The invention relates generally to pyrrolobenzodiazepine monomer and dimer prodrugs having a glutathione-activated disulfide prodrug moiety, a DT-diaphorase-activated quinone prodrug moiety or a reactive oxygen species-activated aryl boronic acid or aryl boronic ester prodrug moiety. The invention further relates to pyrrolobenzodiazepine prodrug dimer-antibody conjugates.

The invention relates generally to pyrrolobenzodiazepine monomer and dimer prodrugs having a glutathione-activated disulfide prodrug moiety, a DT-diaphorase-activated quinone prodrug moiety or a reactive oxygen species-activated aryl boronic acid or aryl boronic ester prodrug moiety. The invention further relates to pyrrolobenzodiazepine prodrug dimer-antibody conjugates.

The present invention relates in part to the discovery that benzodiazepines can be used to reactivate latent HIV-1 virus that is integrated into human genome. In other embodiments, the benzodiazepine is used in combination with a histone deacetylase inhibitor (HDACi), such as but not limited to SAHA (also known as N-hydroxy-N-phenyl-octanediamide, Suberoylanilide hydroxamic acid, Vorinostat). In yet other embodiments, the combination of benzodiazepine and the HDACi synergistically reactivates latent HIV-1 virus that is integrated into human genome, with minimal or no significant toxicity associated with the dose of either agent.

The present invention relates in part to the discovery that benzodiazepines can be used to reactivate latent HIV-1 virus that is integrated into human genome. In other embodiments, the benzodiazepine is used in combination with a histone deacetylase inhibitor (HDACi), such as but not limited to SAHA (also known as N-hydroxy-N-phenyl-octanediamide, Suberoylanilide hydroxamic acid, Vorinostat). In yet other embodiments, the combination of benzodiazepine and the HDACi synergistically reactivates latent HIV-1 virus that is integrated into human genome, with minimal or no significant toxicity associated with the dose of either agent.

The present invention relates to the use of an agent that inhibits the activity of an enzyme that mediates repair of a DNA strand break in the manufacture of a medicament for the treatment of diseases caused by a defect in a gene that mediates homologous recombination.

The present invention relates to the use of an agent that inhibits the activity of an enzyme that mediates repair of a DNA strand break in the manufacture of a medicament for the treatment of diseases caused by a defect in a gene that mediates homologous recombination.

The present invention provides a liquid pharmaceutical composition comprising a therapeutic agent and an alkoxy-polyethylene glycol, for example, methoxy-polyethylene glycol, for administration of the therapeutic agent to the mammal. The compositions can be applied to a membrane, for example, a nasal membrane during intranasal administration. The invention also provides methods of administering such compositions to a mammal.

The present invention provides a liquid pharmaceutical composition comprising a therapeutic agent and an alkoxy-polyethylene glycol, for example, methoxy-polyethylene glycol, for administration of the therapeutic agent to the mammal. The compositions can be applied to a membrane, for example, a nasal membrane during intranasal administration. The invention also provides methods of administering such compositions to a mammal.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.