Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C10H12ClN5O3 |
Molecular Weight | 285.687 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC(Cl)=NC2=C1N=CN2[C@H]3C[C@H](O)[C@@H](CO)O3
InChI
InChIKey=PTOAARAWEBMLNO-KVQBGUIXSA-N
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
Molecular Formula | C10H12ClN5O3 |
Molecular Weight | 285.687 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: Description was created using several sources including:
https://www.scripps.edu/newsandviews/e_20090601/MS.html; http://comtecmed.com/CONY/2008/Uploads/assets/speakers%20abstracts/stelmasiak.pdf
Curator's Comment: Description was created using several sources including:
https://www.scripps.edu/newsandviews/e_20090601/MS.html; http://comtecmed.com/CONY/2008/Uploads/assets/speakers%20abstracts/stelmasiak.pdf
Cladribine is used for the treatment of hairy cell leukemia and multiple sclerosis (MS). As a purine analog, it is a synthetic anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It can be distinguished from other chemotherapeutic agents affecting purine metabolism in that it is cytotoxic to both actively dividing and quiescent lymphocytes and monocytes, inhibiting both DNA synthesis and repair. Cladribine injection is a potent antineoplastic agent with potentially significant toxic side effects. In MS, the novel mechanism of action of cladribine is expected to reduce inflammation, autoimmune effects and autoreactive cell damage, thereby improving the integrity of the blood–brain barrier. Thus, the effects of cladribine may target some of the key events that are central to the pathophysiology of MS.
CNS Activity
Sources: http://multiple-sclerosis-research.blogspot.com/2016/01/the-special-one-cladribine-acting-in-cns.html
Curator's Comment: As cladribine can cross the blood brain barrier and can kill dividing and non-dividing T and B cells and can apparently kill plasma cells. It could target plasma cells in the brain, unlike any other MS drug.
Originator
Curator's Comment: The drug, cladribine, which is currently marketed under the name LEUSTATIN® by Ortho Biotech, Inc. (an affiliate of Johnson & Johnson) for the treatment of hairy cell leukemia, was initially identified and developed using a single treatment of the new compound to target abnormal white blood cells in patients suffering from hairy cell leukemia by Dennis Carson in collaboration with Ernest Beutler a Scripps Research scientists who licensed caldribine as an orphan drug in 1994. Merck Serono's CLARITY study, involving 1326 Multiple Sclerosis patients, began in 2004 and was completed in December 2008.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P06746 Gene ID: 5423.0 Gene Symbol: POLB Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=20634380 |
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Target ID: CHEMBL2311221 Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=20634380 |
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Target ID: P23526 Gene ID: 191.0 Gene Symbol: AHCY Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=20634380 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | CLADRIBINE Approved Usethe treatment of active Hairy Cell Leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia or disease-related symptoms. Launch Date1995 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
20.57 ng/mL |
3 mg single, intravenous dose: 3 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLADRIBINE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
29.05 ng/mL |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLADRIBINE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
69.4 ng × h/mL |
3 mg single, intravenous dose: 3 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLADRIBINE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
99.17 ng × h/mL |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLADRIBINE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
18.4 h |
3 mg single, intravenous dose: 3 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
CLADRIBINE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
19.7 h |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
CLADRIBINE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
5.25 mg/kg multiple, oral (total) Highest studied dose Dose: 5.25 mg/kg Route: oral Route: multiple Dose: 5.25 mg/kg Sources: Page: p.262 |
unhealthy, ADULT n = 204 Health Status: unhealthy Condition: multiple sclerosis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 204 Sources: Page: p.262 |
Disc. AE: Lymphopenia... AEs leading to discontinuation/dose reduction: Lymphopenia (grade 3-4) Sources: Page: p.262 |
8 mg/m2 1 times / day multiple, intravenous MTD Dose: 8 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 8 mg/m2, 1 times / day Sources: Page: p.170 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.170 |
DLT: Neutropenia, Leukopenia... Dose limiting toxicities: Neutropenia (grade 4, 50%) Sources: Page: p.170Leukopenia (grade 4, 50%) |
0.07 mg/kg 1 times / day multiple, subcutaneous Studied dose Dose: 0.07 mg/kg, 1 times / day Route: subcutaneous Route: multiple Dose: 0.07 mg/kg, 1 times / day Sources: Page: p.1152 |
unhealthy, ADULT n = 52 Health Status: unhealthy Condition: multiple sclerosis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 52 Sources: Page: p.1152 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Lymphopenia | grade 3-4 Disc. AE |
5.25 mg/kg multiple, oral (total) Highest studied dose Dose: 5.25 mg/kg Route: oral Route: multiple Dose: 5.25 mg/kg Sources: Page: p.262 |
unhealthy, ADULT n = 204 Health Status: unhealthy Condition: multiple sclerosis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 204 Sources: Page: p.262 |
Leukopenia | grade 4, 50% DLT |
8 mg/m2 1 times / day multiple, intravenous MTD Dose: 8 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 8 mg/m2, 1 times / day Sources: Page: p.170 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.170 |
Neutropenia | grade 4, 50% DLT |
8 mg/m2 1 times / day multiple, intravenous MTD Dose: 8 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 8 mg/m2, 1 times / day Sources: Page: p.170 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.170 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ |
no | |||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ |
no | |||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/29987837/ |
no | |||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
[Lupus nephritis: treatments for today and tomorrow]. | 2001 |
|
Flow cytometry of peripheral blood and bone marrow cells from patients with hairy cell leukemia: phenotype of hairy cells, lymphocyte subsets and detection of minimal residual disease after treatment. | 2001 |
|
Cladribine combined with mitoxantrone in the treatment of blastic phase of chronic myeloid leukemia. | 2001 |
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Infectious complications of purine analog therapy. | 2001 Aug |
|
Richter's syndrome following cladribine therapy for chronic lymphocytic leukemia first manifested as pathologic fracture of the femur. | 2001 Aug |
|
Effect of cladribine treatment on beta-2 microglobulin and soluble intercellular adhesion molecule 1 (ICAM-1) in patients with multiple sclerosis. | 2001 Aug |
|
A phase II study of sequential combination chemotherapy with cyclophosphamide, prednisone, and 2-chlorodeoxyadenosine in previously untreated patients with chronic lymphocytic leukemia. | 2001 Aug |
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Sin of omission? Pharmaceutical trade group failed to disclose that ad subject was employee. | 2001 Aug 6 |
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Successful treatment of refractory Langerhans cell histiocytosis with unrelated cord blood transplantation. | 2001 Dec |
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Cladribine. Ortho Biotech Inc. | 2001 Dec |
|
Hematological effects of intermittent 2-hour infusions of cladribine in multiple sclerosis patients: a comparison of 2 dosage patterns. | 2001 Dec |
|
Gynecomastia in a case of hairy cell leukaemia--cladribine induced? | 2001 Jun |
|
Treatment options in Waldenström's macroglobulinaemia: the role of the purine analogues. | 2001 Jun |
|
Nucleoside analogues in the treatment of haematological malignancies. | 2001 Jun |
|
Immunologic therapy for secondary and primary progressive multiple sclerosis. | 2001 May |
|
Prolymphocytic leukemia or prolymphocytic transformation of mantle cell lymphoma. | 2001 Nov |
|
Resistance to 2-chloro-2'-deoxyadenosine of the human B-cell leukemia cell line EHEB. | 2001 Nov |
|
Acquisition of human concentrative nucleoside transporter 2 (hcnt2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells. | 2001 Nov |
|
Cladribine induces apoptosis in human leukaemia cells by caspase-dependent and -independent pathways acting on mitochondria. | 2001 Nov 1 |
|
Treatment of hairy-cell leukemia. | 2001 Nov 15 |
|
Plasmablastic lymphoma in a patient with chronic lymphocytic leukemia heavily pretreated with cladribine (2-CdA): an unusual variant of Richter's syndrome. | 2001 Nov-Dec |
|
Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia. | 2001 Oct |
|
Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia. | 2001 Oct |
|
[Recent progress in the treatment of malignant lymphoma]. | 2001 Sep |
|
Impact of treatment on the outcome of acute myeloid leukemia with inversion 16: a single institution's experience. | 2001 Sep |
|
Exposure-disease continuum for 2-chloro-2'-deoxyadenosine, a prototype ocular teratogen. 1. Dose-response analysis. | 2001 Sep |
|
In vitro release of cytotoxic nucleoside analogs from lactide-caprolactone and lactide-glycolide copolymers. | 2002 |
|
Immunosuppression with limited toxicity: the characteristics of nucleoside analogs and anti-lymphocyte antibodies used in non-myeloablative hematopoietic cell transplantation. | 2002 |
|
Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma. | 2002 Apr |
|
[Hairy cell leukemia treated with cladribine]. | 2002 Apr 30 |
|
Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association? | 2002 Aug |
|
Specificity of human and rat orthologs of the concentrative nucleoside transporter, SPNT. | 2002 Aug |
|
Cladribine underdosing in hairy-cell leukemia: a cause for apparent response failure. | 2002 Feb |
|
Therapeutic approaches to secondary progressive multiple sclerosis. | 2002 Feb |
|
Suspected delayed immune recovery against cytomegalovirus after reduced-intensity stem cell transplantation using anti-thymocyte globulin. | 2002 Feb |
|
Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing-Neel syndrome: Case report and review of the literature. | 2002 Feb |
|
Use of 2-chlorodeoxyadenosine to treat infantile myofibromatosis. | 2002 Jan |
|
2-Chloro-2'-deoxyadenosine inhibits DNA repair synthesis and potentiates UVC cytotoxicity in chronic lymphocytic leukemia B lymphocytes. | 2002 Jan |
|
Cladribine (2-chlorodeoxyadenosine) therapy in hairy cell leukemia variant. A report of three cases. | 2002 Jan |
|
Anti-CD20 antibody (IDEC-C2B8, rituximab) enhances efficacy of cytotoxic drugs on neoplastic lymphocytes in vitro: role of cytokines, complement, and caspases. | 2002 Jan |
|
Resistance of leukemic cells to 2-chlorodeoxyadenosine is due to a lack of calcium-dependent cytochrome c release. | 2002 Jan 15 |
|
Immune response by host after allogeneic chondrocyte transplant to the cartilage. | 2002 Jul 1 |
|
Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia. | 2002 Jun |
|
Widespread skin-limited adult Langerhans cell histiocytosis: long-term follow-up with good response to interferon alpha. | 2002 Mar |
|
Treatment of children with Langerhans cell histiocytosis with 2-chlorodeoxyadenosine. | 2002 Mar |
|
Severe decrease in peripheral blood dendritic cells in hairy cell leukaemia. | 2002 Mar |
|
Oral cladribine for B-cell chronic lymphocytic leukaemia: report of a phase II trial with a 3-d, 3-weekly schedule in untreated and pretreated patients, and a long-term follow-up of 126 previously untreated patients. | 2002 Mar |
|
Cytotoxicity of 2-chlorodeoxyadenosine and arabinosylcytosine in leukaemic lymphoblasts from paediatric patients: significance of cellular nucleoside transporter content. | 2002 Mar |
|
[Therapeutic effectiveness of cladribine and cellular immunodeficiency--related effects in hairy-cell leukemia?]. | 2002 May |
|
Aggressive growth of epithelial carcinomas following treatment with nucleoside analogues. | 2002 May |
Sample Use Guides
0.09 mg/kg/day
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/24972933
Curator's Comment: The lethal dose of cytarabine for CTRL cells (Mantle cell lymphoma cell line ) ranged from 0.05 to 0.4 μM determined in In vitro cytotoxicity assay that was used to analyze cells relative responsiveness to araC (cladribine).
0.05 - 0.4 uM
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:01:30 GMT 2023
by
admin
on
Fri Dec 15 15:01:30 GMT 2023
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Record UNII |
47M74X9YT5
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C2157
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FDA ORPHAN DRUG |
54190
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FDA ORPHAN DRUG |
51690
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WHO-VATC |
QL01BB04
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EU-Orphan Drug |
EU/3/01/055
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FDA ORPHAN DRUG |
943223
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EMA ASSESSMENT REPORTS |
LITAK (AUTHORIZED: LEUKEMIA, HAIRY CELL)
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FDA ORPHAN DRUG |
467214
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LIVERTOX |
NBK548555
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FDA ORPHAN DRUG |
68092
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NCI_THESAURUS |
C1556
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FDA ORPHAN DRUG |
77793
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WHO-ATC |
L04AA40
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NCI_THESAURUS |
C798
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FDA ORPHAN DRUG |
47990
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NDF-RT |
N0000175712
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WHO-ATC |
L01BB04
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667
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Cladribine
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47M74X9YT5
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CHEMBL1619
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567361
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CLADRIBINE
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47M74X9YT5
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D017338
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44157
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DB00242
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100000085410
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4291-63-8
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DTXSID8022828
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DD-79
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SUB06635MIG
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20279
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4799
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1134200
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105014
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m3606
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6997
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C1336
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7564
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Related Record | Type | Details | ||
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR |
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR |
Related Record | Type | Details | ||
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (TLC)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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