Pentostatin

Pentostatin
Clinical data
Trade names	Nipent
AHFS/Drugs.com	Monograph
MedlinePlus	a692004
Routes of; administration	Intravenous
ATC code	L01XX08 (WHO) ;
Legal status
Legal status	CA: ℞-only; UK: POM (Prescription only); US: WARNINGRx-only;
Pharmacokinetic data
Bioavailability	n/a
Protein binding	4%
Metabolism	Hepatic, minor
Elimination half-life	2.6 to 16 hours, mean 5.7 hours
Identifiers
	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;
CAS Number	53910-25-1 ;
PubChem CID	439693;
IUPHAR/BPS	4805;
DrugBank	DB00552 ;
ChemSpider	388759 ;
UNII	395575MZO7;
KEGG	D00155 ;
ChEBI	CHEBI:27834;
ChEMBL	ChEMBL1580 ;
CompTox Dashboard (EPA)	DTXSID2023436 ;
ECHA InfoCard	100.164.991
Chemical and physical data
Formula	C11H16N4O4
Molar mass	268.273 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES n1c3c(n(c1)[C@@H]2O[C@@H]([C@@H](O)C2)CO)N\C=N/C[C@H]3O;
	InChI InChI=1S/C11H16N4O4/c16-3-8-6(17)1-9(19-8)15-5-14-10-7(18)2-12-4-13-11(10)15/h4-9,16-18H,1-3H2,(H,12,13)/t6-,7+,8+,9+/m0/s1 ; Key:FPVKHBSQESCIEP-JQCXWYLXSA-N ;
	(verify)

Pentostatin (or deoxycoformycin, trade name Nipent, manufactured by SuperGen) is an anticancer chemotherapeutic drug.^[2]

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.^[3]

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.^[4] It is given by 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.^[5]

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

Synthesis

This is the original synthetic pathway although improvements were made.

References

^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
^ Kay NE, Geyer SM, Call TG, et al. (January 2007). "Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia". Blood. 109 (2): 405–11. doi:10.1182/blood-2006-07-033274. PMC 1785105. PMID 17008537.
^ Sauter C, Lamanna N, Weiss MA (September 2008). "Pentostatin in chronic lymphocytic leukemia". Expert Opin Drug Metab Toxicol. 4 (9): 1217–22. doi:10.1517/17425255.4.9.1217. PMID 18721115.
^ Cannon T, Mobarek D, Wegge J, Tabbara IA (October 2008). "Hairy cell leukemia: current concepts". Cancer Invest. 26 (8): 860–5. doi:10.1080/07357900801965034. PMID 18798068.
^ Bolaños-Meade J, Jacobsohn DA, Margolis J, Ogden A, Wientjes MG, Byrd JC, Lucas DM, Anders V, Phelps M, Grever MR, Vogelsang GB (April 2005). "Pentostatin in steroid-refractory acute graft-versus-host disease". J Clin Oncol. 23 (12): 2661–8. doi:10.1200/JCO.2005.06.130. PMID 15837980.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ Kusakabe Hitoshi & Kodama Kenjirou (+4), JPS52128292 (1977-10-27 to Yamasa Shoyu Kk); CA, 88,73015
^ GB2005661 idem David C. Baker & Sterling R. Putt, US4117229 (1978 to Warner Lambert Co LLC).
^ David C. Baker & Sterling R. Putt, US4195176 (1980 to Warner Lambert Co LLC).
^ Pasit Phiasivongsa, Sanjeev Redkar, WO2005027838 (2005 to Supergen, Inc.).
^ Oleksandr Zabudkin, Christian Schickaneder, Iaroslav Matviienko, Volodymyr Sypchenko, WO2017005784 (2017 to Synbias Pharma Ag).

This antineoplastic or immunomodulatory drug article is a stub. You can help Wikipedia by expanding it.

[FDA-AllBoxedWarnings-1] "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.

[pmid17008537-2] Kay NE, Geyer SM, Call TG, et al. (January 2007). "Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia". Blood. 109 (2): 405–11. doi:10.1182/blood-2006-07-033274. PMC 1785105. PMID 17008537.

[pmid18721115-3] Sauter C, Lamanna N, Weiss MA (September 2008). "Pentostatin in chronic lymphocytic leukemia". Expert Opin Drug Metab Toxicol. 4 (9): 1217–22. doi:10.1517/17425255.4.9.1217. PMID 18721115.

[pmid18798068-4] Cannon T, Mobarek D, Wegge J, Tabbara IA (October 2008). "Hairy cell leukemia: current concepts". Cancer Invest. 26 (8): 860–5. doi:10.1080/07357900801965034. PMID 18798068.

[PMID15837980-5] Bolaños-Meade J, Jacobsohn DA, Margolis J, Ogden A, Wientjes MG, Byrd JC, Lucas DM, Anders V, Phelps M, Grever MR, Vogelsang GB (April 2005). "Pentostatin in steroid-refractory acute graft-versus-host disease". J Clin Oncol. 23 (12): 2661–8. doi:10.1200/JCO.2005.06.130. PMID 15837980.

[6] 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.

[7] 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.

[8] 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.

[9] 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.

[10] 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.

[11] Kusakabe Hitoshi & Kodama Kenjirou (+4), JPS52128292 (1977-10-27 to Yamasa Shoyu Kk); CA, 88,73015

[12] GB2005661 idem David C. Baker & Sterling R. Putt, US4117229 (1978 to Warner Lambert Co LLC).

[13] David C. Baker & Sterling R. Putt, US4195176 (1980 to Warner Lambert Co LLC).

[14] Pasit Phiasivongsa, Sanjeev Redkar, WO2005027838 (2005 to Supergen, Inc.).

[15] Oleksandr Zabudkin, Christian Schickaneder, Iaroslav Matviienko, Volodymyr Sypchenko, WO2017005784 (2017 to Synbias Pharma Ag).

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