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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2019-07-23 06:00:21 UTC
HMDB IDHMDB0014692
Secondary Accession Numbers
  • HMDB14692
Metabolite Identification
Common NamePentostatin
DescriptionPentostatin is only found in individuals that have used or taken this drug. It is 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]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).
Structure
Data?1563861621
Synonyms
ValueSource
NipentKegg
2'-DCFHMDB
2'-DeoxycoformycinHMDB
2'-DexoycoformycinHMDB
DeoxycoformycinHMDB
CO-VidarabineMeSH
Lederle brand OF pentostatinMeSH
Warner-lambert brand OF pentostatinMeSH
Prasfarma brand OF pentostatinMeSH
2' DeoxycoformycinMeSH
co VidarabineMeSH
Supergen brand OF pentostatinMeSH
Wyeth brand OF pentostatinMeSH
Chemical FormulaC11H16N4O4
Average Molecular Weight268.2691
Monoisotopic Molecular Weight268.11715502
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
Traditional Namepentostatin
CAS Registry Number53910-25-1
SMILES
OC[C@H]1O[C@H](C[C@@H]1O)N1C=NC2=C1N=CNC[C@H]2O
InChI Identifier
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
InChI KeyFPVKHBSQESCIEP-JQCXWYLXSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as imidazodiazepines. These are organic compounds containing an imidazole ring fused to a diazepine ring. Imidazole is 5-membered ring consisting of three carbon atoms, and two nitrogen centers at the 1- and 3-positions. Diazepine is a 7-membered ring consisting of five carbon and two nitrogen atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazodiazepines
Sub ClassNot Available
Direct ParentImidazodiazepines
Alternative Parents
Substituents
  • Imidazo-meta-diazepine
  • Imidazodiazepine
  • Meta-diazepine
  • N-substituted imidazole
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Tetrahydrofuran
  • Secondary alcohol
  • Amidine
  • Formamidine
  • Carboxylic acid amidine
  • Oxacycle
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Primary alcohol
  • Alcohol
  • Organic nitrogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point220 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility10.7 g/LNot Available
LogP-1.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility10.7 g/LALOGPS
logP-2ALOGPS
logP-2ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)13.06ChemAxon
pKa (Strongest Basic)8.33ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area112.13 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity64.98 m³·mol⁻¹ChemAxon
Polarizability26.44 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000f-9280000000-53989a5cd0535c5bb1c0JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-0g4i-5556900000-faa1467da14d5869f1a4JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udr-0920000000-59e330d7bf2bc1680990JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udr-0900000000-e3af78d60d01def1ac1aJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0f79-1900000000-d626d4471ad700c9f0d6JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0390000000-b18e6406ad078d5394a4JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0910000000-bc5d8c218c955e8890bdJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05ai-9400000000-3516f2a449bec4f6eab1JSpectraViewer | MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00552 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00552 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00552
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID388759
KEGG Compound IDC02267
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPentostatin
METLIN IDNot Available
PubChem Compound439693
PDB IDDCF
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Mercieca J, Matutes E, Moskovic E, MacLennan K, Matthey F, Costello C, Behrens J, Basu S, Roath S, Fairhead S, et al.: Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases. Br J Haematol. 1992 Nov;82(3):547-54. [PubMed:1283078 ]
  2. Schwartz CL, Minniti CP, Harwood P, Na S, Banquerigo ML, Strauss LC, Kurtzberg J, Smith SD, Civin CI: Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin. J Clin Oncol. 1987 Dec;5(12):1900-11. [PubMed:3500279 ]
  3. Thaler J, Denz H, Dietze O, Gastl G, Ho AD, Gattringer C, Greil R, Lechleitner M, Huber C, Huber H: Immunohistological assessment of bone marrow biopsies from patients with hairy cell leukemia: changes following treatment with alpha-2-interferon and deoxycoformycin. Leuk Res. 1989;13(5):377-83. [PubMed:2787447 ]
  4. Ruers TJ, Buurman WA, van der Linden CJ: 2'Deoxycoformycin and deoxyadenosine affect IL 2 production and IL 2 receptor expression of human T cells. J Immunol. 1987 Jan 1;138(1):116-22. [PubMed:3097141 ]
  5. Lembersky BC, Golomb HM: Hairy cell leukemia: clinical features and therapeutic advances. Cancer Metastasis Rev. 1987;6(3):283-300. [PubMed:2446791 ]
  6. Sainati L, Matutes E, Mulligan S, de Oliveira MP, Rani S, Lampert IA, Catovsky D: A variant form of hairy cell leukemia resistant to alpha-interferon: clinical and phenotypic characteristics of 17 patients. Blood. 1990 Jul 1;76(1):157-62. [PubMed:2364167 ]
  7. Okamura K, Ikeda T, Shimakura Y, Yoshiba F, Kishi K, Ando K, Hotta T: [Allogeneic bone marrow transplantation for chemotherapy-resistant T-prolymphocytic leukemia]. Rinsho Ketsueki. 2005 Jul;46(7):527-31. [PubMed:16440747 ]
  8. Mughal TI, Goldman JM: Chronic leukaemias: can they be cured? Part II: Chronic lymphocytic leukaemia. Br J Clin Pract. 1989 Oct;43(10):353-6. [PubMed:2698240 ]
  9. O'Dwyer PJ, Cheson BD, Leyland-Jones B, King SA, Hoth DF: Deoxycoformycin: an active new drug for indolent lymphomas and hairy cell leukemia. Oncology (Williston Park). 1988 Jun;2(6):17-23, 26-7. [PubMed:3079330 ]
  10. Bethlenfalvay NC, Lima JE, Banks RE: 2'-Deoxyadenosine metabolism in human and opossum Didelphis virginiana erythrocytes in vitro. Comp Biochem Physiol B. 1993 Nov;106(3):641-5. [PubMed:8281758 ]
  11. Dillman RO, Yu AL, Qiao CN: Repeated pentostatin (2'deoxycoformycin)-induced remissions in a patient with advanced chronic lymphocytic leukemia. West J Med. 1988 Mar;148(3):334-7. [PubMed:3259051 ]
  12. Catovsky D, Matutes E, Talavera JG, O'Connor NT, Johnson SA, Emmett E, Corbett L, Swansbury J: Long term results with 2'deoxycoformycin in hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:109-13. [PubMed:7820041 ]
  13. Thaler J, Dietze O, Faber V, Greil R, Gastl G, Denz H, Ho AD, Huber H: Monoclonal antibody B-ly7: a sensitive marker for detection of minimal residual disease in hairy cell leukemia. Leukemia. 1990 Mar;4(3):170-6. [PubMed:2314116 ]
  14. Ho AD, Thaler J, Willemze R, Lauria F, Derossi G, Kuse R, Stryckmans P, Blanc CM, Cataldo F, McVie G, et al.: Pentostatin (2'deoxycoformycin) for the treatment of lymphoid neoplasms. Bone Marrow Transplant. 1989 Jan;4 Suppl 1:60-2. [PubMed:2653520 ]
  15. Romo A, Lorente F, Salazar V: Action of 2'-deoxycoformycin on mitogen-induced lymphoproliferation in the neonatal period. Allergol Immunopathol (Madr). 1988 Jul-Aug;16(4):243-7. [PubMed:3265855 ]
  16. Roth E Jr, Ogasawara N, Schulman S: The deamination of adenosine and adenosine monophosphate in Plasmodium falciparum-infected human erythrocytes: in vitro use of 2'deoxycoformycin and AMP deaminase-deficient red cells. Blood. 1989 Aug 15;74(3):1121-5. [PubMed:2665862 ]
  17. Mante S, Minneman KP: Is adenosine involved in inhibition of forskolin-stimulated cyclic AMP accumulation by caffeine in rat brain? Mol Pharmacol. 1990 Nov;38(5):652-9. [PubMed:2172772 ]
  18. Fabian I, Williams Z: The effect of deoxycoformycin on bone marrow cells treated with adenosine and deoxyadenosine and hemopoietic growth factors. Hum Immunol. 1988 Feb;21(2):81-7. [PubMed:3259223 ]
  19. Montgomery RB, Kurtzberg J, Rhinehardt-Clark A, Haleen A, Ramakrishnan S, Olsen GA, Peters WP, Smith CA, Haynes BF, Houston LL, et al.: Elimination of malignant clonogenic T cells from human bone marrow using chemoimmunoseparation with 2'-deoxycoformycin, deoxyadenosine and an immunotoxin. Bone Marrow Transplant. 1990 Jun;5(6):395-402. [PubMed:2369680 ]
  20. BC Cancer Agency [Link]

Enzymes

General function:
Involved in deaminase activity
Specific function:
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion.
Gene Name:
ADA
Uniprot ID:
P00813
Molecular weight:
40764.13
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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:2433905 ]
  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:17309302 ]
  4. Cabanillas F: Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5. [PubMed:10887639 ]