Natural Product (NP) Details

General Information of the NP (ID: NP5000)
Name
Cladribine
Synonyms
Cladribine; 2-Chloro-2'-deoxyadenosine; 4291-63-8; Leustatin; 2-Chlorodeoxyadenosine; 2-CdA; Chlorodeoxyadenosine; CldAdo; ADENOSINE, 2-CHLORO-2'-DEOXY-; Litak; 2-Chloro-2'-deoxy-beta-adenosine; Cladaribine; RWJ 26251; 2-chloro-deoxyadenosine; 2ClAdo; UNII-47M74X9YT5; (2R,3S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol; MLS000028377; (2R,3S,5R)-5-(6-amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol; Cladarabine; RWJ-26251; Leustat; SMR000058553; 2-chloro-6-amino-9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine; CHEBI:567361; 47M74X9YT5; MFCD00153939; NSC-105014; 2CdA; Movectro; Mylinax; DSSTox_CID_2828; (2R,3S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol; DSSTox_RID_76747; DSSTox_GSID_22828; cladribina; cladribinum; mavenclad; Leustatin (TN); CL9; CAS-4291-63-8; 2 Chlorodeoxyadenosine; SR-01000003063; NSC 105014; BRN 0624220; Cladiribine; CCRIS 9374; Adenosine, 2-chloro-2'-deoxy; HSDB 7564; 2-Chloro-6-amino-9-(2-deoxy-beta-D-erythropentofuranosyl)purine; Cladribine [USAN:USP:INN:BAN]; Mavenclad (TN); NCGC00018167-03; S1199; RWJ-26251-000; Opera_ID_1191; SCHEMBL3775; CHEMBL1619; Cladribine (JAN/USP/INN); 2-chloro-2'-deoxy-adenosine; cid_20279; MLS000028484; MLS000759397; MLS001077345; MLS001424194; GTPL4799; DTXSID8022828; BDBM38920; HMS2052K13; HMS2232C23; HMS3715F17; ACT02615; AMY22140; BCP02868; ZINC3798064; Tox21_110834; Tox21_300596; CC0168; NSC-05014; NSC-105014-F; AKOS015854898; AKOS015892544; AC-7591; BCP9000538; CCG-101116; CS-2057; DB00242; NC00366; NCGC00022567-05; NCGC00022567-06; NCGC00022567-07; NCGC00022567-08; NCGC00164384-01; NCGC00254518-01; 2-Chloro-2'-deoxyadenosine, antileukemic; AS-12366; BP-25407; HY-13599; AB0011806; SW197746-4; D01370; S-7479; AB00382963-17; AB00382963_19; 291C638; A826062; Q414030; SR-01000003063-7; SR-01000003063-10; Cladribine, European Pharmacopoeia (EP) Reference Standard; 6-amino-2-chloro-9-(2-deoxy-beta-erythropentofuranosyl)purine; Cladribine, United States Pharmacopeia (USP) Reference Standard; 6-amino-2-chloro-9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine; (2R,3S,5R)-5-(6-amino-2-chloro-9-purinyl)-2-(hydroxymethyl)-3-oxolanol; (2R,3S,5R)-5-(6-Amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxalan-3-ol; (2R,3S,5R)-5-(6-amino-2-chloro-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol; (2R,3S,5R)-5-(6-azanyl-2-chloranyl-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol; Cladribine for peak identification, European Pharmacopoeia (EP) Reference Standard; 24757-90-2; Leustatin; ; ; 2-Chloro-2'-deoxyadenosine; ; ; 2-CdA; ; ; NSC-105014-F; ; ; (2R,3S,5R)-5-(6-Amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
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Species Origin Homo sapiens ...     Click to Show/Hide
Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Disease Chronic lymphocytic leukaemia [ICD-11: 2A82] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.807
 
MDCK Permeability
 -5.099
 
PAMPA
 +++
 
HIA
 - - -
 
Distribution
VDss
 0.964
 
PPB
 19.3%
 
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
 12.562
 
T1/2
 1.721
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
C10H12ClN5O3
PubChem CID
20279
Canonical SMILES
C1C(C(OC1N2C=NC3=C(N=C(N=C32)Cl)N)CO)O
InChI
1S/C10H12ClN5O3/c11-10-14-8(12)7-9(15-10)16(3-13-7)6-1-4(18)5(2-17)19-6/h3-6,17-18H,1-2H2,(H2,12,14,15)/t4-,5+,6+/m0/s1
InChIKey
PTOAARAWEBMLNO-KVQBGUIXSA-N
CAS Number
CAS 4291-63-8
ChEBI ID
CHEBI:567361
TTD Drug ID
D05GJW
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Entinostat      Breast cancer     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
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
                    In-vitro Model RPMI-8226 CVCL_0014 Plasma cell myeloma Homo sapiens
U266B1 CVCL_0566 Plasma cell myeloma Homo sapiens
MM1.R CVCL_8794 Plasma cell myeloma Homo sapiens
                    Experimental
                    Result(s)		 Combinations of cladribine and entinostat exhibit potent activity to induce anti-proliferative/anti-survival effects on MM cells via induction of cell cycle G1 arrest, apoptosis, and DNA damage response.
          S3I-201      Lupus nephritis     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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model U266B1 CVCL_0566 Plasma cell myeloma Homo sapiens
RPMI-8226 CVCL_0014 Plasma cell myeloma Homo sapiens
MM1.S CVCL_8792 Plasma cell myeloma Homo sapiens
                    Experimental
                    Result(s)		 Cladribine exhibited inhibitory effects on MM cells in vitro. MM1.S is the only cell line showing significant response to the clinically achievable concentrations of cladribine-induced apoptosis and inactivation of STAT3.
          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 [4]
                    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.
          Gemcitabine + Busulfan + Vorinostat     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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model J45.01 CVCL_2530 T acute lymphoblastic leukemia Homo sapiens
U-937 CVCL_0007 Adult acute monocytic leukemia Homo sapiens
                    Experimental
                    Result(s)		 The Clad+Gem+Bu+SAHA combination provides synergistic cytotoxicity in lymphoma cell lines.
Target and Pathway
Target(s) Adenosine deaminase (ADA)  Molecule Info  [6]
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: 4799).
Reference 2 Cladribine in combination with entinostat synergistically elicits anti-proliferative/anti-survival effects on multiple myeloma cells. Cell Cycle. 2018;17(8):985-996.
Reference 3 Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma. BMC Cancer. 2011 Jun 16;11:255.
Reference 4 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 5 Cladribine, gemcitabine, busulfan, and SAHA combination as a potential pretransplant conditioning regimen for lymphomas: A preclinical study. Exp Hematol. 2016 Jun;44(6):458-65.
Reference 6 Cladribine: from the bench to the bedside--focus on hairy cell leukemia. Expert Rev Anticancer Ther. 2004 Oct;4(5):745-57.
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