Cladribine

Summary

Cladribine (CHEMBL1619) is an approved small-molecule antineoplastic agent (ATC L01BB04); indicated across 27 conditions including neoplasm and hairy cell leukemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01BB04 (+1 more)
• Indications: 27 conditions
• Clinical trials: 112
• Chemistry: 285.69 Da · C10H12ClN5O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1619
Name	Cladribine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	20279
ChEBI	CHEBI:567361
ATC	L01BB04, L04AA40
Molecular formula	C10H12ClN5O3
Molecular weight	285.69
InChIKey	PTOAARAWEBMLNO-KVQBGUIXSA-N

SMILES: C1[C@@H]([C@H](O[C@H]1N2C=NC3=C(N=C(N=C32)Cl)N)CO)O

IUPAC name: (2R,3S,5R)-5-(6-amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol

ChEBI definition: 2’-Deoxyadenosine in which the hydrogen at position 2 on the purine ring has been substituted by chlorine. It inhibits the synthesis and repair of DNA, particularly in lymphocytes and monocytes, and is used as an antimetabolite antineoplastic drug for the treatment of lymphoid malignancies including hairy-cell leukaemia and chronic lymphocytic leukaemia.

Pharmacological roles (ChEBI): antineoplastic agent, immunosuppressive agent.

Also known as: Cladaribine, Cladribina, Cladribine, Leustat, Leustatin, Litak, Mavenclad, NSC-05014, NSC-105014, RWJ 26251, RWJ-26251, cladribine

Patent coverage: 22,210 distinct patent families (91,402 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 90,947 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Nuclear receptor ROR-gamma, Survival motor neuron protein, Prelamin-A/C, Relaxin receptor 1, cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A, 3’,5’-cyclic-AMP phosphodiesterase 4D, Adenosine receptor A2a, Adenosine receptor A1, Cellular tumor antigen p53, Purine nucleoside phosphorylase.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PNP	8.64	Ki	2.3	nM	CHEMBL_ACT_25994948
LMNA	7.3	Potency	50.1	nM	CHEMBL_ACT_3665389
LMNA	6.15	Potency	707.9	nM	CHEMBL_ACT_3662199
LMNA	6.1	Potency	794.3	nM	CHEMBL_ACT_3654667
PDE4D	6.01	AC50	970	nM	CHEMBL_ACT_25185934
HTT	5.35	Potency	4467	nM	CHEMBL_ACT_3758468
SMN1	5.2	Potency	6310	nM	CHEMBL_ACT_3894237
P25099	5.13	Ki	7320	nM	CHEMBL_ACT_1157764
SMN1	5.05	Potency	8912	nM	CHEMBL_ACT_3878987

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

27 indications (5 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
neoplasm	4	MONDO:0005070	EFO:0000616
hairy cell leukemia	4	MONDO:0018935	EFO:1000956
immune system disorder	4	MONDO:0005046	EFO:0000540
anemia	4	MONDO:0002280	MONDO:0002280
multiple sclerosis	4	MONDO:0005301	MONDO:0005301
relapsing-remitting multiple sclerosis	3	MONDO:0005314	EFO:0003929
leukemia	3	MONDO:0005059	EFO:0000565
lymphoma	3	MONDO:0005062	EFO:0000574
B-cell chronic lymphocytic leukemia	3	MONDO:0004948	EFO:0000095
acute myeloid leukemia	3	MONDO:0018874	EFO:0000222
peripheral T-cell lymphoma, not otherwise specified	3	MONDO:0004964	EFO:0000211
histiocytosis	2	MONDO:0002637	HP:0100727
myelodysplastic syndrome	2	MONDO:0018881	EFO:0000198
acute lymphoblastic leukemia	2	MONDO:0004967	EFO:0000220
sclerosing cholangitis	2	MONDO:0018646	EFO:0004268
Langerhans cell histiocytosis	2	MONDO:0018310	EFO:1000318
mantle cell lymphoma	2	MONDO:0018876	EFO:1001469
MALT lymphoma	2	MONDO:0007650	EFO:0000191
myeloid leukemia	2	MONDO:0004643	MONDO:0004643
acute biphenotypic leukemia	2	MONDO:0020322	MONDO:0019460
chronic progressive multiple sclerosis	2	MONDO:0005284	EFO:0003840
plasma cell myeloma	1	MONDO:0009693	EFO:0001378
myeloproliferative neoplasm	1	MONDO:0020076	EFO:0002428
central nervous system neoplasm	1	MONDO:0006130	EFO:1000158
graft versus host disease	1	MONDO:0013730	MONDO:0013730
plasma cell neoplasm	1	MONDO:0004959	EFO:0000200

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 112.

Phase distribution

Phase	Trials
PHASE2	45
PHASE1	17
PHASE1/PHASE2	13
PHASE3	12
Not specified	11
PHASE2/PHASE3	8
PHASE4	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04178005	PHASE4	ACTIVE_NOT_RECRUITING	Cladribine Tablets After Treatment With Natalizumab (CLADRINA)
NCT06763666	PHASE4	NOT_YET_RECRUITING	CLAG+VEN vs CLAG in the Treatment of Relapsed/Refractory AML
NCT00198991	PHASE4	COMPLETED	German Multicenter Trial for Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Adults (07/2003)
NCT00199017	PHASE4	COMPLETED	German Multicenter Trial for the Treatment of Newly Diagnosed T-lymphoblastic Lymphoma in Adults
NCT03963375	PHASE4	COMPLETED	Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis
NCT04550455	PHASE4	UNKNOWN	A Prospective Biomarker Study in Active SPMS Subjects Treated With Cladribine Tablets
NCT02205762	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis
NCT03477500	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Autologous heMatopoietic Stem Cell Transplantation Versus Alemtuzumab, Cladribine or Ocrelizumab for RRMS (RAM-MS)
NCT04695080	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	ChariotMS - Cladribine to Halt Deterioration in People With Advanced Multiple Sclerosis
NCT04708054	PHASE2/PHASE3	RECRUITING	Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS
NCT05961644	PHASE2/PHASE3	RECRUITING	Cladribine vs Placebo for Non-active Progressive Multiple Sclerosis (CLASP-MS).
NCT00003746	PHASE3	COMPLETED	Daily or Weekly Cladribine in Treating Patients With Hairy Cell Leukemia
NCT00111345	PHASE2/PHASE3	UNKNOWN	Therapy-Optimization Trial for the Treatment of Acute Myeloid Leukemias (AML) in Children and Adolescents
NCT00136084	PHASE3	COMPLETED	Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00213135	PHASE3	COMPLETED	A Safety and Efficacy Study of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
NCT00641537	PHASE3	COMPLETED	CLARITY Extension Study
NCT00718549	PHASE3	COMPLETED	A Study to Assess the Effect of Maintenance Treatment With Rituximab Versus No Treatment in Participants With Progressive B-Cell Chronic Lymphocytic Leukemia (CLL)
NCT00725985	PHASE3	COMPLETED	Oral Cladribine in Early Multiple Sclerosis (MS)
NCT01602939	PHASE2/PHASE3	UNKNOWN	Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis
NCT03384212	PHASE3	UNKNOWN	CBA Versus FBA Conditioning Followed by Allogeneic HSCT in Treatment of High Risk and Refractory AML
NCT03384225	PHASE3	UNKNOWN	CBA Versus FBA Conditioning Followed by Haploidentical Allogeneic HSCT in Treatment of High Risk and Refractory AML
NCT03926624	PHASE3	TERMINATED	Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd/4th Salvage
NCT04121403	PHASE3	COMPLETED	Norwegian Study of Oral Cladribine and Rituximab in Multiple Sclerosis (NOR-MS)
NCT05313958	PHASE2/PHASE3	UNKNOWN	Treateament of Newly Diagnosed Acute Monocytic Leukemia in Children
NCT05466318	PHASE3	UNKNOWN	ChiCGB vs BEAM in High-risk or R/R Lymphomas
NCT05578378	PHASE2/PHASE3	UNKNOWN	Cladribine Combined With G-CSF and Cytarabine as a Salvage Treatment in R/R ALL
NCT00412594	PHASE2	RECRUITING	Cladribine and Rituximab in Treating Patients With Hairy Cell Leukemia
NCT00923013	PHASE2	ACTIVE_NOT_RECRUITING	Cladribine With Simultaneous or Delayed Rituximab to Treat Hairy Cell Leukemia
NCT01515527	PHASE2	RECRUITING	Cladribine Plus Low Dose Cytarabine (LDAC) Alternating With Decitabine in Patients With Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)
NCT02115295	PHASE2	RECRUITING	Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia
NCT02250937	PHASE2	ACTIVE_NOT_RECRUITING	Venetoclax and Sequential Busulfan, Cladribine, and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
NCT03586609	PHASE2	RECRUITING	Venetoclax, Cladribine, Low Dose Cytarabine, and Azacitidine in Treating Patients With Previously Untreated Acute Myeloid Leukemia
NCT03589729	PHASE2	RECRUITING	Dexrazoxane Hydrochloride in Preventing Heart-Related Side Effects of Chemotherapy in Participants With Blood Cancers
NCT04047641	PHASE1/PHASE2	RECRUITING	Cladribine, Idarubicin, Cytarabine, and Quizartinib in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
NCT04195945	PHASE2	ACTIVE_NOT_RECRUITING	CPX-351 or CLAG-M Regimen for the Treatment of Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms in Medically Less-Fit Patients
NCT04797767	PHASE1/PHASE2	RECRUITING	Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
NCT04861207	PHASE2	ACTIVE_NOT_RECRUITING	Total Body Irradiation and Cladribine Before Allogeneic Hematopoietic Cell Transplantation in Patients With AML (Acute Myeloid Leukemia) and Myelodysplastic Syndromes
NCT05365035	PHASE2	RECRUITING	A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts
NCT06232655	PHASE2	RECRUITING	Cladribine Venetoclax in Monocytic AML
NCT06504459	PHASE2	RECRUITING	Venetoclax in Combination With Cladribine and Cytarabine Alternating With Azacitidine Plus Venetoclax for the Treatment of Newly Diagnosed Monocytic AML and Active Signaling Mutated AML

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 9 clinical and 9 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).