Drug Information

Drug (ID: DG00883) and It's Reported Resistant Information

• 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; MLS000028377; 2CdA; Cladarabine; RWJ-26251; (2R,3S,5R)-5-(6-amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol; Leustat; SMR000058553; (2R,3S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol; (2R,3S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol; 2-chloro-6-amino-9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine; CHEBI:567361; 47M74X9YT5; MFCD00153939; NSC-105014; Movectro; Mylinax; DSSTox_CID_2828; 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; Cladribine- Bio-X; 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; 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; BC164318; BP-25407; HY-13599; SW197746-4; D01370; AB00382963-17; AB00382963_19; 291C638; A826062; Q414030; 2-Chloro-2 inverted exclamation marka-deoxyadenosine; 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-chloropurin-9-yl)-2-(hydroxymethyl)oxalan-3-ol; (2R,3S,5R)-5-(6-amino-2-chloro-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol; Cladribine for peak identification, European Pharmacopoeia (EP) Reference Standard; 2-Chloro-2'-deoxyadenosine;(2R,3S,5R)-5-(6-amino-2-chloro-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol; 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
• Indication:
  In total 3 Indication(s)
  Hairy cell leukaemia [ICD-11: 2A82]; Approved; [1]
  Multiple sclerosis [ICD-11: 8A40]; Approved; [1]
  Relapsing-remitting multiple sclerosis [ICD-11: 8A40]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Acute lymphocytic leukemia [ICD-11: 2B33]; [1]
• Target: Adenosine deaminase (ADA); ADA_HUMAN; [1]
• Formula: C10H12ClN5O3
• IsoSMILES: C1[C@@H]([C@H](O[C@H]1N2C=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
• PubChem CID: 20279
• ChEBI ID: CHEBI:567361
• TTD Drug ID: D05GJW
• VARIDT ID: DR00087
• INTEDE ID: DR1918
• DrugBank ID: DB00242

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Deoxycytidine kinase (DCK) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain; 1280
• Mechanism Description: Cladribine cannot be deaminated by adenosine deaminase(ADA) and is phosphorylated to cladribine-MP by dCK. Cladribine self potentiates its own activation by activation of dCK. The cytotoxicity mainly depends on the accumulation of cladribine-TP after phosphoryl-ation of cladribine-MP by nucleoside MP kinase and nucleoside diphosphate kinase in the cells. Down regulation of all activating enzymes such as dCK or dGK due to loss of expression or through mutation, has been shown to cause resistance to cladribine. However, the most frequently described form of acquired resistance to cladribine in vitro is dCK de ciency and reduction in dCK activity is probably the major determinant of cladribine resistance.

Key Molecule: Diacylglycerol kinase iota (DGKI) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain; 1280
• Mechanism Description: Cladribine cannot be deaminated by adenosine deaminase(ADA) and is phosphorylated to cladribine-MP by dCK. Cladribine self potentiates its own activation by activation of dCK. The cytotoxicity mainly depends on the accumulation of cladribine-TP after phosphoryl-ation of cladribine-MP by nucleoside MP kinase and nucleoside diphosphate kinase in the cells. Down regulation of all activating enzymes such as dCK or dGK due to loss of expression or through mutation, has been shown to cause resistance to cladribine. However, the most frequently described form of acquired resistance to cladribine in vitro is dCK de ciency and reduction in dCK activity is probably the major determinant of cladribine resistance.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Solute carrier family 29 member 1 (SLC29A1) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain; 1280
• Mechanism Description: Resistance of cytarabine resistant CEM cells to cladribine, among other purine and pyrimidine nucleoside drugs, was due to the absence of expression of the hENT1 gene leading to a loss ofnucleoside transport activity. Stable transfer of hCNT2 DNA into these resistant cells partially restored chemosensitivity for cladribine.

References

• Ref 1: Pharmacological basis for cladribine resistance .Leuk Lymphoma. 2003 Oct;44(10):1705-12. doi: 10.1080/1042819031000099698. 10.1080/1042819031000099698