Natural Product (NP) Details

General Information of the NP (ID: NP9807)
Name
Pentostatin
Synonyms
pentostatin; Deoxycoformycin; Nipent; 53910-25-1; 2'-Deoxycoformycin; 2'-DCF; CO-Vidarabine; Covidarabine; Vidarbine; CI-825; NSC-218321; YK-176; Co-V; PD-ADI; UNII-395575MZO7; 2'-Dexoycoformycin; Vira A deaminase inhibitor; PD 81565; PD-81565; 395575MZO7; (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; NCGC00182045-01; Deaminase inhibitor (PD); NSC 218321; (8R)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol; Pentostatina; Pentostatine; Pentostatinum; (R)-3-((2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,4,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol; (R)-3-(2-Deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo(4,5-d)(1,3)diazepin-8-ol; (R)-Deoxycoformycin; CL 67310465; 8R-2'-Deoxycoformycin; (R)-2'-Deoxycoformycin; Pentostatine [INN-French]; Pentostatinum [INN-Latin]; Pentostatina [INN-Spanish]; Pentostatn; Pentostatin (JAN/USAN/INN); HSDB 6547; (R)-3-(2-Deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo(4,5-d)(1,3)diazepin-8-ol; (R)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol; Pentostatin [USAN:INN:BAN:JAN]; Pentostatin (PTN); BRN 1223097; DSSTox_CID_3436; CL-67310465; Deaminase, inhibitor for adenosine arabinoside; Pentostatin(Deoxycoformycin); SCHEMBL2817; CHEMBL1580; DSSTox_RID_77027; DSSTox_GSID_23436; BIDD:GT0136; GTPL4805; DTXSID2023436; BDBM22925; Pentostatin, >=95% (HPLC); BDBM223291; AMY10324; HY-A0006; ZINC3806262; Tox21_113417; MFCD00078802; s9521; AKOS024456918; AKOS032949742; CS-0374; DB00552; PB12063; NCGC00388420-02; Imidazo[4,5-d][1,3]diazepin-8-ol, 3-(2-deoxy-.beta.-D-erythro-pentofuranosyl)-3,4,7,8-tetrahydro-, (8R)-; AB0010579; CAS-53910-25-1; A3708; C02267; D00155; Q-4464; 910P251; Q425470; SR-01000883935; J-523899; SR-01000883935-1; Adenosine Deaminase Inhibitor, DCF - CAS 53910-25-1; Z2216208604; (8R)-3-(2-Deoxy-?-D-erythro-pentofuranosyl)-3,4,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol; (8R)-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H,4H,7H,8H-imidazo[4,5-d][1,3]diazepin-8-ol; (8R)-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-8-ol; (R,Z)-3-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol; Imidazo(4,5-d)(1,3)diazepin-8-ol, 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydro-, (R)-
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Species Origin Streptomyces antiboticus ...     Click to Show/Hide
Streptomyces antiboticus
SuperKingdom: Bacteria
Phylum: Actinobacteria
Class: Actinomycetia
Order: Streptomycetales
Family: Streptomycetaceae
Genus: Streptomyces
Species: Streptomyces antiboticus
Disease Chronic lymphocytic leukaemia [ICD-11: 2A82] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.625
 
MDCK Permeability
 -5.173
 
PAMPA
 +++
 
HIA
 - - -
 
Distribution
VDss
 -0.112
 
PPB
 2.8%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - - -
HLM Stability
 - - -
 
Excretion
CLplasma
 6.644
 
T1/2
 1.782
Toxicity
DILI
 +++
 
Rat Oral Acute Toxicity
 -
 
FDAMDD
 ++
 
Respiratory
 -
 
Human Hepatotoxicity
 ++
 
Ototoxicity
 ++
 
Drug-induced Nephrotoxicity
 ++
 
Drug-induced Neurotoxicity
 +++
 
Hematotoxicity
 +
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C11H16N4O4
PubChem CID
439693
Canonical SMILES
C1C(C(OC1N2C=NC3=C2NC=NCC3O)CO)O
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
InChIKey
FPVKHBSQESCIEP-JQCXWYLXSA-N
CAS Number
CAS 53910-25-1
TTD Drug ID
D0T3AD
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Rituximab      Malignant haematopoietic neoplasm     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 The combination of a purine analog with rituximab was safe and effective for patients with recurrent HCL.
Target and Pathway
Target(s) Adenosine deaminase (ADA)  Molecule Info  [3]
BioCyc Purine nucleotides degradation Click to Show/Hide
2 Purine deoxyribonucleosides degradation
3 Purine ribonucleosides degradation to ribose-1-phosphate
4 Adenosine nucleotides degradation
5 Superpathway of purine nucleotide salvage
6 Adenine and adenosine salvage III
KEGG Pathway Purine metabolism Click to Show/Hide
2 Metabolic pathways
3 Primary immunodeficiency
NetPath Pathway TCR Signaling Pathway Click to Show/Hide
2 IL2 Signaling Pathway
Panther Pathway Adenine and hypoxanthine salvage pathway Click to Show/Hide
Pathwhiz Pathway Purine Metabolism Click to Show/Hide
Pathway Interaction Database p73 transcription factor network Click to Show/Hide
2 C-MYB transcription factor network
3 Validated transcriptional targets of deltaNp63 isoforms
4 Validated transcriptional targets of TAp63 isoforms
Reactome Purine salvage Click to Show/Hide
WikiPathways Metabolism of nucleotides Click to Show/Hide
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4805).
Reference 2 Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence. Leuk Lymphoma. 2011 Jun;52 Suppl 2:75-8.
Reference 3 Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
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