Tel Aviv University

Ramot University Authority for Applied Research and Industrial Development Limited

Kadmon Corporation, LLC

Yoel Kloog

Michael Jay Brownstein

Liat Goldberg

Roni Haklai

Gad Keren

Joab Chapman

Victor J Bauer

Jonathan Elsner

Amir Kraitzer

Gilad Ben-Baruch

Adi Zundelevich

Jakob George

Ariella Paz

Shimon Reif

Rafael Bruck

Dimitrius Karussis

Michael Brownstein

Disclosed are alkoxyalkyl S-prenylthiosalicylates and pharmaceutical compositions containing the same and a pharmaceutically acceptable carrier. Methods for treating a human afflicted with cancer, including solid tumors, or a hematological malignancy by administering to the human in need thereof an effective amount of an alkoxyalkyl S-prenylthiosalicylate are also disclosed.

Alkoxyalkyl S-prenylthiosalicylates for treatment of cancer

Methods of treating cancer by administering effective amounts of a Ras antagonist comprising FTS, or analogs thereof, or a pharmaceutically acceptable salt, and 2-deoxyglucose (2DG) to a patient are disclosed. Pharmaceutical compositions useful in treating cancer containing a Ras antagonist comprising FTS, or analogs thereof, or a pharmaceutically acceptable salt, and 2DG are also disclosed.

Cancer treatment using FTS and 2-deoxyglucose

Disclosed are methods of treating ovarian cancer by administering an effective amount of FTS (farnesylthiosalicylic acid), or various analogs thereof, or a pharmaceutically acceptable salt, optionally with, a platinum-based chemotherapy drug to a human diagnosed with ovarian cancer.

Treatment of ovarian cancer

Disclosed are methods of treating lung cancer by administering to a human in need thereof effective amounts of FTS, or various analogs thereof, or a pharmaceutically acceptable salt thereof, optionally, in combination with a chemotherapeutic agent. Chemotherapeutic agents, and combinations thereof, for use with FTS, its analogs, or its salts are also disclosed.

Treatment of lung cancer

Novel farnesyl derivatives which are inhibitors of the prenylated protein methyltransferase enzyme, and useful as anti-cancer drugs, have the following formula:wherein

Farnesyl derivatives and pharmaceutical compositions containing them

Disclosed are methods for inhibiting Ras activity such as cell proliferation associated with vascular injury such as post-angioplasty restenosis and atherosclerosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof.

Treatment of post-angioplasty restenosis and atherosclerosis with Ras antagonists

A drug screening assay for identifying compounds for their potential effects on the long chain fatty acid dependant intracellular membrane anchorage sites of lipoproteins. Membranes-anchoring-target are incubated in the presence of the compound to be tested and the proportion of the target that is released by the compound is detected and quantitated. The benchmark for this assay are the prenylated proteins such as the farnesylated and palmitoylated oncogenic ras trigger proteins which are displaced from their anchorage at the intracellular plasma membrane by derivatives of Farnesyl Thiosalicylic Acid (FTS). The assay is adaptable to flexibly assay a large variety of anchored targets using a wide range of labeling and detection techniques in test wells, tissue culture, and in animals as injected cells or transgenic, thereby directly addressing a wide range of pharmacologically relevant needs.

Drug screen targeting lipoprotein-membrane anchorage

Disclosed is a method for inhibiting Ras-induced or mediated proliferation of cells associated with a non-malignant disease, disorder or pathological condition. The method entails administering to a patient a Ras antagonist in an amount effective to inhibit the proliferation. The invention is particularly applicable to diseases characterized by a proliferation of T-cells such as autoimmune disease, e.g., type 1 diabetes, lupus and multiple sclerosis, and pathological states such as graft rejection induced by the presentation of a foreign antigen such as a graft in response to a disease condition (e.g., kidney failure). Other non-malignant diseases characterized by proliferations of cells include cirrhosis of the liver and restenosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof.

Non-malignant disease treatment with Ras antagonists

Novel farnesyl derivatives which are inhibitors of the prenylated protein thyltransferase enzyme, and useful as anti-cancer drugs, have the following formula: ##STR1## wherein R.sup.1 represents farnesyl, geranyl or geranyl-geranyl;

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Herzliya, Israel

Yoel Kloog