La presente invention concerne un systeme et un procede faisant appel a des microbes pour convertir une matiere premiere de type biomasse en carburant. Selon un aspect, un procede de production de lipides comprend les etapes consistant a utiliser une matiere premiere comprenant de la biomasse, a exposer ladite matiere premiere a des microbes capables de la convertir en lipides et a extraire les lipides ainsi produits.

Purpose Cancer chemotherapy continues to be challenged by the emergence of resistant tumors, and one organelle entwined in the development of drug resistance is the Golgi apparatus. Recently, we discovered a group of 2-(substituted phenyl)-benzimidazole (2-PB) compounds that displace resident Golgi proteins from the juxtanuclear region resulting in their degradation. These compounds are also potent anti-proliferative agents, which together with their action on the Golgi made a compelling case for testing them against cancer.Methods The anti-tumor activity of a group of 2-PB compounds was examined both in vitro and in vivo. The role of the Golgi in the anti-proliferative effect was assessed by comparing the proliferation of individual cell lines with the distribution and total cellular expression of selected resident Golgi proteins.Results The anti-proliferative activity of 2-PB compounds is partially reversible (time- and concentration-dependent), non-cell-cycle-specific, and translates to tumor growth inhibition in vivo. While 2-PB compounds displace resident Golgi proteins from the juxtanuclear region in all cells, those that are resistant to the anti-proliferative effects differ from sensitive cells in that they have the capacity to protect these Golgi proteins from degradation.Conclusions These results illustrate the utility of targeting the Golgi for cancer drug development. They also reveal a cellular strategy for resisting 2-PB drug effects through protection of displaced Golgi proteins from degradation thus allowing their continued function.

Drugs targeted to viral proteins are highly vulnerable to the development of resistant strains. We previously characterized a group of 2-phenylbenzimidazole compounds for their activity against allergy and asthma and more recently established the Golgi as their probable site of action. Herein we describe their activity against the propagation of several virus types through an action on the host cell. The most potent derivatives are the novel 2-phenylimidazopyridines, the lead compound of which is highly effective for blocking the spread of topical herpes infection in an animal model. These agents may provide an alternative antiviral approach, particularly for treating resistant strains.

The pharmacotherapy of allergy and asthma has traditionally focused on the effecter molecules of the allergic cascade, while neglecting targets that play an early role in their development. Reasoning that IgE is central to the expansion of atopic diseases, we identified and extended a novel family of 2-(substituted phenyl)-benzimidazole inhibitors of IgE response. Pharmacological activity depends on an intact phenylbenzimidazole-bis-amide backbone, and is optimized by the presence of lipophilic terminal groups composed of either bis cycloalkyl or combinations of aliphatic and halogen-substituted aromatic groups. These compounds also inhibit IL-4 and IL-5 responses in T cells and CD23 expression on B cells, with potencies that parallel their inhibition of IgE. The broad profile of these compounds thus underscores their potential for treating the multifarious pathology of asthma.

RATIONALE:We have previously shown that AVP-13358 suppresses IgE, CD23, and Th2 cytokine responses ex vivo and in vitro in mouse and human cell assays with low nM IC50s.It is also effective in vivo in models of experimental asthma following oral administration.Herein we describe recent results that outline a novel mechanism for the observed actions of AVP-13358, and present Phase I clinical trial data that shows the drug is well-tolerated following doses that provide serum exposure sufficient for therapeutic activity in mice. METHODS:The effect on protein expression (Western blotting), structure (electron microscopy), and movement (immunocytochemistry) in primary cells and tumor cells lines was evaluated following treatment with AVP-13358 or AVP-893.RESULTS: AVP compounds suppress the expression of several resident Golgi proteins over a period of 4-16 hours with potencies that parallel their suppression of IgE responses in vitro.The disappearance of these proteins is not accompanied by the loss of proteins involved in Golgi structure or from other organelles.Experimentally, the effect on resident Golgi proteins is accompanied by inhibition of glycosylation and trafficking of selected cargo proteins in a manner that is temporally consistent with inhibition of cytokine, CD23, and IgE expression.Finally, we show that the actions of AVP-893 and AVP-13358 are clearly different from that of known protein traffic perturbing agents such as brefeldin-A, monensin, or nocodazole.CONCLUSIONS: AVP-13358 is a potentially clinically important compound that suppresses experimental asthma via a mechanism that is unduplicated among compounds in development for allergy or other indications.

The effectiveness of the injectable anti-IgE antibody omalizumab has validated IgE as an important target for allergic diseases, thus spawning the development of small-molecule IgE inhibitors. Herein, a brief SAR is described for novel phenylbenzimidazole compounds that potently suppress IgE responses. In addition to IgE, these agents inhibit other targets critical for allergic response. The profile of orally active AVP-13358, the lead compound of this series currently in clinical trials, is described.