Pentostatin
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Also known as CI-825DeoxycoformycinNipentNSC-218321PD 81565PD-81565PentostatinaPentostatineYK-176dcfSID144206967
Summary
Pentostatin (CHEMBL1580) is an approved small-molecule EC 3.5.4.4 (adenosine deaminase) inhibitor (ATC L01XX08) targeting ADA; indicated across 13 conditions including neoplasm and hairy cell leukemia.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: L01XX08
- Targets: 1 (ADA)
- Indications: 13 conditions
- Clinical trials: 47
- Chemistry: 268.27 Da · C11H16N4O4
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1580 |
| Name | Pentostatin |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 439693 |
| ChEBI | CHEBI:27834 |
| ATC | L01XX08 |
| Molecular formula | C11H16N4O4 |
| Molecular weight | 268.27 |
| InChIKey | FPVKHBSQESCIEP-JQCXWYLXSA-N |
SMILES: C1[C@@H]([C@H](O[C@H]1N2C=NC3=C2NC=NC[C@H]3O)CO)O
IUPAC name: (8R)-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-8-ol
ChEBI definition: A member of the class of coformycins that is coformycin in which the hydroxy group at position 2’ is replaced with a hydrogen. It is a drug used for the treatment of hairy cell leukaemia.
Pharmacological roles (ChEBI): EC 3.5.4.4 (adenosine deaminase) inhibitor, antineoplastic agent.
Other ChEBI roles (chemical / environmental): antimetabolite, bacterial metabolite, Aspergillus metabolite.
Also known as: CI-825, Deoxycoformycin, Nipent, NSC-218321, PD 81565, PD-81565, Pentostatin, Pentostatina, Pentostatine, YK-176, PENTOSTATIN, dcf
Patent coverage: 25,090 distinct patent families (103,826 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 102,989 (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 |
|---|---|---|---|---|---|
| ADA | Adenosine deaminase | Inhibition | 10.8 | 0.2% | P00813 |
Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Adenosine deaminase, Adenosine receptor A1, Adenosine receptor A2a, Adenosine receptor A3, Adenosine deaminase, Prostaglandin G/H synthase 1.
Bioactivity
ChEMBL activities: 9 potent at pChembl ≥ 5 of 9 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| P56658 | 11 | Ki | 0.01 | nM | CHEMBL_ACT_1148728 |
| ADA | 10.59 | Ki | 0.03 | nM | CHEMBL_ACT_19143402 |
| ADA | 10.48 | Ki | 0.03 | nM | CHEMBL_ACT_372606 |
| ADA | 10 | Ki | 0.1 | nM | CHEMBL_ACT_205842 |
| ADA | 9.3 | Ki | 0.5 | nM | CHEMBL_ACT_19143399 |
| ADORA1 | 6.39 | AC50 | 410 | nM | CHEMBL_ACT_25132754 |
| ADORA2A | 5.47 | AC50 | 3400 | nM | CHEMBL_ACT_25152222 |
| ADORA3 | 5.44 | AC50 | 3600 | nM | CHEMBL_ACT_25133950 |
| Q63921 | 5.18 | AC50 | 6600 | nM | CHEMBL_ACT_25174141 |
Target pathways
Aggregated over 1 target gene(s): ADA.
Top Reactome pathways
11 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Metabolism | 1 | ADA |
| Metabolism of nucleotides | 1 | ADA |
| Disease | 1 | ADA |
| Diseases of metabolism | 1 | ADA |
| Purine salvage | 1 | ADA |
| Nucleotide salvage | 1 | ADA |
| Nucleotide salvage defects | 1 | ADA |
| Defective ADA disrupts (deoxy)adenosine deamination | 1 | ADA |
| Diseases of nucleotide metabolism | 1 | ADA |
| Drug ADME | 1 | ADA |
| Ribavirin ADME | 1 | ADA |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| allantoin metabolic process | 1 |
| response to hypoxia | 1 |
| trophectodermal cell differentiation | 1 |
| liver development | 1 |
| placenta development | 1 |
| germinal center B cell differentiation | 1 |
| germinal center formation | 1 |
| positive regulation of germinal center formation | 1 |
| negative regulation of leukocyte migration | 1 |
| mature B cell apoptotic process | 1 |
| negative regulation of mature B cell apoptotic process | 1 |
| adenosine catabolic process | 1 |
| deoxyadenosine catabolic process | 1 |
| AMP catabolic process | 1 |
| xenobiotic metabolic process | 1 |
Indications & clinical
Indications
13 indications (4 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 |
| anemia | 4 | MONDO:0002280 | MONDO:0002280 |
| B-cell chronic lymphocytic leukemia | 3 | MONDO:0004948 | EFO:0000095 |
| graft versus host disease | 3 | MONDO:0013730 | MONDO:0013730 |
| leukemia | 2 | MONDO:0005059 | EFO:0000565 |
| lymphoma | 2 | MONDO:0005062 | EFO:0000574 |
| kidney cancer | 1 | MONDO:0002367 | MONDO:0002367 |
| sickle cell disease | 1 | MONDO:0011382 | MONDO:0011382 |
| aplastic anemia | 1 | MONDO:0015909 | EFO:0006927 |
| B-cell non-Hodgkin lymphoma | 1 | MONDO:0015759 | EFO:1001938 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 47.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 30 |
| PHASE1/PHASE2 | 8 |
| PHASE1 | 4 |
| PHASE3 | 3 |
| PHASE4 | 1 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00131313 | PHASE4 | UNKNOWN | Efficacy and Safety of Nipent, Cytoxan and Rituxan in the Treatment of Chronic Lymphocytic Leukemia. |
| NCT00254163 | PHASE3 | COMPLETED | Fludarabine, Cyclophosphamide, and Rituximab Versus Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-Cell Chronic Lymphocytic Leukemia Patients |
| NCT01188798 | PHASE3 | COMPLETED | Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies |
| NCT03112603 | PHASE3 | COMPLETED | A Study of Ruxolitinib vs Best Available Therapy (BAT) in Patients With Steroid-refractory Chronic Graft vs. Host Disease (GvHD) After Bone Marrow Transplantation (REACH3) |
| NCT01059786 | PHASE2 | ACTIVE_NOT_RECRUITING | Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia |
| NCT02105766 | PHASE2 | ACTIVE_NOT_RECRUITING | Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure |
| NCT03077542 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease |
| NCT03663933 | PHASE2 | ACTIVE_NOT_RECRUITING | Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation |
| NCT00003658 | PHASE2 | COMPLETED | Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Other B-cell Cancers |
| NCT00006968 | PHASE1/PHASE2 | COMPLETED | Pentostatin Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Kidney Cancer |
| NCT00026351 | PHASE2 | COMPLETED | Pentostatin and Rituximab in Treating Patients With Low-Grade Non-Hodgkin’s Lymphoma or Chronic Lymphocytic Leukemia |
| NCT00032773 | PHASE1/PHASE2 | TERMINATED | Dose-finding Study Using Pentostatin for Injection in the Treatment of Steroid-refractory aGvHD |
| NCT00038025 | PHASE2 | COMPLETED | A Study Of Deoxycoformycin(DCF)/Pentostatin In Lymphoid Malignancies |
| NCT00045305 | PHASE2 | COMPLETED | Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes |
| NCT00049413 | PHASE2 | COMPLETED | Combination Chemotherapy and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma |
| NCT00057954 | PHASE2 | TERMINATED | Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin’s or Hodgkin’s Lymphoma |
| NCT00074035 | PHASE2 | COMPLETED | Pentostatin in Treating Patients With Refractory Chronic Graft-Versus-Host Disease |
| NCT00074282 | PHASE2 | COMPLETED | Pentostatin, Cyclophosphamide, and Rituximab Followed By Campath-1H in Patients With Relapsed or Refractory B-Cell CLL |
| NCT00096161 | PHASE2 | COMPLETED | Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant |
| NCT00144430 | PHASE2 | COMPLETED | Pentostatin for High Risk and Refractory Chronic Graft Versus Host Disease in Children |
| NCT00201721 | PHASE2 | COMPLETED | Pentostatin, and Rituximab With and Without Cyclophosphamide for Previously Untreated B-Chronic Lymphocytic Leukemia |
| NCT00201786 | PHASE2 | COMPLETED | Phase II Trial of Pentostatin in Steroid Refractory Acute Graft Versus Host Disease |
| NCT00224874 | PHASE2 | COMPLETED | Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302) |
| NCT00402714 | PHASE2 | COMPLETED | A Trial of Extracorporeal Photopheresis, Pentostatin, and Total Body Irradiation in Patients Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation for the Treatment of Malignancies |
| NCT00453193 | PHASE2 | TERMINATED | Alemtuzumab and Pentostatin In T-cell Neoplasms |
| NCT00496340 | PHASE2 | COMPLETED | Phase II Trial of Pentostatin and Targeted Busulfan |
| NCT00496873 | PHASE2 | COMPLETED | Evaluation of the Safety and Efficacy of Nipent, Cytoxan, and Rituxan |
| NCT00506922 | PHASE1/PHASE2 | COMPLETED | Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After MUD BMT |
| NCT00541034 | PHASE2 | COMPLETED | Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia |
| NCT00546377 | PHASE1/PHASE2 | COMPLETED | Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer |
| NCT00571662 | PHASE2 | COMPLETED | Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant |
| NCT00602836 | PHASE2 | COMPLETED | Rituximab, Pentostatin, Cyclophosphamide, and Lenalidomide in Treating Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma |
| NCT00669318 | PHASE2 | COMPLETED | Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma |
| NCT00698685 | PHASE2 | TERMINATED | Pentostatin and Alemtuzumab as a Preparative Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation |
| NCT00816413 | PHASE1/PHASE2 | WITHDRAWN | Donor Stem Cell Transplant, Pentostatin, and Total-Body Irradiation in Treating Patients With Hematological Cancer |
| NCT00816595 | PHASE2 | COMPLETED | Pentostatin, Cyclophosphamide, and Rituximab With or Without Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma |
| NCT00915850 | PHASE1/PHASE2 | UNKNOWN | Trial of Docetaxel, Cisplatin, Fluorouracil (5-FU) for Unresectable Advanced Esophageal Squamous Cell Carcinoma (ESCC) |
| NCT00923845 | PHASE2 | COMPLETED | Low-Intensity Stem Cell Transplantation With Multiple Lymphocyte Infusions to Treat Advanced Kidney Cancer |
| NCT00927797 | PHASE2 | UNKNOWN | Interventional Study on Pentostatin, Cyclophosphamide and Rituximab in Indolent B-Cell Non-Hodgkin-Lymphoma (B-NHL) |
| NCT01024010 | PHASE2 | COMPLETED | Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma |
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 |
|---|---|---|---|
| AFAMELANOTIDE | ChEMBL | Phase 4 (approved) | ADA |
| COFORMYCIN | ChEMBL | Phase 2 | ADA |
| Adenosine | PubChem | Approved | ADA |
| Gs-441524 | PubChem | Approved | ADA |
Related Atlas pages
- Genes: ADA
- Diseases: neoplasm, hairy cell leukemia, anemia, B-cell chronic lymphocytic leukemia, graft versus host disease
- Drugs: Afamelanotide, Adenosine