Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Pentostatin: Difference between pages

{{Short description|Chemical compound}}

| Watchedfields = changed

| verifiedrevid = 464198455

| IUPAC_name = (R)-3-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol

| image = Pentostatin structure.svg

| image2 = Pentostatin ball-and-stick.png

| width2 = 200

| pregnancy_US = D

| legal_CA = Rx-only

| legal_UK = POM

| IUPHAR_ligand = 4805

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| ChEBI = 27834

| C=11 | H=16 | N=4 | O=4

'''Pentostatin''' (or '''deoxycoformycin''', trade name '''Nipent''', manufactured by SuperGen) is an anticancer [[chemotherapeutic]] drug.<ref name="pmid17008537">{{cite journal |vauthors=Kay NE, Geyer SM, Call TG, etal |title=Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia |journal=Blood |volume=109 |issue=2 |pages=405–11 |date=January 2007 |pmid=17008537 |pmc=1785105 |doi=10.1182/blood-2006-07-033274 |url=}}</ref>

==Mechanism==

It is classified as a [[purine analog]], which is a type of [[antimetabolite]].

It mimics the [[nucleoside]] [[adenosine]] and thus inhibits the enzyme [[adenosine deaminase]], interfering with the cell's ability to process DNA.<ref name="pmid18721115">{{cite journal |vauthors=Sauter C, Lamanna N, Weiss MA |title=Pentostatin in chronic lymphocytic leukemia |journal=Expert Opin Drug Metab Toxicol |volume=4 |issue=9 |pages=1217–22 |date=September 2008 |pmid=18721115 |doi=10.1517/17425255.4.9.1217 }}</ref>

[[Cancer]] cells generally divide more often than healthy cells; DNA is highly involved in cell division ([[mitosis]]) and drugs which target DNA-related processes are therefore more toxic to cancer cells than healthy cells.

==Uses==

Pentostatin is used to treat [[hairy cell leukemia]].<ref name="pmid18798068">{{cite journal |vauthors=Cannon T, Mobarek D, Wegge J, Tabbara IA |title=Hairy cell leukemia: current concepts |journal=Cancer Invest. |volume=26 |issue=8 |pages=860–5 |date=October 2008 |pmid=18798068 |doi=10.1080/07357900801965034 }}</ref> It is given by [[Intravenous therapy|intravenous]] infusion once every two weeks for three to six months.

Additionally, pentostatin has been used to treat steroid-refractory acute and chronic [[graft-versus-host disease]].<ref name="PMID15837980">{{cite journal |vauthors=Bolaños-Meade J, Jacobsohn DA, Margolis J, Ogden A, Wientjes MG, Byrd JC, Lucas DM, Anders V, Phelps M, Grever MR, Vogelsang GB |title=Pentostatin in steroid-refractory acute graft-versus-host disease |journal=J Clin Oncol |volume=23 |issue=12 |pages=2661–8 |date=April 2005 |pmid=15837980 |doi=10.1200/JCO.2005.06.130|doi-access=free }}</ref>

Pentostatin is also used in [[chronic lymphocytic leukemia]] (CLL) patients who have relapsed.

==Synthesis==

This is the original synthetic pathway although improvements were made.

[[File:Pentostatin synthesis.svg|thumb|center|500px|[https://www.chemdrug.com/article/8/3284/16419621.html ChemDrug] Original synthesis:<ref>Baker, D. C., Putt, S. R. (September 1979). "A total synthesis of pentostatin, the potent inhibitor of adenosine deaminase". Journal of the American Chemical Society. 101 (20): 6127–6128. doi:10.1021/ja00514a048.</ref><ref>Showalter, H.D.Hollis; Putt, Sterling R (1981). "Studies related to the total synthesis of pentostatin: An efficient, regiospecific glycosylation of 6,7-dihydroimidazo[4,5-d][1,2]diazepin-8(3H)-one and related homologs.". Tetrahedron Letters. 22 (33): 3155–3158. doi:10.1016/S0040-4039(01)81851-7.</ref><ref>Chan, Eunice; Putt, Sterling R.; Showalter, H. D. Hollis; Baker, David C. (1982). "Total synthesis of (8R)-3-(2-deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol (pentostatin), the potent inhibitor of adenosine deaminase". The Journal of Organic Chemistry. 47 (18): 3457–3464. doi:10.1021/jo00139a015.</ref><ref>Baker, David C.; Putt, Sterling R.; Showalter, H. D. Hollis (1983). "Studies related to the total synthesis of pentostatin. Approaches to the synthesis of (8R)-3,6,7,8-tetrahydroimidazo-[4,5-d][1,3]diazepin-8-ol andN-3 alkyl congeners". Journal of Heterocyclic Chemistry. 20 (3): 629–634. doi:10.1002/jhet.5570200324.</ref><ref>Tunac, J. B.; Underhill, M. (1985). "2'-Chloropentostatin: Discovery, fermentation and biological activity.". The Journal of Antibiotics. 38 (10): 1344–1349. doi:10.7164/antibiotics.38.1344.</ref> Patents:<ref>Kusakabe Hitoshi & Kodama Kenjirou (+4), JPS52128292 (1977-10-27 to Yamasa Shoyu Kk); CA, 88,73015</ref><ref>GB2005661 idem David C. Baker & Sterling R. Putt, US4117229 (1978 to Warner Lambert Co LLC).</ref><ref>David C. Baker & Sterling R. Putt, US4195176 (1980 to Warner Lambert Co LLC).</ref><ref>Pasit Phiasivongsa, Sanjeev Redkar, WO2005027838 (2005 to Supergen, Inc.).</ref><ref>Oleksandr Zabudkin, Christian Schickaneder, Iaroslav Matviienko, Volodymyr Sypchenko, WO2017005784 (2017 to Synbias Pharma Ag).</ref>]]

==References==

{{reflist}}

{{Chemotherapeutic agents}}

[[Category:Nucleosides]]

[[Category:Purine antagonists]]

[[Category:Adenosine deaminase inhibitors]]

{{antineoplastic-drug-stub}}