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Drug-Target Interaction

Drug

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PubChem ID:160355
Structure:
Synonyms:
"insolution™ roscovitine"
(2r)-2-{[6-(benzylamino)-9-isopropyl-9h-purin-2-yl]amino}-1-butanol
(R)-Roscovitine
1-Butanol,
1-Butanol, 2-((9-(1-methylethyl)-6-((phenylmethyl)amino)-9H-purin-2- yl)amino)-, (2R)-
1-Butanol, 2-((9-(1-methylethyl)-6-((phenylmethyl)amino)-9H-purin-2- yl)amino)-, (2R)-
1-Butanol, 2-((9-(1-methylethyl)-6-((phenylmethyl)amino)-9H-purin-2- yl)amino)-, (R)-
1-Butanol, 2-[[9-(1-methylethyl)-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-, (2R)-
186692-46-6
2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine
2-(R)-[[9-(1-Methylethyl)-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-1-butanol
2-[[9-(1-Methylethyl)-6-[(phenylmethyl)amino]- 9H-purin-2-yl]amino]-(R)-1-butanol
2a4l
3ddq
6-(Benzylamino)-2(R)-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine
AIDS-022527
AIDS022527
BCBcMAP01_000013
Bio1_000302
Bio1_000791
Bio1_001280
Bio2_000379
Bio2_000859
BiomolKI2_000054
BiomolKI_000048
BSPBio_001078
CBiol_002016
CYC 202
CYC-202
CYC202
CYC202, Seliciclib, R-roscovitine, Roscovitine
HSCI1_000092
IDI1_002134
InSolution™ Roscovitine
K00020
KBio2_000418
KBio2_002986
KBio2_005554
KBio3_000795
KBio3_000796
KBioGR_000418
KBioSS_000418
Lopac0_001102
LS-182554
NCGC00094374-01
NCGC00094374-02
NCGC00094374-03
NCGC00094374-04
NCI60_036420
NSC 701554
NSC-701554
NSC701554
R-Roscovitine
R7772_SIGMA
Rosco
Roscovitine
RRC
Seliciclib
SMP1_000266
ZINC01649340

Target

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Uniprot ID:ICE_DROME
Synonyms:
Caspase
drICE
EC-Numbers:3.4.22.-
Organism:Drosophila melanogaster
Fruit fly
PDB IDs:-

Binding Affinities:

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

10871858
Cdk inhibitors, roscovitine and olomoucine, synergize with farnesyltransferase inhibitor (FTI) to induce efficient apoptosis of human cancer cell lines.. H Edamatsu; C L Gau; T Nemoto; L Guo; F Tamanoi (2000) Oncogene display abstract
Farnesyltransferase inhibitor (FTI) induces apoptosis of transformed cells. This involves changes in mitochondria, including decrease of mitochondrial membrane potential and the release of cytochrome c. The released cytochrome c then induces events leading to the activation of caspase-3. In this study, we report that purine derivative cyclin-dependent kinase (Cdk) inhibitors, roscovitine and olomoucine, dramatically enhance this FTI-induced apoptosis of human cancer cell lines. We noticed the synergy between Cdk inhibitors and FTI through our screen to identify compounds that enhance FTI-induced apoptosis of promyelocytic leukemic cell line HL-60. The Cdk inhibitors by themselves do not induce apoptosis at the concentrations used. Roscovitine synergizes with FTI to release cytochrome c from mitochondria. In addition, we detected synergistic effects of FTI and roscovitine to inhibit hyperphosphorylation of retinoblastoma protein. Enhancement of FTI-induced apoptosis by roscovitine is not unique to HL-60 cells, since similar synergy was observed with a leukemic cell line CEM and a prostate cancer cell line LNCaP. In LNCaP cells, in addition to roscovitine and olomoucine, phophatidylinositol 3-kinase (PI 3-kinase) inhibitor, LY294002, was effective in enhancing FTI-induced apoptosis. However, the effects of roscovitine appear to be distinct from those of LY294002, since roscovitine did not affect Akt activity while LY294002 significantly decreased the activity of Akt. Our finding of the synergy between FTI and Cdk inhibitor is significant for understanding the mechanism of action of FTI as well as for clinical use of FTI.
12845642
Rapid onset of nucleolar disintegration preceding cell cycle arrest in roscovitine-induced apoptosis of human MCF-7 breast cancer cells.. Jacek Wojciechowski; Marcel Horky; Marieta Gueorguieva; Jˇzefa Wesierska-Gadek (2003) International journal of cancer. Journal international du cancer display abstract
The aim of our study was to explore the antiproliferative and pro-apoptotic action of roscovitine (ROSC) on human breast cancer MCF-7 cells. We examined the effect of ROSC on cell proliferation, cell cycle progression, nucleolar morphology, posttranslational modifications of histones as well as on induction of apoptosis. The effects of ROSC on the argyrophilic nucleolar organizer regions (AgNORs) and nucleolar RNA of MCF-7 cells were marked: ROSC treatment changed the pattern of AgNORs in a time-dependent manner. The disintegration of nucleoli manifested by increasing number of nucleolar fragments already began at 6 hr posttreatment. This was accompanied by a redistribution of the nucleolin from the nucleolus beginning after 6 hr and preceded a decrease of histone acetylation and phosphorylation. Inhibition of DNA synthesis and accumulation of G(2)/M-arrested cells starting 6 hr posttreatment coincided with a strong increase of the p53 level and with an appearance of a few cells committed to undergo apoptosis. However, all these changes preceded the main wave of apoptosis, which occurred after 24 hr ROSC treatment as assessed by determination of the frequency of Annexin binding, activation of caspases as well as of DNA fragmentation. Onset of PARP-1 cleavage detected by immunoblotting and by immunohistochemistry 6 hr or 9 hr posttreatment, respectively, preceded for a few hours the DNA fragmentation detected in situ by TUNEL assay. Reconstitution of MCF-7 cells with caspase-3 did not change the kinetics of ROSC-induced apoptosis. Our results show that disintegration of nucleoli is an early marker of ROSC-induced changes. Cell cycle arrest precedes the main wave of apoptosis.