Clofarabine

Summary

Clofarabine (CHEMBL1750) is an approved small-molecule antineoplastic agent (ATC L01BB06) targeting RRM1 and RRM2; indicated across 22 conditions including acute lymphoblastic leukemia and neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01BB06
• Targets: 2 (RRM1, RRM2)
• Indications: 22 conditions
• Clinical trials: 152
• Chemistry: 303.68 Da · C10H11ClFN5O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1750
Name	Clofarabine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	119182
ChEBI	CHEBI:681569
ATC	L01BB06
Molecular formula	C10H11ClFN5O3
Molecular weight	303.68
InChIKey	WDDPHFBMKLOVOX-AYQXTPAHSA-N

SMILES: C1=NC2=C(N=C(N=C2N1[C@H]3[C@H]([C@@H]([C@H](O3)CO)O)F)Cl)N

IUPAC name: (2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol

ChEBI definition: A purine nucleoside analogue consisting of a 6-amino-2-chloropurin-9-yl group attached to the 1β position of 2’-deoxy-2’-fluoro-D-arabinofuranose. It is metabolized intracellularly to the active 5’-triphosphate metabolite, which inhibits DNA synthesisis and so stops the growth of cancer cells. Clofarabine is used as an antimetabolite antineoplastic agent in the treatment of relapsed or refractory acute lymphoblastic leukaemia.

Pharmacological roles (ChEBI): antineoplastic agent.

Other ChEBI roles (chemical / environmental): antimetabolite.

Also known as: Clofarabina, Clofarabine, Clolar, Evoltra, Ivozall, NSC-759857, clofarabine, CLOFARABINE, cfb, SID144205735, SID170465145, ClofarabineÊ

Patent coverage: 7,928 distinct patent families (31,786 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 31,404 (99%) 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

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
RRM1	ribonucleotide reductase catalytic subunit M1	Inhibition	8.3	100% (common-essential)	P23921
RRM2	ribonucleotide reductase regulatory subunit M2	Inhibition	8.3	99.8% (common-essential)	P31350

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: Adenosine receptor A1, Alpha-1A adrenergic receptor, cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A, Adenosine receptor A2a, Adenosine receptor A3, cGMP-dependent 3’,5’-cyclic phosphodiesterase, 3’,5’-cyclic-AMP phosphodiesterase 4D.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PDE4D	6.77	AC50	170	nM	CHEMBL_ACT_25185935
ADORA1	5.64	AC50	2300	nM	CHEMBL_ACT_25133578
PDE2A	5.51	IC50	3120	nM	CHEMBL_ACT_18469212
PDE2A	5.51	IC50	3120	nM	CHEMBL_ACT_26105933
PDE3A	5.19	AC50	6400	nM	CHEMBL_ACT_25191300

Target pathways

Aggregated over 2 target gene(s): RRM1, RRM2.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Interconversion of nucleotide di- and triphosphates	2	RRM1, RRM2
G1/S-Specific Transcription	1	RRM2
Transcriptional Regulation by E2F6	1	RRM2

Dominant GO biological processes

GO term	Targets
DNA repair	2
ribonucleoside diphosphate metabolic process	2
deoxyribonucleotide biosynthetic process	2
2’-deoxyribonucleotide biosynthetic process	2
protein heterotetramerization	2
positive regulation of G1/S transition of mitotic cell cycle	2
DNA synthesis involved in DNA repair	1
pyrimidine nucleobase metabolic process	1
mitochondrial DNA replication	1
male gonad development	1
response to ionizing radiation	1
positive regulation of G2/M transition of mitotic cell cycle	1
cell proliferation in forebrain	1
retina development in camera-type eye	1
positive regulation of G0 to G1 transition	1

Indications & clinical

Indications

22 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
acute lymphoblastic leukemia	4	MONDO:0004967	EFO:0000220
neoplasm	4	MONDO:0005070	EFO:0000616
lymphoid leukemia	4	MONDO:0005402	EFO:0004289
leukemia	3	MONDO:0005059	EFO:0000565
acute myeloid leukemia	3	MONDO:0018874	EFO:0000222
myelodysplastic syndrome	2	MONDO:0018881	EFO:0000198
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
B-cell chronic lymphocytic leukemia	2	MONDO:0004948	EFO:0000095
non-Hodgkin lymphoma	2	MONDO:0018908	EFO:0005952
chronic myelomonocytic leukemia	2	MONDO:0020311	EFO:1001779
Hodgkins lymphoma	2	MONDO:0004952	EFO:0000183
chronic myeloid leukemia	2	MONDO:0011996	EFO:0000339
lymphoma	2	MONDO:0005062	EFO:0000574
Langerhans cell histiocytosis	2	MONDO:0018310	EFO:1000318
hematologic disorder	2	MONDO:0005570	EFO:0005803
graft versus host disease	2	MONDO:0013730	MONDO:0013730
osteopetrosis	2	MONDO:0017198	MONDO:0017198
acute biphenotypic leukemia	2	MONDO:0020322	MONDO:0019460
neoplasm of mature B-cells	1	MONDO:0004949	EFO:0000096
acute promyelocytic leukemia	1	MONDO:0012883	EFO:0000224

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

Clinical trials

Total trials: 152.

Phase distribution

Phase	Trials
PHASE2	76
PHASE1	36
PHASE1/PHASE2	29
PHASE3	5
PHASE2/PHASE3	3
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03117751	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma
NCT00454480	PHASE2/PHASE3	COMPLETED	Combination Chemotherapy With or Without Gemtuzumab Ozogamicin or Tipifarnib in Treating Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes
NCT00549848	PHASE3	COMPLETED	Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
NCT00703820	PHASE3	COMPLETED	Clofarabine Plus Cytarabine Versus Conventional Induction Therapy And A Study Of NK Cell Transplantation In Newly Diagnosed Acute Myeloid Leukemia
NCT01228331	PHASE2/PHASE3	COMPLETED	Clofarabine or High-Dose Cytarabine and Pegaspargase in Children with ALL
NCT01471444	PHASE3	COMPLETED	Fludarabine-IV Busulfan ± Clofarabine and Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
NCT02085408	PHASE3	COMPLETED	Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT02883049	PHASE3	COMPLETED	Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations
NCT01885689	PHASE2	ACTIVE_NOT_RECRUITING	Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
NCT02425904	PHASE2	ACTIVE_NOT_RECRUITING	Study of Clofarabine in Patients With Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-related Disorders
NCT02727803	PHASE2	RECRUITING	Personalized NK Cell Therapy in CBT
NCT03136146	PHASE2	RECRUITING	Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma, Burkitt Lymphoma/Leukemia, or Double-Hit Lymphoma/Leukemia
NCT04644016	PHASE2	RECRUITING	Cord Blood Transplant in Children and Young Adults With Blood Cancers and Non-malignant Disorders
NCT04994808	PHASE2	ACTIVE_NOT_RECRUITING	Treosulfan-Based Versus Clofarabine-Based Conditioning Before Donor Hematopoietic Stem Cell Transplant for the Treatment of Myelodysplastic Syndromes or Acute Myeloid Leukemia
NCT05917405	PHASE2	RECRUITING	Study Comparing the Efficacy of 2 RIC Regimens (Clofarabine vs Fludarabine) in Adults With AML Eligible to Allo-SCT
NCT06252870	PHASE2	RECRUITING	Study Testing Two Conditioning Regimen With a Single Prophylaxis of GVHD by Cyclophosphamide and Methotrexate Post-transplant in Patients Eligible for Matched-donor Allograft Transplantation
NCT06986382	PHASE1/PHASE2	NOT_YET_RECRUITING	Phase 1b/2a Trial of Allogeneic HSCT From an HLA-partially Matched Related or Unrelated Donor After TCRab+ T-cell/CD19+ B-cell Depletion for Patients With Monogenic and/or Early-onset Medically Refractory Crohn Disease
NCT07022834	PHASE2	RECRUITING	Real-world Study of Darafenib or Trametinib and Clofarabine for High-risk/Recurrent/Refractory Langerhans Cell Histiocytosis in Children
NCT07034053	PHASE1/PHASE2	RECRUITING	Clofarabine Therapy in Locally Advanced or Metastatic Urothelial Carcinoma
NCT07566377	PHASE2	RECRUITING	Cord Blood Transplantation in Children and Young Adults With Blood Cancer
NCT00065143	PHASE2	COMPLETED	Clofarabine Plus Cytarabine in Patients With Previously Untreated Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome
NCT00067028	PHASE2	COMPLETED	Clofarabine Combinations in Relapsed/Refractory Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS) and Myeloid Blast Phase Chronic Myeloid Leukemia (CML)
NCT00088218	PHASE2	COMPLETED	Clofarabine vs Clofarabine in Plus With Low-Dose Ara-C in Previously Untreated Patients With Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS).
NCT00098033	PHASE2	COMPLETED	Investigation of Clofarabine in Acute Leukemias
NCT00156013	PHASE1/PHASE2	COMPLETED	Clofarabine for Relapsed or Refractory T-Cell or B-Cell Non-Hodgkin Lymphoma (NHL)
NCT00201669	PHASE2	COMPLETED	A Phase II Study of Clofarabine in Patients With Aggressive Non-Hodgkin’s Lymphoma
NCT00241371	PHASE2	TERMINATED	A Phase II Study of Clofarabine in Patients With Relapsed or Refractory Multiple Myeloma
NCT00299156	PHASE2	COMPLETED	Oral Clofarabine Study in Patients With Myelodysplastic Syndrome
NCT00315705	PHASE1/PHASE2	COMPLETED	A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias.
NCT00334074	PHASE2	COMPLETED	Clofarabine and Ara-C for the Treatment of Relapsed AML and Untreated MDS
NCT00337168	PHASE2	COMPLETED	S0530 Cytarabine and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
NCT00372619	PHASE1/PHASE2	COMPLETED	Clofarabine and Cytarabine in Treating Young Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia
NCT00373529	PHASE2	COMPLETED	A Study of Clofarabine for Older Patients With Newly Diagnosed Acute Myelogenous Leukemia (AML) (CLASSIC II)
NCT00383448	PHASE2	COMPLETED	HSCT for High Risk Inherited Inborn Errors
NCT00412243	PHASE1/PHASE2	COMPLETED	Clofarabine and Cyclophosphamide Combination in Acute Lymphoblastic Leukemia Patients
NCT00416351	PHASE1/PHASE2	COMPLETED	Clofarabine in Treating Patients With T-Cell or Natural Killer-Cell Non-Hodgkin’s Lymphoma That Has Relapsed or Not Responded to Previous Treatment
NCT00422032	PHASE2	COMPLETED	2 Arm Study of Clofarabine IV in MDS Patients
NCT00423514	PHASE1/PHASE2	COMPLETED	Clofarabine, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk and/or Advanced Hematologic Cancer or Other Disease
NCT00469014	PHASE2	COMPLETED	Busulfan, Fludarabine, Clofarabine With Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia
NCT00503880	PHASE1/PHASE2	TERMINATED	Clofarabine, Cytarabine, and G-CSF in Treating Patients With Myelodysplastic Syndromes

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

4 molecules share ≥1 primary target. Top 4 by shared-target count:

Molecule	Source	Status	Shared targets
TRIAPINE	ChEMBL	Phase 3	RRM1, RRM2
Fludarabine	PubChem	Approved	RRM1, RRM2
Gemcitabine	PubChem	Approved	RRM1, RRM2
Hydroxyurea	PubChem	Approved	RRM1, RRM2