Disclosed in certain embodiments is a solid oral dosage form comprising a heat-labile gelling agent; a thermal stabilizer; and a drug susceptible to abuse.

Disclosed in certain embodiments is a solid oral dosage form comprising a heat-labile gelling agent; a thermal stabilizer; and a drug susceptible to abuse.

N-(furan-2-ylmethyl)-7H-purin-6-amine, or a pharmaceutically acceptable salt or solvate thereof, for prevention and/or treatment of circadian rhythm disorders, circadian rhythm diseases and/or circadian rhythm dysfunctions is disclosed. The disorders, diseases and dysfunctions include, inter alia, jet-lag, social jet-lag, shift-work disorder, and circadian rhythm disturbance induced by neurodegeneration is also disclosed.

N-(furan-2-ylmethyl)-7H-purin-6-amine, or a pharmaceutically acceptable salt or solvate thereof, for prevention and/or treatment of circadian rhythm disorders, circadian rhythm diseases and/or circadian rhythm dysfunctions is disclosed. The disorders, diseases and dysfunctions include, inter alia, jet-lag, social jet-lag, shift-work disorder, and circadian rhythm disturbance induced by neurodegeneration is also disclosed.

The present invention provides a combination and method for treating a Temozolomide (TMZ)-resistant cancer patient, which comprises a combination of TMZ and an isoform-selective HDAC8 inhibitor, such as BMX at an effective relative ratio to overcome TMZ resistance by enhancing TMZ-mediated cytotoxic effect by downregulating the β-catenin/c-Myc/SOX2 signaling pathway and upregulating WT-p53 mediated MGMT inhibition.

The present invention provides a combination and method for treating a Temozolomide (TMZ)-resistant cancer patient, which comprises a combination of TMZ and an isoform-selective HDAC8 inhibitor, such as BMX at an effective relative ratio to overcome TMZ resistance by enhancing TMZ-mediated cytotoxic effect by downregulating the β-catenin/c-Myc/SOX2 signaling pathway and upregulating WT-p53 mediated MGMT inhibition.

Neuroinflammation mediated by microglia and infiltrating peripheral immune cells is a major component of stroke pathophysiology. The calcium activated potassium channel K.sub.Ca3.1 is expressed selectively in the injured CNS by microglia, and K.sub.Ca3.1 function has been implicated in proinflammatory activation of microglia. K.sub.Ca3.1 is further implicated in the pathophysiology of ischemia/reperfusion (stroke) related brain injury. Senicapoc, an investigational drug with a proven safety profile and shown to cross the blood-brain barrier, is a potent and selective K.sub.Ca3.1 inhibitor that intervenes in the inflammation cascade that follows ischemia/reperfusion, and is a potential treatment for stroke.

Neuroinflammation mediated by microglia and infiltrating peripheral immune cells is a major component of stroke pathophysiology. The calcium activated potassium channel K.sub.Ca3.1 is expressed selectively in the injured CNS by microglia, and K.sub.Ca3.1 function has been implicated in proinflammatory activation of microglia. K.sub.Ca3.1 is further implicated in the pathophysiology of ischemia/reperfusion (stroke) related brain injury. Senicapoc, an investigational drug with a proven safety profile and shown to cross the blood-brain barrier, is a potent and selective K.sub.Ca3.1 inhibitor that intervenes in the inflammation cascade that follows ischemia/reperfusion, and is a potential treatment for stroke.

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.