Lomustine

Catalog No.S1840 Synonyms: nsc79037

Lomustine  Chemical Structure

Molecular Weight(MW): 233.7

Lomustine inhibits cancer cells by damaging the DNA and stops cells from dividing.

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1 Customer Review

  • Initial range finding concentration response analysis of the cytotoxic effects of (A) lomustine (IC50 = 12 μM) and (B) vincristine (IC50 = 1.5 nM) on D283 Med in a clonogenic assay of cell survival

    biorxiv, 2017. Lomustine purchased from Selleck.

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Biological Activity

Description Lomustine inhibits cancer cells by damaging the DNA and stops cells from dividing.
Features A more specific and potent anti-medulloblastoma agent compared to Vincristine.
In vitro

Lomustine inhibits the growth of ZR-75-1 and U373 with IC50 of 12 μM and 15 μM, respectively. Lomustine reduces the level of expression of the DNA repair protein O6-alkylguanine-DNA alkyltransferase. [1] Lomustine (420 μM) triggers apoptosis through the mitochondrial pathway via decrease in the level of the anti-apoptosis proteins Bcl-2 and Bcl-xl, respectively, in both medulloblastoma and normal human epithelial and fibroblast cells. Lomustine induces cell cycle delay in G2/M phase in medulloblastoma cells and up-regulates p21 protein level in a p53-independent manner in HFSN1 cells. [2]

In vivo Lomustine can cause delayed, cumulative dose-related, chronic hepatotoxicity that is irreversible and can be fatal. [4] Lomustine could result in infrequent severe hematological toxicity in cats with spontaneously arising tumors, and the incidence of either grade III or IV neutropenia and thrombocytopenia is 4.1% and 1.0%, respectively. Lomustine trends toward a greater likelihood for progressive neutropenia and statistically significant higher response rates in cats with spontaneously arising tumors. [5]

Protocol

Cell Research:[1]
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  • Cell lines: XP cells
  • Concentrations: 133 μM
  • Incubation Time: 1 hour
  • Method: Cell lines are routinely grown as monolayers in DMEM supplemented with 10% foetal calf serum, 25 mm HEPES, glutamine and penicillin/streptomycin. Cytotoxicity studies are carried out in HEPES-free medium in a 5% CO2 atmosphere. 750-1000 cells/well are plated in 96 well plates and after overnight incubation are treated for 2 hours with or without 33 μM BG. Temozolomide or CCNU is then added for 1 hour in the same medium, the final DMSO concentration not exceeding 1%. The cells are grown for a further 7 days in fresh medium and assayed for protein content by the NCI sulphorhodamine assay; growth studies show that cells are in log phase growth during the assay period. For the repeat temozolomide dosing schedule cells are given consecutive 24 hours treatments, with fresh medium each day. Assays are carried out at least in duplicate.
    (Only for Reference)
Animal Research:[3]
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  • Animal Models: Dogs
  • Formulation: Saline
  • Dosages: 90 mg/m2
  • Administration: Orally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 46 mg/mL (196.83 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
30% propylene glycol, 5% Tween 80, 65% D5W, pH 4
10 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 233.7
Formula

C9H16ClN3O2

CAS No. 13010-47-4
Storage powder
Synonyms nsc79037

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03022578 Not yet recruiting Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System|Glioblastoma|Anaplastic Astrocytoma M.D. Anderson Cancer Center|Monteris Medical May 2017 Phase 2
NCT02986178 Not yet recruiting Malignant Glioma Darell D. Bigner, MD, PhD|Duke University March 2017 Phase 2
NCT03025893 Not yet recruiting Glioblastoma Multiforme|Glioblastoma, Adult|Glioblastoma|Recurrent Brain Tumor|GBM VU University Medical Center March 2017 Phase 2|Phase 3
NCT02724579 Not yet recruiting Untreated Childhood Medulloblastoma Childrens Oncology Group|National Cancer Institute (NCI) October 2016 Phase 2
NCT01775475 Recruiting AIDS-related Diffuse Large Cell Lymphoma|AIDS-related Diffuse Mixed Cell Lymphoma|AIDS-related Diffuse Small Cleaved Cell Lymphoma|AIDS-related Immunoblastic Large Cell Lymphoma|AIDS-related Lymphoblastic Lymphoma|AIDS-related Peripheral/Systemic Lymphoma|AIDS-related Small Noncleaved Cell Lymphoma|Stage III AIDS-related Lymphoma|Stage IV AIDS-related Lymphoma AIDS Malignancy Consortium|National Cancer Institute (NCI)|The EMMES Corporation September 2016 Phase 2
NCT02843230 Not yet recruiting Glioblastoma Massachusetts General Hospital August 2016 --

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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DNA/RNA Synthesis Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID