Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours
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چکیده
منابع مشابه
Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours
BACKGROUND Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG200...
متن کاملSJG-136 (NSC 694501), a novel rationally designed DNA minor groove interstrand cross-linking agent with potent and broad spectrum antitumor activity: part 2: efficacy evaluations.
Pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136 (NSC 694501) selectively cross-links guanine residues located on opposite strands of DNA, and exhibits potent in vitro cytotoxicity. In addition, SJG-136 is highly active in vivo in hollow fiber assays. In the current investigation, SJG-136 was evaluated for in vivo efficacy in 10 tumor models selected on the basis of sensitivity of cells grown in...
متن کاملSequence-selective interaction of the minor-groove interstrand cross-linking agent SJG-136 with naked and cellular DNA: footprinting and enzyme inhibition studies.
SJG-136 (3) is a novel pyrrolobenzodiazepine (PBD) dimer that is predicted from molecular models to bind in the minor groove of DNA and to form sequence-selective interstrand cross-links at 5'-Pu-GATC-Py-3' (Pu = purine; Py = pyrimidine) sites through covalent bonding between each PBD unit and guanines on opposing strands. Footprinting studies have confirmed that high-affinity adducts do form a...
متن کاملPhase I pharmacokinetic and pharmacodynamic study of SJG-136, a novel DNA sequence selective minor groove cross-linking agent, in advanced solid tumors.
PURPOSE This phase I study assessed the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SJG-136, a sequence-specific DNA cross-linking agent, in patients with advanced cancer. EXPERIMENTAL DESIGN In schedule A, seven patients received escalating doses of SJG-136 (6, 12, 24, and 48 μg/m(2)) daily for 5 of 21 days. Blood samples were colle...
متن کاملPhase I study of sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors.
PURPOSE This phase I dose-escalation study was undertaken to establish the maximum tolerated dose of the sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors. The study also investigated antitumor activity and provided pharmacokinetic and pharmacodynamic data. EXPERIMENTAL DESIGN Sixteen patients were assigned sequentially to escalating doses of SJG...
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ژورنال
عنوان ژورنال: BMC Veterinary Research
سال: 2015
ISSN: 1746-6148
DOI: 10.1186/s12917-015-0534-2