maximal effective concentration (EC(50)) for B-CLL cells was 380 +/- 60 microM (n = 5). The caspase inhibitor Z-VAD.fmk completely blocked acadesine-induced apoptosis, which involved the activation of caspase-3, -8, and -9 and cytochrome c release. Incubation of B-CLL cells with acadesine induced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), indicating that it is activated by acadesine. Nitrobenzylthioinosine (NBTI), a nucleoside transport inhibitor, 5-iodotubercidin, an inhibitor of adenosine kinase, and adenosine completely inhibited acadesine-induced apoptosis and AMPK phosphorylation, demonstrating that incorporation of acadesine into the cell and its subsequent phosphorylation to AICA ribotide (ZMP) are necessary to induce apoptosis. Inhibitors of protein kinase A and mitogen-activated protein kinases did not protect from acadesine-induced apoptosis in B-CLL cells. Moreover, acadesine had no effect on p53 levels or phosphorylation, suggesting a p53-independent mechanism in apoptosis triggering. Normal B lymphocytes were as sensitive as B-CLL cells to acadesine-induced apoptosis. However, T cells from patients with B-CLL were only slightly affected by acadesine at doses up to 4 mM. AMPK phosphorylation did not occur in T cells treated with acadesine. Intracellular levels of ZMP were higher in B-CLL cells than in T cells when both were treated with 0.5 mM acadesine, suggesting that ZMP accumulation is necessary to activate AMPK and induce apoptosis. These results suggest a new pathway involving AMPK in the control of apoptosis in B-CLL cells and raise the possibility of using acadesine in B-CLL treatment.