The present invention is inter alia concerned with (i) a combination of a CBP/p300 bromodomain inhibitor and a KRAS inhibitor for use in the treatment of a patient suffering from cancer, wherein the cancer exhibits an oncogenic alteration in the KRAS; (ii) a kit comprising (a) a pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and (b) a pharmaceutical dosage form comprising a KRAS inhibitor, and (iii) a pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and a a KRAS inhibitor.

The present invention is inter alia concerned with (i) a combination of a CBP/p300 bromodomain inhibitor and a KRAS inhibitor for use in the treatment of a patient suffering from cancer, wherein the cancer exhibits an oncogenic alteration in the KRAS; (ii) a kit comprising (a) a pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and (b) a pharmaceutical dosage form comprising a KRAS inhibitor, and (iii) a pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and a a KRAS inhibitor.

Provided herein are optionally substituted benzoimidazol-1,2-yl amides, pharmaceutical compositions comprising a therapeutically effective amount of such compounds and a pharmaceutically acceptable excipient, and methods of treating Kv7 associated diseases, such as, epilepsy, amyotrophic lateral sclerosis, various types of pain, hyperexcitability, a dyskinesia, dystonia, mania and tinnitus with such compounds and pharmaceutical compositions.

Provided herein are optionally substituted benzoimidazol-1,2-yl amides, pharmaceutical compositions comprising a therapeutically effective amount of such compounds and a pharmaceutically acceptable excipient, and methods of treating Kv7 associated diseases, such as, epilepsy, amyotrophic lateral sclerosis, various types of pain, hyperexcitability, a dyskinesia, dystonia, mania and tinnitus with such compounds and pharmaceutical compositions.

The present application is directed to a method of inhibiting proliferation of chromosome instable cancer cells. This method involves administering, to a population of cancer cells comprising chromosome instable cancer cells, an inhibitor of Kinesin Family Member 18A (KIF18A) at a dosage effective to inhibit proliferation of said chromosome instable cancer cells. The inhibitors of KIF18A may also be used in a method treating cancer in a subject. This method involves selecting a subject having cancer, where the cancer is characterized by chromosomal instability, and administering to the subject an inhibitor of KIF18A at a dosage effective to treat the cancer in the subject. Also disclosed is a combination therapeutic including an inhibitor of Kinesin Family Member 18A (KIF18A) and agent that promotes microtubule turnover or a cyclin-dependent kinase (CDK) inhibitor.

The present application is directed to a method of inhibiting proliferation of chromosome instable cancer cells. This method involves administering, to a population of cancer cells comprising chromosome instable cancer cells, an inhibitor of Kinesin Family Member 18A (KIF18A) at a dosage effective to inhibit proliferation of said chromosome instable cancer cells. The inhibitors of KIF18A may also be used in a method treating cancer in a subject. This method involves selecting a subject having cancer, where the cancer is characterized by chromosomal instability, and administering to the subject an inhibitor of KIF18A at a dosage effective to treat the cancer in the subject. Also disclosed is a combination therapeutic including an inhibitor of Kinesin Family Member 18A (KIF18A) and agent that promotes microtubule turnover or a cyclin-dependent kinase (CDK) inhibitor.

The present application is directed to a method of inhibiting proliferation of chromosome instable cancer cells. This method involves administering, to a population of cancer cells comprising chromosome instable cancer cells, an inhibitor of Kinesin Family Member 18A (KIF18A) at a dosage effective to inhibit proliferation of said chromosome instable cancer cells. The inhibitors of KIF18A may also be used in a method treating cancer in a subject. This method involves selecting a subject having cancer, where the cancer is characterized by chromosomal instability, and administering to the subject an inhibitor of KIF18A at a dosage effective to treat the cancer in the subject. Also disclosed is a combination therapeutic including an inhibitor of Kinesin Family Member 18A (KIF18A) and agent that promotes microtubule turnover or a cyclin-dependent kinase (CDK) inhibitor.

Endometriosis is a chronic inflammatory systemic sex hormone-dependent gynecological disease, characterized by the presence and growth of endometrial tissue (glands and stroma) outside the uterine cavity, predominantly, but not exclusively, in the pelvic compartment. Here, the inventors show that the use of Neuropilin/VEGF binding inhibitors, so called, Neuropilin antagonist (NRPa), bring new perspective to treat and cure endometriosis in women suffering thereof. NRPa alone is efficient to inhibit primary endometrial cell proliferation and apoptosis/necrosis program cell death of targeted cells. The effective NRPa concentration needed is very low (NRPa-48 IC.sub.50=10.sup.−7M) and is dependent of the NRPa structure. Moreover, the association of NRPa with progestogen drug increases the anti-proliferative effect. Therefore, the present invention relates to the use of neuropilin antagonists for the treatment of endometriosis.

Endometriosis is a chronic inflammatory systemic sex hormone-dependent gynecological disease, characterized by the presence and growth of endometrial tissue (glands and stroma) outside the uterine cavity, predominantly, but not exclusively, in the pelvic compartment. Here, the inventors show that the use of Neuropilin/VEGF binding inhibitors, so called, Neuropilin antagonist (NRPa), bring new perspective to treat and cure endometriosis in women suffering thereof. NRPa alone is efficient to inhibit primary endometrial cell proliferation and apoptosis/necrosis program cell death of targeted cells. The effective NRPa concentration needed is very low (NRPa-48 IC.sub.50=10.sup.−7M) and is dependent of the NRPa structure. Moreover, the association of NRPa with progestogen drug increases the anti-proliferative effect. Therefore, the present invention relates to the use of neuropilin antagonists for the treatment of endometriosis.

Endometriosis is a chronic inflammatory systemic sex hormone-dependent gynecological disease, characterized by the presence and growth of endometrial tissue (glands and stroma) outside the uterine cavity, predominantly, but not exclusively, in the pelvic compartment. Here, the inventors show that the use of Neuropilin/VEGF binding inhibitors, so called, Neuropilin antagonist (NRPa), bring new perspective to treat and cure endometriosis in women suffering thereof. NRPa alone is efficient to inhibit primary endometrial cell proliferation and apoptosis/necrosis program cell death of targeted cells. The effective NRPa concentration needed is very low (NRPa-48 IC.sub.50=10.sup.−7M) and is dependent of the NRPa structure. Moreover, the association of NRPa with progestogen drug increases the anti-proliferative effect. Therefore, the present invention relates to the use of neuropilin antagonists for the treatment of endometriosis.