Details
Stereochemistry | ACHIRAL |
Molecular Formula | C9H16ClN3O2 |
Molecular Weight | 233.6955 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C1CCC(CC1)N=C(N(CCCl)N=O)O
InChI
InChIKey=GQYIWUVLTXOXAJ-UHFFFAOYSA-N
InChI=1S/C9H16ClN3O2/c10-6-7-13(12-15)9(14)11-8-4-2-1-3-5-8/h8H,1-7H2,(H,11,14)
DescriptionCurator's Comment:: description was created based on several sources, including:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7f77526b-4c40-409c-82ea-d0f934d89cc2
Curator's Comment:: description was created based on several sources, including:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7f77526b-4c40-409c-82ea-d0f934d89cc2
Lomustine is used in the treatment of certain neoplastic diseases. Although it is generally agreed that lomustine alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins. Common adverse reactions include delayed myelosupression, nausea, vomiting, stomatitis, and alopecia.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2311221 |
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Target ID: CHEMBL2311222 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | GLEOSTINE Approved UseCeeNU has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following: Brain tumors—both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures. Hodgkin’s disease—secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy. Launch Date2.07964799E11 |
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Primary | GLEOSTINE Approved UseCeeNU has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following: Brain tumors—both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures. Hodgkin’s disease—secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy. Launch Date2.07964799E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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8.6 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3966974 |
20 mg/kg single, oral dose: 20 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
LOMUSTINE plasma | Mus musculus population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
2 ng/mL |
100 mg/m² single, oral dose: 100 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
LOMUSTINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
705 μg × min/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3966974 |
20 mg/kg single, oral dose: 20 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
LOMUSTINE plasma | Mus musculus population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
50% |
LOMUSTINE plasma | Homo sapiens |
Doses
Dose | Population | Adverse events |
---|---|---|
400 mg/m2 single, oral Highest studied dose Dose: 400 mg/m2 Route: oral Route: single Dose: 400 mg/m2 Co-administed with:: etoposide, i.v(1 g/m2) Sources: ara-C, i.v(4g/m2) melphalan(140 mg/m2) |
unhealthy, 36 n = 2 Health Status: unhealthy Condition: Lymphoma Age Group: 36 Population Size: 2 Sources: |
DLT: Gastrointestinal toxicity, Sinusoidal obstruction syndrome... Dose limiting toxicities: Gastrointestinal toxicity (grade 4, 50%) Sources: Sinusoidal obstruction syndrome (grade 4, 50%) |
300 mg/m2 single, oral MTD Dose: 300 mg/m2 Route: oral Route: single Dose: 300 mg/m2 Co-administed with:: etoposide, i.v(1 g/m2) Sources: ara-C, i.v(4g/m2) melphalan(140 mg/m2) |
unhealthy, 36 n = 6 Health Status: unhealthy Condition: Lymphoma Age Group: 36 Population Size: 6 Sources: |
DLT: Neurotoxicity... Dose limiting toxicities: Neurotoxicity (grade 4, 33.3%) Sources: |
130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
Disc. AE: Myelosuppression, Pulmonary toxicity... AEs leading to discontinuation/dose reduction: Myelosuppression (grade 5) Sources: Page: p.1Pulmonary toxicity Pulmonary fibrosis Acute leukemia Myelodysplasia Hepatotoxicity Nephrotoxicity Fetal damage |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Gastrointestinal toxicity | grade 4, 50% DLT |
400 mg/m2 single, oral Highest studied dose Dose: 400 mg/m2 Route: oral Route: single Dose: 400 mg/m2 Co-administed with:: etoposide, i.v(1 g/m2) Sources: ara-C, i.v(4g/m2) melphalan(140 mg/m2) |
unhealthy, 36 n = 2 Health Status: unhealthy Condition: Lymphoma Age Group: 36 Population Size: 2 Sources: |
Sinusoidal obstruction syndrome | grade 4, 50% DLT |
400 mg/m2 single, oral Highest studied dose Dose: 400 mg/m2 Route: oral Route: single Dose: 400 mg/m2 Co-administed with:: etoposide, i.v(1 g/m2) Sources: ara-C, i.v(4g/m2) melphalan(140 mg/m2) |
unhealthy, 36 n = 2 Health Status: unhealthy Condition: Lymphoma Age Group: 36 Population Size: 2 Sources: |
Neurotoxicity | grade 4, 33.3% DLT |
300 mg/m2 single, oral MTD Dose: 300 mg/m2 Route: oral Route: single Dose: 300 mg/m2 Co-administed with:: etoposide, i.v(1 g/m2) Sources: ara-C, i.v(4g/m2) melphalan(140 mg/m2) |
unhealthy, 36 n = 6 Health Status: unhealthy Condition: Lymphoma Age Group: 36 Population Size: 6 Sources: |
Acute leukemia | Disc. AE | 130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
Fetal damage | Disc. AE | 130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
Hepatotoxicity | Disc. AE | 130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
Myelodysplasia | Disc. AE | 130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
Nephrotoxicity | Disc. AE | 130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
Pulmonary fibrosis | Disc. AE | 130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
Pulmonary toxicity | Disc. AE | 130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
Myelosuppression | grade 5 Disc. AE |
130 mg/m2 1 times / 6 weeks multiple, oral Recommended Dose: 130 mg/m2, 1 times / 6 weeks Route: oral Route: multiple Dose: 130 mg/m2, 1 times / 6 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Brain tumors|Hodgkin’s lymphoma Sources: Page: p.1 |
PubMed
Title | Date | PubMed |
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APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis. | 2001 Apr |
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Adenovirus-mediated expression of HSV1-TK or Fas ligand induces cell death in primary human glioma-derived cell cultures that are resistant to the chemotherapeutic agent CCNU. | 2001 Aug |
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Chemotherapy for the treatment of oligodendroglial tumors. | 2001 Aug |
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Melanoma-associated retinopathy: does autoimmunity prolong survival? | 2001 Aug |
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PCV for oligodendroglial tumors: in search of prognostic factors for response and survival. | 2001 Aug |
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Thyroid dysfunction as a late effect in childhood medulloblastoma: a comparison of hyperfractionated versus conventionally fractionated craniospinal radiotherapy. | 2001 Aug 1 |
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Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics. | 2001 Aug-Oct |
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Adults with newly diagnosed high-grade gliomas. | 2001 Dec |
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Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia. | 2001 Feb 15 |
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Multiple myeloma in elderly patients: presenting features and outcome. | 2001 Jan |
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Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma. | 2001 Jul |
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Protection of hematopoietic cells from O(6)-alkylation damage by O(6)-methylguanine DNA methyltransferase gene transfer: studies with different O(6)-alkylating agents and retroviral backbones. | 2001 Jul |
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Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer. | 2001 Jun |
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Death receptor-independent cytochrome c release and caspase activation mediate thymidine kinase plus ganciclovir-mediated cytotoxicity in LN-18 and LN-229 human malignant glioma cells. | 2001 Mar |
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Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy. | 2001 May 1 |
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Lipid association improves the therapeutic index of lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea] to suppress 36B-10 tumor growth in rats. | 2001 May 1 |
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Pilot evaluation of 1p and 19q deletions in anaplastic oligodendrogliomas collected by a national cooperative cancer treatment group. | 2001 Oct |
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Medical Research Council adjuvant trial in high-grade gliomas. | 2001 Oct 1 |
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Nitric oxide and free stable nitroxyl radicals in the mechanism of biological action of the spin-labeled compounds. | 2001 Sep |
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[Role of adjuvant chemotherapy in the treatment of medulloblastoma in children]. | 2002 |
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11q23 balanced chromosome aberrations in treatment-related myelodysplastic syndromes and acute leukemia: report from an international workshop. | 2002 Apr |
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Treatment of advanced neuroendocrine tumours using combination chemotherapy with lomustine and 5-fluorouracil. | 2002 Aug |
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Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. | 2002 Aug 1 |
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Pulmonary complications in survivors of childhood and adolescent cancer. A report from the Childhood Cancer Survivor Study. | 2002 Dec 1 |
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Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma. | 2002 Dec 1 |
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Long-term follow-up in managing anaplastic astrocytoma by multimodality approach with surgery followed by postoperative radiotherapy and PCV-chemotherapy: phase II trial. | 2002 Jun |
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Prevention of irradiation-induced glioma cell invasion by temozolomide involves caspase 3 activity and cleavage of focal adhesion kinase. | 2002 Mar 15 |
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[Chemo-radiotherapy for malignant brain tumors]. | 2002 May |
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Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas. | 2002 May 1 |
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Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma. | 2002 May 1 |
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Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial. | 2002 Oct 1 |
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Complete response of a recurrent, multicentric malignant glioma in a patient treated with phenylbutyrate. | 2002 Sep |
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Radiotherapy alone for lymphocyte-predominant Hodgkin's disease. | 2002 Sep-Oct |
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Low-dose continuous chemotherapy for metastatic melanoma: a phase II trial. | 2003 Apr |
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Feasibility and toxicity of CCNU therapy in elderly patients with glioblastoma multiforme. | 2003 Feb |
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Survival with dacarbazine and fotemustine in newly diagnosed glioblastoma multiforme. | 2003 Feb 24 |
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Phase I study of temozolamide (TMZ) combined with procarbazine (PCB) in patients with gliomas. | 2003 Jul 21 |
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Myeloid clonogenic assays for comparison of the in vitro toxicity of alkylating agents. | 2003 Jun |
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High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy. | 2003 Jun 15 |
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Glioma treatment, radionecrosis, and growth factors. In regard to Levin et al., IJROBP 2002;53:58-66. | 2003 Mar 1 |
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Interobserver variability in the radiological assessment of response to chemotherapy in glioma. | 2003 Mar 11 |
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Combined modality therapy for poorly differentiated gliomas of the posterior fossa in children: a Children's Cancer Group report. | 2003 May |
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Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. | 2003 May |
Sample Use Guides
In Vivo Use Guide
Curator's Comment:: Lomustine is available in 5 mg, 10 mg, 40 mg, and 100 mg capsules.
In individuals with compromised bone marrow function, the dose should be reduced to 100 mg/m2 every 6 weeks.
Recommended dose in adult and pediatric patients is 130 mg/m2 orally every 6 weeks.
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/6228232
Curator's Comment:: A single dose of Lomustine (40 mg/kg) caused a significant reduction in hepatic mixed-function oxidase activities within 3 days after administration
http://www.ncbi.nlm.nih.gov/pubmed/6722931
Alkylation of the nuclear matrix by Lomustine was 1.27 pmoles drug/micrograms protein, whereas carbamoylation by Lomustine was 32.5 pmoles/micrograms.
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Classification Tree | Code System | Code | ||
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LIVERTOX |
566
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NCI_THESAURUS |
C699
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NDF-RT |
N0000000236
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WHO-VATC |
QL01AD02
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WHO-ATC |
L01AD02
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NDF-RT |
N0000175558
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SUB08567MIG
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13010-47-4
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M6891
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3950
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13010-47-4
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1596
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6466
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6519
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LOMUSTINE
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D008130
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7214
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C617
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DB01206
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1369419
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235-859-2
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3184
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7BRF0Z81KG
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CHEMBL514
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ACTIVE MOIETY