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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:43
Primary Accession Number DB00552
Secondary Accession Number
  • APRD00202
Name Pentostatin
Drug Type
  • Approved
  • Investigational
  • Small Molecule
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]
Synonyms
  1. 2'-DCF
  2. 2'-Deoxycoformycin
  3. 2'-Dexoycoformycin
  4. Deoxycoformycin
  5. pentostatin
Brand Names
  1. Co-V
  2. Co-Vidarabine
  3. Covidarabine
  4. Nipent
  5. PD-ADI
  6. Vidarbine
  7. Vira a Deaminase Inhibitor
Brand Mixtures Not Available
Chemical IUPAC Name (8R)-3-[4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7,8-dihydro-4H-imidazo[4,5-f][1,3]diazepin-8-ol
Chemical Formula C11H16N4O4
Chemical Structure Structure
CAS Registry Number 53910-25-1
InChI Identifier InChI=1/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?/m1/s1/f/h13H
InChI Key FPVKHBSQESCIEP-OCLFCWICDM
KEGG Drug D00155 Link Image
KEGG Compound C02267 Link Image
PubChem Compound 40926 Link Image
PubChem Substance 181721 Link Image
ChEBI ID Not Available
PharmGKB ID PA450863 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02011247 Link Image
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Pentostatin Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Showalter, HD et al., J. Med. Chem. 26:1478 (1983)
Average Molecular Weight 268.2691
Monoisotopic Molecular Weight 268.1172
State Solid
Melting Point 220 oC
Experimental Water Solubility 30 mg/mL Source: PhysProp
Predicted Water Solubility 1.07e+01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -1.1 Source: PhysProp
Predicted LogP -1.75 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.40 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 5.2
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES OC[C@@H]1O[C@@H](C[C@H]1O)N1C=NC2=C1NC=NC[C@H]2O
Canonical SMILES OCC1OC(CC1O)N1C=NC2=C1NC=NCC2O
Drug Category
  • Antibiotics
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Immunosuppressive Agents
ATC Codes
AHFS Codes Not Available
Indication For the treatment of hairy cell leukaemia refractory to alpha interferon.
Pharmacology 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.
Toxicity LD50=128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and myelosuppression.
Protein Binding 4%
Biotransformation Primarily hepatic, but only small amounts are metabolized.
Half Life 5.7 hours (with a range between 2.6 and 16 hrs)
Dosage Forms Not Available
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. http://www.bccancer.bc.ca/HPI/DrugDatabase/DrugIndexPro/Pentostatin.htm
  2. Drugs.com Link Image
  3. Wikipedia Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Adenosine deaminase
Drug Target 1 [top]
Target 1 ID 3957
Target 1 Name Adenosine deaminase
Target 1 Synonyms
  1. Adenosine aminohydrolase
  2. EC 3.5.4.4
Target 1 Gene Name ADA
Target 1 Protein Sequence >Adenosine deaminase 
MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPD
FLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQA
EGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAI
DLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGY
HTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIF
KSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAG
QNL
Target 1 Number of Residues 369
Target 1 Molecular Weight 40765
Target 1 Theoretical pI 5.80
Target 1 GO Classification
Function
hydrolase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines
adenosine deaminase activity
catalytic activity
deaminase activity
Process
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleotide metabolism
purine nucleotide metabolism
purine nucleotide biosynthesis
purine nucleoside monophosphate biosynthesis
purine ribonucleoside monophosphate biosynthesis
Component
Not Available
Target 1 General Function Replication, recombination and repair
Target 1 Specific Function Adenosine + H(2)O = inosine + NH(3)
Target 1 Pathways
Name SMPDB Link KEGG Link
Purine metabolism SMP00050 Link Image map00230 Link Image
Target 1 Reactions
  • adenosine + H2O = inosine + NH3
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 28380 Link Image
Target 1 UniProtKB/Swiss-Prot ID P00813 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ADA_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >1092 bp 
ATGGCCCAGACGCCCGCCTTCGACAAGCCCAAAGTAGAACTGCATGTCCACCTAGACGGA
TCCATCAAGCCTGAAACCATCTTATACTATGGCAGGAGGAGAGGGATCGCCCTCCCAGCT
AACACAGCAGAGGGGCTGCTGAACGTCATTGGCATGGACAAGCCGCTCACCCTTCCAGAC
TTCCTGGCCAAGTTTGACTACTACATGCCTGCTATCGCGGGCTGCCGGGAGGCTATCAAA
AGGATCGCCTATGAGTTTGTAGAGATGAAGGCCAAAGAGGGCGTGGTGTATGTGGAGGTG
CGGTACAGTCCGCACCTGCTGGCCAACTCCAAAGTGGAGCCAATCCCCTGGAACCAGGCT
GAAGGGGACCTCACCCCAGACGAGGTGGTGGCCCTAGTGGGCCAGGGCCTGCAGGAGGGG
GAGCGAGACTTCGGGGTCAAGGCCCGGTCCATCCTGTGCTGCATGCGCCACCAGCCCAAC
TGGTCCCCCAAGGTGGTGGAGCTGTGTAAGAAGTACCAGCAGCAGACCGTGGTGGCCATT
GACCTGGCTGGAGATGAGACCATCCCAGGAAGCAGCCTCTTGCCTGGACATGTCCAGGCC
TACCAGGAGGCTGTGAAGAGCGGCATTCACCGTACTGTCCACGCCGGGGAGGTGGGCTCG
GCCGAAGTAGTAAAAGAGGCTGTGGACATACTCAAGACAGAGCGGCTGGGACACGGCTAC
CACACCCTGGAAGACCAGGCCCTTTATAACAGGCTGCGGCAGGAAAACATGCACTTCGAG
ATCTGCCCCTGGTCCAGCTACCTCACTGGTGCCTGGAAGCCGGACACGGAGCATGCAGTC
ATTCGGCTCAAAAATGACCAGGCTAACTACTCGCTCAACACAGATGACCCGCTCATCTTC
AAGTCCACCCTGGACACTGATTACCAGATGACCAAACGGGACATGGGCTTTACTGAAGAG
GAGTTTAAAAGGCTGAACATCAATGCGGCCAAATCTAGTTTCCTCCCAGAAGATGAAAAG
AGGGAGCTTCTCGACCTGCTCTATAAAGCCTATGGGATGCCACCTTCAGCCTCTGCAGGG
CAGAACCTCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ADA Link Image
Target 1 GenAtlas ID ADA Link Image
Target 1 HGNC ID HGNC:186 Link Image
Target 1 Chromosome Location 20
Target 1 Locus 20q12-q13.11
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed Link Image]
  2. Wiginton DA, Kaplan DJ, States JC, Akeson AL, Perme CM, Bilyk IJ, Vaughn AJ, Lattier DL, Hutton JJ: Complete sequence and structure of the gene for human adenosine deaminase. Biochemistry. 1986 Dec 16;25(25):8234-44. [PubMed Link Image]
  3. Valerio D, Duyvesteyn MG, Dekker BM, Weeda G, Berkvens TM, van der Voorn L, van Ormondt H, van der Eb AJ: Adenosine deaminase: characterization and expression of a gene with a remarkable promoter. EMBO J. 1985 Feb;4(2):437-43. [PubMed Link Image]
  4. Daddona PE, Shewach DS, Kelley WN, Argos P, Markham AF, Orkin SH: Human adenosine deaminase. cDNA and complete primary amino acid sequence. J Biol Chem. 1984 Oct 10;259(19):12101-6. [PubMed Link Image]
  5. Wiginton DA, Adrian GS, Hutton JJ: Sequence of human adenosine deaminase cDNA including the coding region and a small intron. Nucleic Acids Res. 1984 Mar 12;12(5):2439-46. [PubMed Link Image]
  6. Orkin SH, Daddona PE, Shewach DS, Markham AF, Bruns GA, Goff SC, Kelley WN: Molecular cloning of human adenosine deaminase gene sequences. J Biol Chem. 1983 Nov 10;258(21):12753-6. [PubMed Link Image]
  7. Hirschhorn R, Yang DR, Israni A: An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover. Ann Hum Genet. 1994 Jan;58(Pt 1):1-9. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  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 Link Image]

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