16506-88-0

Usage

Uses

Used in Cancer Treatment:
Gemcitabine is used as a chemotherapy agent for the treatment of various types of cancer, including pancreatic, lung, breast, and ovarian cancer. It works by disrupting the synthesis of DNA and RNA in cancer cells, ultimately leading to their destruction. This makes it a valuable tool in the fight against cancer, as it can effectively target and eliminate cancer cells.
Used in Combination Therapy:
Gemcitabine is often used in combination with other chemotherapy drugs to enhance its effectiveness. This combination therapy can improve the overall treatment outcome for cancer patients, as it allows for a more comprehensive attack on the cancer cells. The use of gemcitabine in combination with other drugs can also help to reduce the likelihood of drug resistance, which is a common challenge in cancer treatment.
Used in Pharmaceutical Research:
As a nucleoside analog, gemcitabine is also used in pharmaceutical research to better understand the mechanisms of cancer cell growth and the development of new cancer treatments. Its unique properties and effectiveness in disrupting DNA and RNA synthesis make it an important compound for studying the molecular basis of cancer and identifying potential targets for new therapeutic agents.

InChI:InChI=1/C10H14ClN5O10P2/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(18)5(17)3(25-9)1-24-28(22,23)26-27(19,20)21/h2-3,5-6,9,17-18H,1H2,(H,22,23)(H2,12,14,15)(H2,19,20,21)/t3-,5-,6-,9-/m1/s1

Upstream product

• 21466-01-3 phosphoric acid mono[(2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-ylmethyl]ester 
• 49564-60-5 2-chloro-adenosine-5'-triphosphate 

Relevant academic research and scientific papers

Hydrolysis of P2-purinoceptor agonists by a purified ectonucleotidase from the bovine aorta, the ATP-diphosphohydrolase.

Pharmacologists are becoming more and more aware of the possibility that certain ATP analogues currently used to classify the P2-purinoceptors are dephosphorylated by ectonucleotidases. In this study, we provide evidence that in the vascular system, these purine analogues are hydrolysed by an ATP-diphosphohydrolase (ATPDase). This enzyme is known as the major plasma membrane nucleotidase of endothelial and smooth muscle cells, and is believed to dephosphorylate extracellular triphospho- and diphosphonucleosides. Assays were conducted with a purified ATPDase from smooth muscle cells of bovine aorta. At a concentration of 250 microM, adenosine 5'-(alpha,beta-methylene) triphosphonate (alpha,beta-metATP), adenosine 5'-(beta,gamma-methylene) triphosphonate (beta,gamma-metATP), adenosine 5'-(alpha,beta-methylene) disphosphonate (alpha,beta-metADP), adenylyl 5'-(beta,gamma-imido) diphosphonate (beta,gamma-imidoATP) and adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) all resisted dephosphorylation, whereas 2-chloroadenosine triphosphate (2-chloroATP), 2-methylthioadenosine triphosphate (2-MeSATP) and 8-bromoadenosine triphosphate (8-bromo-ATP) were hydrolysed at 99, 63, and 20% of the rate of ATP hydrolysis, respectively. All the non-hydrolysable analogues tested, except alpha,beta-metADP, competed with ATP and ADP for the ATPDase catalytic site, reducing their hydrolysis by 35-50%. Apparent Km values for ATP and ADP were estimated at 14.1 and 12.0 microM, respectively, whereas apparent Km and Ki values for the purine analogues ranged from 12 to 28 microM. These results strongly support the view that (1) the ATPDase is expected to reduce substantially the P2-response induced by ATP, ADP, and some hydrolysable agonists; and (2) by competing with the hydrolysis of endogenously released ATP and ADP, non-hydrolysable analogues could alter the amplitude or direction of the cellular response induced by these natural substrates.

2-ClATP exerts anti-tumoural actions not mediated by P2 receptors in neuronal and glial cell lines

We investigated the effects of the ATP analogue and P2 receptor agonist 2-ClATP on growth and survival of different neuronal (PC12, PC12nnr5 and SH-SY5Y) and glial (U87 and U373) cell lines, by the use of direct count of intact nuclei, fluorescence microscopy, fluorescence-activated cell sorter analysis (FACS) and high pressure liquid chromatography (HPLC). 2-ClATP lowered the number of cultured PC12nnr5, SH-SY5Y, U87 and U373 cells to almost 5%, and of PC12 cells to about 35% after 3-4 days of treatment. EC50 was in the 5-25μM range, with 2-ClATP behaving as a cytotoxic or cytostatic agent. Analysis of the biological mechanisms demonstrated that pyridoxalphosphate-6- azophenyl-2′,4′-disulphonic acid (P2 receptor antagonist and nucleotidases inhibitor), but not Caffeine or CGS-15493 (P1 receptor antagonists) effectively prevented 2-ClATP-induced toxicity. 2-ClATP metabolic products (2-ClADP, 2-ClAMP, 2-Cladenosine) and new synthesis derivatives (2-CldAMP, 2-Cldadenosine-3′,5′-bisphosphate and 2-CldATP) exerted similar cytotoxic actions. Inhibition of both serum nucleotidases and purine nucleoside transporters strongly reduced 2-ClATP-induced cell death, which was conversely increased by the nucleotide hydrolyzing enzyme apyrase. The adenosine kinase inhibitor 5-iodotubericidin totally prevented 2-ClATP or 2-Cladenosine-induced toxicity. In summary, our findings indicate that 2-ClATP exerts either cell cycle arrest or cell death, acting neither on P2 nor on P1 receptors, but being extracellularly metabolized into 2-Cladenosine, intracellularly transported and re-phosphorylated.