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Identification
Name Pentostatin
Accession Number DB00552 (APRD00202)
Type small molecule
Groups approved
Description

A potent inhibitor of adenosine deaminase. The drug is effective in the treatment of many lymphoproliferative malignancies, particularly hairy-cell leukemia. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
2'-DCF
2'-Deoxycoformycin
2'-Dexoycoformycin
Deoxycoformycin
Salts Not Available
Brand names
Name Company
Co-V
Co-Vidarabine
Covidarabine
Nipent
PD-ADI
Vidarbine
Vira a Deaminase Inhibitor
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Antibiotics
CAS number 53910-25-1
Weight Average: 268.2691
Monoisotopic: 268.11715502
Chemical Formula C11H16N4O4
InChI Key InChIKey=FPVKHBSQESCIEP-JQCXWYLXSA-N
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
Plain Text
IUPAC Name
(8R)-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H,6H,7H,8H-imidazo[4,5-d][1,3]diazepin-8-ol
SMILES
OC[C@H]1O[C@H](C[C@@H]1O)N1C=NC2=C1N=CNC[C@H]2O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Glycerol and Derivatives
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Carboxylic Acids and Derivatives
  • Ethers
  • Alcohols and Polyols
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Furans
  • Imines
  • Cyanamides
Pharmacology
Indication For the treatment of hairy cell leukaemia refractory to alpha interferon.
Pharmacodynamics Pentostatin is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia and hairy cell leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase).
Mechanism of action Pentostatin is a potent transition state inhibitor of adenosine deaminase (ADA), the greatest activity of which is found in cells of the lymphoid system. T-cells have higher ADA activity than B-cells, and T-cell malignancies have higher activity than B-cell malignancies. The cytotoxicity that results from prevention of catabolism of adenosine or deoxyadenosine is thought to be due to elevated intracellular levels of dATP, which can block DNA synthesis through inhibition of ribonucleotide reductase. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase).
Absorption Not absorbed orally, crosses blood brain barrier.
Volume of distribution Not Available
Protein binding 4%
Metabolism Primarily hepatic, but only small amounts are metabolized.
Route of elimination In man, following a single dose of 4 mg/m2 of pentostatin infused over 5 minutes, approximately 90% of the dose was excreted in the urine as unchanged pentostatin and/or metabolites as measured by adenosine deaminase inhibitory activity.
Half life 5.7 hours (with a range between 2.6 and 16 hrs)
Clearance
  • 68 mL/min/m2
Toxicity LD50=128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and myelosuppression.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Hospira inc
  • Bedford laboratories
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
Pentostatin 10 mg vial 2280.0 USD vial
Nipent 10 mg vial 1891.31 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 220 °C PhysProp
water solubility 30 mg/mL Not Available
logP -1.1 Not Available
pKa 5.2 MERCK INDEX (1996)
Predicted Properties
Property Value Source
water solubility 1.07e+01 g/l ALOGPS
logP -2 ALOGPS
logP -2 ChemAxon
logS -1.4 ALOGPS
pKa (strongest acidic) 13.06 ChemAxon
pKa (strongest basic) 8.33 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 112.13 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 64.98 ChemAxon
polarizability 26.44 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Link
External Links
Resource Link
KEGG Drug D00155 Link_out
KEGG Compound C02267 Link_out
PubChem Compound 439693 Link_out
PubChem Substance 46507116 Link_out
ChemSpider 37371 Link_out
BindingDB 50003603 Link_out
Therapeutic Targets Database DAP000566 Link_out
PharmGKB PA450863 Link_out
Drug Product Database 2011247 Link_out
Drugs.com http://www.drugs.com/cdi/pentostatin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Pentostatin Link_out
ATC Codes
  • L01XX08
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (56.7 KB)
Interactions
Drug Interactions
Drug Interaction
Cyclophosphamide Increased toxicity of cyclophosphamide
Fludarabine Unacceptable pulmonary toxicity
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available
Targets

1. Adenosine deaminase

Pharmacological action: yes
Actions: inhibitor

Adenosine + H(2)O = inosine + NH(3)

Organism class: human
UniProt ID: P00813 Link_out
Gene: ADA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Jackson RC, Leopold WR, Ross DA: The biochemical pharmacology of (2’-R)-chloropentostatin, a novel inhibitor of adenosine deaminase. Adv Enzyme Regul. 1986;25:125-39. Pubmed
  3. Newman DJ, Cragg GM: Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20. Pubmed
  4. Cabanillas F: Purine nucleoside analogs in indolent non-Hodgkin’s lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19