The present invention relates to seco (opened ring) macrolide compounds, to the process for preparation thereof, to the use of said seco macrolide compounds as intermediates for preparation of macrolide based macrocycles, to macrolide based macrocycles obtained from said seco macrolide compounds, to the process for preparation of macrolide based macrocycles, to the pharmaceutical compositions comprising macrolide based macrocycles, and to the use of macrolide based macrocycles as therapeutic agents.

Disclosed are compositions of matter, therapeutics, and protocols useful for reduction and/or reversion of pulmonary fibrosis. In one specific embodiment lithium chloride is administered together with a regenerative cell in a patient suffering from, or at risk of pulmonary fibrosis. In one embodiment said lithium chloride is administered as an adjuvant to a regenerative therapy, wherein said regenerative therapy is a gene therapy, a protein therapy, a cell therapy, or a tissue transplant. In one embodiment lithium chloride, or a salt thereof is utilized alone, or with a regenerative means, to evoke preservation and/or elongation of telomere length in pulmonary tissue.

Disclosed are compositions of matter, therapeutics, and protocols useful for reduction and/or reversion of pulmonary fibrosis. In one specific embodiment lithium chloride is administered together with a regenerative cell in a patient suffering from, or at risk of pulmonary fibrosis. In one embodiment said lithium chloride is administered as an adjuvant to a regenerative therapy, wherein said regenerative therapy is a gene therapy, a protein therapy, a cell therapy, or a tissue transplant. In one embodiment lithium chloride, or a salt thereof is utilized alone, or with a regenerative means, to evoke preservation and/or elongation of telomere length in pulmonary tissue.

Amino-pyrazinecarboxamide compounds, conjugates, and pharmaceutical compositions for use in the treatment of disease, such as cancer, are disclosed herein. The disclosed compounds are useful, among other things, in the treating of cancer and fibrosis and modulating TGFβR2. Additionally, compounds incorporated into a conjugate with an antibody construct are described herein.

Provided herein are methods involving a compound of the following structural formula: (I) or a pharmaceutically acceptable salt thereof, wherein values for the variables are as described herein. For example, methods for inhibiting replication of a virus, treating a viral infection, inhibiting heat shock protein 90 and treating a heat shock protein 90-mediated disease or condition using a compound of Structural Formula I are provided.

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Provided herein are methods involving a compound of the following structural formula: (I) or a pharmaceutically acceptable salt thereof, wherein values for the variables are as described herein. For example, methods for inhibiting replication of a virus, treating a viral infection, inhibiting heat shock protein 90 and treating a heat shock protein 90-mediated disease or condition using a compound of Structural Formula I are provided.

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The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading is capability retained. The process is scalable and the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and predictable drug retention when the liposome encapsulated drug is administered in patients.

The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading is capability retained. The process is scalable and the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and predictable drug retention when the liposome encapsulated drug is administered in patients.

Compositions and articles comprising diamond particles, such as nanodiamond based pharmaceutical compositions, are generally provided. In some embodiments, the articles and methods comprising (nano)diamond particles may be useful for monitoring and/or treating a disease (e.g., in a subject).

Methods of treating a valvular heart disease are provided. Methods for treating valvular heard disease include administering to a subject a therapeutically effective amount of at least one hedgehog pathway inhibitor. Also provided are methods for reducing fibrosis in a subject, which comprise administering to the subject a therapeutically effective amount of at least one hedgehog pathway inhibitor.