Disclosed herein are small molecule SOS1 allosteric site inhibitors, pharmaceutical compositions, and methods of use thereof.

The present invention relates to a kit-of-parts comprising at least one mitochondrial uncoupler and at least one cationic amphiphilic drug and its use in medicine. The invention further relates to a pharmaceutical composition comprising at least one mitochondrial uncoupler and at least one cationic amphiphilic drug for use in medicine. Moreover, the invention is directed to the kit-of-parts and the pharmaceutical composition for use in the treatment of cancer, in particular glioma, pancreatic cancer, small cell lung cancer, metastatic prostate cancer, liver cancer and triple-negative breast cancer.

The present invention relates to a kit-of-parts comprising at least one mitochondrial uncoupler and at least one cationic amphiphilic drug and its use in medicine. The invention further relates to a pharmaceutical composition comprising at least one mitochondrial uncoupler and at least one cationic amphiphilic drug for use in medicine. Moreover, the invention is directed to the kit-of-parts and the pharmaceutical composition for use in the treatment of cancer, in particular glioma, pancreatic cancer, small cell lung cancer, metastatic prostate cancer, liver cancer and triple-negative breast cancer.

In one aspect, use of compounds as active agents to treat a hearing impairment and to prevent a hearing impairment, and methods of treating and/or preventing hearing impairments or disorders using the compositions are disclosed. Momelotinib and Fedratinib exhibit excellent protection against antibiotic-induced hearing loss in zebrafish and mice when administered prophylactically. In one aspect, Momelotinib or Fedratinib can be used as a therapy for the treatment and/or prevention of hearing loss. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

In one aspect, use of compounds as active agents to treat a hearing impairment and to prevent a hearing impairment, and methods of treating and/or preventing hearing impairments or disorders using the compositions are disclosed. Momelotinib and Fedratinib exhibit excellent protection against antibiotic-induced hearing loss in zebrafish and mice when administered prophylactically. In one aspect, Momelotinib or Fedratinib can be used as a therapy for the treatment and/or prevention of hearing loss. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The present invention generally relates to a pharmaceutical formulation that substantially increases the bioavailability of niclosamide or a pharmaceutically acceptable salt thereof for a variety of routes of delivery for therapeutic purposes. The newly enhanced formulation also substantially expands the potential therapeutic applications of niclosamide. Pharmaceutical compositions and methods of uses thereof are within the scope of this disclosure.

##STR00001##

The present invention generally relates to a pharmaceutical formulation that substantially increases the bioavailability of niclosamide or a pharmaceutically acceptable salt thereof for a variety of routes of delivery for therapeutic purposes. The newly enhanced formulation also substantially expands the potential therapeutic applications of niclosamide. Pharmaceutical compositions and methods of uses thereof are within the scope of this disclosure.

##STR00001##

Acquired hearing loss due to chemotherapy or noise exposure is a major health problem, and Cisplatin chemotherapy often causes permanent hearing loss in cancer patients. However, there are no FDA-approved drugs for the treatment or prevention of Cisplatin- or noise-induced hearing loss. In one aspect, use of Niclosamide, Ingenol, and Elesclomol as an active agent to treat a hearing impairment and to prevent a hearing impairment, and methods of treating and/or preventing hearing impairments or disorders using the compositions are disclosed. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Acquired hearing loss due to chemotherapy or noise exposure is a major health problem, and Cisplatin chemotherapy often causes permanent hearing loss in cancer patients. However, there are no FDA-approved drugs for the treatment or prevention of Cisplatin- or noise-induced hearing loss. In one aspect, use of Niclosamide, Ingenol, and Elesclomol as an active agent to treat a hearing impairment and to prevent a hearing impairment, and methods of treating and/or preventing hearing impairments or disorders using the compositions are disclosed. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Acquired hearing loss due to chemotherapy or noise exposure is a major health problem, and Cisplatin chemotherapy often causes permanent hearing loss in cancer patients. However, there are no FDA-approved drugs for the treatment or prevention of Cisplatin- or noise-induced hearing loss. In one aspect, use of Niclosamide, Ingenol, and Elesclomol as an active agent to treat a hearing impairment and to prevent a hearing impairment, and methods of treating and/or preventing hearing impairments or disorders using the compositions are disclosed. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.