laromustine (VNP40101M)

03/01/2012 - "Studies using tumor cell survival and tumor growth assays showed effects of regimens combining Laromustine and radiation that were compatible with additive or subadditive interactions. "
01/01/2009 - "Laromustine is currently in phase II/III trials for AML and phase II trials for MDS and solid tumors. "
07/01/2007 - "The current study was designed to assess the activity of VNP40101M administered at a dose of 18 mg/kg daily for five days against a panel of human adult and pediatric CNS tumors growing subcutaneously or intracranially in athymic nude mice. "
03/01/2005 - "A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer."
01/01/2015 - "Metabolic disposition of the anti-cancer agent [(14)C]laromustine in male rats."

12/01/2006 - "A multicenter phase II study of cloretazine was conducted in patients with first relapse of acute myeloid leukemia (AML) following an initial complete remission (CR) of less than 12 months. "
02/10/2010 - "Single-agent laromustine, a novel alkylating agent, has significant activity in older patients with previously untreated poor-risk acute myeloid leukemia."
03/01/2006 - "Cloretazine for the treatment of acute myeloid leukemia."
01/01/2007 - "A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). "
03/01/2006 - "A large Phase II study of single agent cloretazine (600 mg/m2) confirmed its activity in patients with relapsed acute myeloid leukemia, and in elderly patients with previously untreated acute myeloid leukemia or myelodysplastic syndrome. "

10/01/2009 - "Further clinical studies are required with laromustine to evaluate its place as an anticancer agent in other hematological malignancies."
10/01/2009 - "Clinical activity of laromustine (Onrigin™) in hematologic malignancies."
01/01/2009 - "Early phase I clinical trials in patients with solid tumors indicated that laromustine was associated with myelosuppression; few extramedullary toxicities were observed, indicating potential efficacy for the treatment of hematological malignancies. "
06/01/2010 - "We conducted a phase I translational study to evaluate the toxicities and estimate the maximum tolerated dose (MTD) of laromustine when administered with temozolomide (TMZ) in patients with hematologic malignancies. "

10/01/2012 - "Consistent with this design, 7 demonstrates both hypoxia selective conversion by EMT6 cells of 7 to 3 and hypoxic sensitization of AGT containing DU145 cells to the cytotoxic actions of laromustine, while exhibiting improved solubility."
03/01/2012 - "Hypoxia during Laromustine treatment did not protect EMT6 cells or human fibroblasts from this agent. "
11/10/2011 - "While 3 had little or no effect on laromustine cytotoxicity under aerobic conditions, significant enhancement occurred under oxygen deficiency, providing evidence for the preferential release of the AGT inhibitor O(6)-BG under hypoxia."
06/01/2010 - "Comparison of the cytotoxicity of KS119 in cultured cells lacking O(6)-alkylguanine-DNA alkyltransferase (AGT) to an agent such as Onrigin, which through base catalyzed activation produces the same critical DNA G-C cross-link lesions by the generation of 90CE, indicates that KS119 is substantially more potent than Onrigin under conditions of oxygen deficiency, despite being incompletely activated. "

05/01/2004 - "A Phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia."
01/01/2005 - "Flow cytometric studies using annexin as a marker for apoptosis indicate that in Chinese hamster ovary cells and in human leukemia cells Cloretazine-induced apoptosis is primarily caused by the generated methyl isocyanate. "
06/01/2010 - "Temozolomide's inhibition of AGT may sensitize leukemia cells to the novel alkylator laromustine. "
10/01/2008 - "Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species."
06/01/2007 - "The combination therapy, consisting of a single dose of 10 mg/kg Cloretazine plus five doses of 70 mg/kg fludarabine, given every other day intraperitoneally, significantly increased the long-term survival of BDF1 mice bearing the L1210 murine leukemia. "