Pentostatin

Pentostatin is an irreversible inhibitor of adenosine deaminase with Ki of 2.5 pM.

A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.

Large-scale production is prepared by immersing or deep culturing Streptomyces and tibioticus, the bacteria that produce pentostatin: 1. Fermentation The selected culture medium is implanted with sterilized water-soluble nutrient solution, under sterile conditions, at 20 ~ 45 ℃ is preferably 33 ~ 40 ℃), aeration and stirring culture, until pentostatin appears in the culture solution. Factors affecting the length of time to obtain the maximum yield are the type and size of equipment used, the speed of agitation, the speed of aeration, microbial culture medium and other factors. Large-scale industrial fermentation in a tank-shaped fermentor can be performed for 3 to 7 days to obtain the maximum yield. A shorter fermentation time can also be used, but the yield is lower. When fermentation is performed in a shaker flask, the time required is longer than with a large-volume fermentor. When immersed in culture, microorganisms grow into discrete particles distributed throughout the nutrient solution; while on the surface, a continuous film is formed on the surface of the nutrient solution. Because the microorganisms are distributed in the entire nutrient solution, a large volume of inoculation nutrient solution can be used when the tanks and tanks used in the fermentation industry are used for microorganism cultivation. A continuous-cylinder fermenter equipped with stirring and aeration devices is particularly suitable for large-scale production, but other fermentation equipment can also be used. When producing or preparing a microbial culture medium for large-scale fermentation in a small amount, immersion culture can be carried out in a small flask, which can be shaken or stirred using a suitable method. When immersed in culture, aeration and stirring of the culture solution can be accomplished in many ways. Stirring can be achieved by other mechanical stirring equipment such as turbines, paddle stirrers, impeller propellers, etc., or it can be rotated or oscillated by the fermenter itself, or by using various pump equipment to inject air or oxygen into the nutrient solution. Inflation can use an open tube, a porous tube or a tube with a dispenser to inject air or oxygen, or the nutrient solution can be sprayed, splashed or spilled into the oxygen atmosphere. Another option for immersion outside of culture is surface culture. At this time, a thin layer of sterilized water-soluble culture liquid of 2 cm or less was used to implant Streptomyces antibioticus, which produces pentostein, and cultured at 20-45°C under oxygenation. Available products are similar to immersion culture. 2. Separation and purification separation can use pressure filtration or centrifugal separation. The filter cake was washed thoroughly with water. After the washing liquid and the filtrate were combined, the Ph value was adjusted to about 9.2 with an alkaline aqueous solution such as sodium hydroxide, triethylamine or ammonium hydroxide. Concentrate under reduced pressure to about 1/10 volume remaining. The concentrated solution is cooled to 5℃, and the time can be several hours or several days (depending on the volume). The precipitate that precipitated out was 9-(β-D-arabinose furanosyl) adenine, which can be removed by filtration using celite as a filter aid. The filtrate was diluted with water to the volume before concentration, and then adjusted to pH 8.3 with water-soluble acids such as hydrochloric acid or sulfuric acid. Use activated carbon or other adsorbent (preferably Darco G-60) for adsorption. The adsorption process can be carried out in batches or continuously through the column. In the batch method, 0.5% to 10%, preferably about 3% (W/V) of activated carbon is added to the filtrate and stirred for 1 to 3 hours. After filtration, the filter cake was washed with water and then eluted with an aqueous acetone solution (equal acetone and water). The eluent is concentrated to a volume of about 1% to 3%. Methanol was added to the concentrate to obtain an 80% methanol solution. The resulting precipitate was removed by filtration, and the filtrate was concentrated to remove methanol. The concentrate was diluted with 5% acetone in water to 2.5 times its volume and passed through an activated carbon column. The activated carbon column was first washed with 5% acetone aqueous solution and then with 10% acetone aqueous solution. It was then eluted with 25% aqueous acetone. The eluate was concentrated under reduced pressure and lyophilized. The dried solid was dissolved in a small amount of water, and diafiltered through a column containing Sephadex G-10 prepared with water. Wash the column with water, collect the effluent containing the product, dry, and crystallize with methanol aqueous solution to obtain penastatin

An adenosine deaminase inhibitor used as an anti-cancer therapeutic drug.Shown to be effective in the treatment of hairy cell leukemia as well as having use in the treatment of other types of cancer such as chronic lymphocytic leukemia.

Molecular Weight:268.27
XLogP3:-2.1
Hydrogen Bond Donor Count:4
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:2
Exact Mass:268.11715500
Monoisotopic Mass:268.11715500
Topological Polar Surface Area:112
Heavy Atom Count:19
Complexity:356
Undefined Atom Stereocenter Count:4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes