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N-methyl-2-pyrrolidone (NMP) is a common solvent and drug vehicle. We discovered unexpected antineoplastic and immunomodulatory activity of NMP in a cMYC-driven myeloma model. Coincident to this, NMP was identified as an acetyllysine mimetic and candidate bromodomain ligand. Accordingly, NMP-treated cells demonstrated transcriptional overlap with BET-bromodomain inhibition, including downregulation of cMYC and IRF4. NMP’s immunomodulatory activity occurred at sub-BET inhibitory concentrations, and, despite phenotypic similarities to lenalidomide, its antimyeloma activity was independent of the IMiD targets cereblon and Ikaros-1/3. Thus, low-affinity yet broad-spectrum bromodomain inhibition by NMP mediates biologically potent, cereblon-independent immunomodulation and at higher doses targets malignant cells directly via BET antagonism. These data reveal that NMP is a functional acetyllysine mimetic with pleotropic antimyeloma and immunomodulatory activities. Our studies highlight the potential therapeutic benefits of NMP, the consequences of current human NMP exposures, and the need for reassessment of scientific literature where NMP was used as an “inert” drug-delivery vehicle.

This article examines the ideas of citizenship, social capital and community, and of personal and social responsibility, which have become prominent in Great Britain since the election of the Labour Government in 1997, and also in a number of other, mostly English-speaking, countries. They became especially prominent during the early summer of 2003 with the publication of the Prime Minister's Progress and Justice in the 21st Century (Blair, 2003), the Home Secretary's Civil Renewal: A New Agenda (Blunkett, 2003a), and Hazel Blears' Communities in Control: Public Services and Local Socialism (2003). The present paper reflects on the changing nature of the debate and applies the ideas of citizenship, social capital and community to the country's response to crime, to the current issues regarding the nature and purpose of criminal justice, and to the structure and accountability of the criminal justice services. It draws attention to the limitations of the criminal justice system, and of the state, in providing solutions to the range of problems connected with crime and the various forms of social disorder and unacceptable behaviour; and suggests how ideas of citizenship can help to inform social policy and professional practice, illuminate the reform of public services, and offer a sense of purpose and direction which will give vitality and legitimacy to developments in the future. [ABSTRACT FROM AUTHOR]