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| Anti-Infective Market The PepTx antimicrobial drugs fall into the class of bacterial membrane disintegrators. This class of antimicrobials function by integrating into the bacterial membrane and forming pores that cause the bacterial membrane to become permeable, thereby killing the bacteria. Currently, compounds in this class number in the hundreds; however, at therapeutic concentrations, most also cause extensive damage to all cells in the body, including red blood cells. In addition to the effect upon bacterial cell membranes, the PepTx drug leads bind to and neutralize the Gram negative bacterial endotoxin lipopolysaccharide (LPS). LPS is part of the Gram negative bacterial membrane and is released into the blood upon bacterial membrane lysis. LPS then triggers a cascade of events, including the production of high levels of cytokines that can lead to the clinical symptoms of sepsis and death. PTX002 PTX002 is a bpep peptide 33mer designed as an antimicrobial agent. In vitro, PTX002 is effective against a broad spectrum of bacteria, killing Gram negative bacteria in the nanomolar range and Gram positive bacteria in the sub-micromolar range. PTX002 is also able to neutralize LPS. Exemplary results are presented in Table 4. These drug leads function by disintegrating, bacterial membranes. The PTX antimicrobial "family" appears to be more potent than other members of this class of antimicrobials, viz., magainin and cecropin. Theoretically, PTX002 should not be subject to bacterial resistance, as has become common with many antimicrobials. PTX002 and a truncated version, PTX005, appear to be specific for bacterial cell membranes, as no eukaryotic cellular damage, i.e., red blood cell destruction, has been observed at millimolar concentrations, providing an early therapeutic index indication in support of tolerability in animals. The PTX antimicrobial family is currently being evaluated for performance against standard antibiotic-resistant strains of bacteria, and preliminary data appears favorable.PTX005 PTX005 is a peptide 12mer derived from bpep peptides. This peptide forms a helical structure, but maintains the same ability to specifically disintegrate bacterial membranes as PTX002. In vitro, PTX005 is more effective against several bacterial strains than PTX002. PTX005 is also able to neutralize LPS. Exemplary results are presented in Table 4.PTX006 PTX006 is a chemically-modified analog of PTX005 that displays greater activity than PTX005 at killing Gram positive bacteria in vitro, including drug resistant strains. PTX006 is also able to neutralize LPS. Exemplary results are presented in Table 4. PTX007 PTX007 is a small, non-peptidic mimetic of PTX005. This NCE molecule consists of an organic scaffold that presents key functional groups as spatially oriented in PTX005 and maintains the ability to disintegrate bacterial membranes. However, PTX007 is not able to neutralize LPS. Exemplary results are presented in Table 4. |
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