6-Chloro-9-(β-D-2-deoxyribofuranosyl)purine - CAS 4594-45-0
Category:
Nucleosides
Product Name:
6-Chloro-9-(β-D-2-deoxyribofuranosyl)purine
Catalog Number:
4594-45-0
CAS Number:
4594-45-0
Molecular Weight:
270.68
Molecular Formula:
C10H11ClN4O3
COA:
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MSDS:
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Structure\Application:
2'-Deoxy-Nucleosides
Chemical Structure
CAS 4594-45-0 6-Chloro-9-(β-D-2-deoxyribofuranosyl)purine

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Reference Reading


1.Stressing the development of small molecules targeting HSP90.
Neckers L1, Trepel JB. Clin Cancer Res. 2014 Jan 15;20(2):275-7. doi: 10.1158/1078-0432.CCR-13-2571. Epub 2013 Oct 28.
Inhibitors of the molecular chaperone HSP90 have been in clinical development as anticancer agents since 1999. Recent clinical studies, including the work of Saif and colleagues in this issue of Clinical Cancer Research, demonstrate that significant progress has been made in overcoming the obstacles preventing regulatory approval.
2.Metabolism and excretion of 6-chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-ylamine, an HSP90 inhibitor, in rats and dogs and assessment of its metabolic profile in plasma of humans
Xu L1, Woodward C, Dai J, Prakash C. Drug Metab Dispos. 2013 Dec;41(12):2133-47. doi: 10.1124/dmd.113.054023. Epub 2013 Sep 17.
6-Chloro-9-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-9H-purin-2-ylamine (BIIB021), a synthetic HSP90 inhibitor, exhibited promising antitumor activity in preclinical models and was in development for the treatment of breast cancer. The metabolism and excretion of BIIB021 was investigated in rats and dogs after oral administration of [(14)C]BIIB021. The administered radioactive dose was quantitatively recovered in both species, and feces/bile was the major route of excretion. Metabolic profiling revealed that BIIB021 is extensively metabolized primarily via hydroxylation of the methyl group (M7), O-demethylation (M2), and to a lesser extent by glutathione conjugation (M8 and M9). M7 was further metabolized to form the carboxylic acid (M3) and glucuronide conjugate (M4). Human plasma obtained from the phase I study in cancer patients were also analyzed to assess the metabolism of BIIB021 in humans and to ensure that selected animal species were exposed to all human major metabolites.
3.BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation.
Wang XT1, Bao CH1, Jia YB1, Wang N1, Ma W2, Liu F3, Wang C1, Wang JB1, Song QX1, Cheng YF4. Biochem Biophys Res Commun. 2014 Oct 3;452(4):945-50. doi: 10.1016/j.bbrc.2014.09.026. Epub 2014 Sep 16.
BIIB021 is a novel, orally available inhibitor of heat shock protein 90 (Hsp90) that is currently in phase I/II clinical trials. BIIB021 induces the apoptosis of various types of tumor cells in vitro and in vivo. The aim of this study is to investigate the effect of BIIB021 on the radiosensitivity of esophageal squamous cell carcinoma (ESCC). The results indicated that BIIB021 exhibited strong antitumor activity in ESCC cell lines, either as a single agent or in combination with radiation. BIIB021 significantly downregulated radioresistant proteins including EGFR, Akt, Raf-1 of ESCC cell lines, increased apoptotic cells and enhanced G2 arrest that is more radiosensitive cell cycle phase. These results suggest that this synthetic Hsp90 inhibitor simultaneously affects multiple pathways involved in tumor development and progression in the ESCC setting and may represent a better strategy for the treatment of ESCC patients, either as a monotherapy or a radiosensitizer.
4.Stimulation of electroporation-induced inward currents in glioblastoma cell lines by the heat shock protein inhibitor AUY922.
Chiang NJ1, Wu SN, Kao CA, Huang YM, Chen LT. Clin Exp Pharmacol Physiol. 2014 Oct;41(10):830-7. doi: 10.1111/1440-1681.12273.
Membrane electroporation (MEP) increases the electrical conductivity of the plasma membrane by addition of an external electrical field. Combining MEP-induced current (IMEP ) with antineoplastic agents has been increasingly considered as a new therapeutic manoeuvre, especially in the treatment of malignant gliomas. Thus, the aim of the present study was to evaluate the effect of AUY922 (AUY), a potent inhibitor of heat-shock protein 90 (HSP90), on IMEP in glioblastoma cells. The IMEP in glioblastoma cells (U373) was generated by repetitive hyperpolarization from -80 to -200 mV. The amplitude of IMEP was increased by AUY in a concentration-dependent manner, with an EC50 of 0.32 μmol/L. In addition AUY shortened the latency to IMEP generation. Before depolarization to +50 mV, hyperpolarization to -200 mV for 50 msec produced Ca(2+) influx and subsequently increased the amplitude of the Ca(2+) -activated K(+) current (IK(Ca) ). The amplitude of IK(Ca) and Ca(2+) influx was further increased by AUY through its ability to activate IMEP .