Ushio-Fukai, M. et al. Cholesterol depletion inhibits epidermal growth factor receptor transactivation by angiotensin II in vascular smooth muscle cells: role of cholesterol-rich microdomains and focal adhesions in angiotensin II signaling. J Biol Chem 276, 48269–75 (2001).

The femurs obtained from healthy rats were cleaned of adherent muscle and connective tissues. All the experiments were performed following the policy approved by the National Institutes of Health Intramural Animal Use and Care Committee (IACUC-2012-047). The bone marrow cells (BMSCs) were obtained by cutting the ends of the femur and flushing the marrow with 5 mL Dulbecco’s modified Eagle’s medium (DMEM) containing 5.5 mM glucose (GIBCO, Grand Island, NY, USA), and 10% fetal bovine serum (FBS) (GIBCO) using a syringe fitted with a 25-gauge needle. The cells were seeded in a 75 cm2 culture flask (Corning, Lowell, MA, USA) and cultured in a humidified atmosphere (95% air, 5% CO2) at 37°C in DMEM containing 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin (GIBCO). The cells were refreshed every 2 days and maintained in the primary culture for 5 to 6 days. When the cells reached confluence, they were trypsinized and placed on new culture plates. To obtain homogeneous populations of BMSCs, single-cell-derived colony cultures were obtained using the limiting dilution technique. Identification of the obtained BMSCs was done and the results are shown in Supplementary Fig. S3.

Starkus, J., Beck, A., Fleig, A. & Penner, R. Regulation of TRPM2 by extra- and intracellular calcium. J. Gen. Physiol. 130, 427–440 (2007).

Lu, Y., Hu, Y., Kong, X. & Wang, D. Selection of component drug in activating blood flow and removing blood stasis of Chinese herbal medicinal formula for dairy cow mastitis by hemorheological method. J Ethnopharmacol. 116, 313–317 (2008).

        Normally, the complement system is tightly regulated to restrict activation to the site of infection and avoid injury to host tissues, or "self" cell surfaces. Under conditions of excessive or uncontrolled activation, the complement system plays a key role in a range of debilitating autoimmune and inflammatory diseases. In these conditions, the complement system causes damage:

The requirements and length of time for approval vary in different jurisdictions and could involve additional studies of Aramchol beyond those we currently anticipate, including potentially post-approval studies. The time required to obtain approval in other countries might differ from that required to obtain FDA approval in the United States. The marketing approval process in other countries may include all of the risks detailed above regarding FDA approval as well as other risks. In particular, in many countries outside the United States, it is required that a product receive pricing and reimbursement approval before the product can be commercialized. This can result in substantial delays in such countries. In other countries, product approval depends on showing superiority to an approved therapy. This can result in significant expense to conduct complex clinical trials. Finally, we do not have any products approved for sale in any jurisdiction, including international markets, and we do not have experience in obtaining regulatory approval in international markets. If we fail to comply with regulatory requirements in international markets or to obtain and maintain required approvals or if regulatory approvals in international markets are delayed, our target market will be reduced and our ability to realize the full market potential of Aramchol and any future product candidates will be harmed.

        Accordingly, assuming we, or any future collaborators, receive marketing approval for one or more of our product candidates, we, and any future collaborators, and our and their contract manufacturers will continue to expend time, money and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance and quality control.

Liz is definitely a good speaker and I hope she will get the funding she needs. However, I don’t like too much idea of creating a clinic offshore without the proper trials.

This story hangs together until we consider aspirin.  Aspirin inhibits both COX1 and COX2, and yet the preponderance of studies appear to show aspirin is associated with reduced CV risk [ref, ref].  This suggests there is a piece of the metabolic puzzle that is still missing.  Aspirin has many mechanisms of action, some of them unique to aspirin.

        Our success depends in large part on our ability to obtain and maintain patent protection and trade secret protection in the U.S. and other countries with respect to our proprietary product candidates. If we do not adequately protect our intellectual property rights, competitors may be able to erode, negate or preempt any competitive advantage we may have, which could harm our business and ability to achieve profitability. To protect our proprietary position, we file patent applications in the U.S. and abroad related to our product candidates that are important to our business; we also license or purchase patents and/or patent applications filed by others. The patent application and approval process is expensive and time-consuming. We may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner.

Hi Mark, My analysis study, Used overweight/obese people with high level insulin resistance. Drug promotes PPARG which promotes creation new fat cells. My guess fat people have feedback loop inhibition PPARG so don’t make new fat cells just make bigger fat cells. Piog stimulates PPARG so make new fat cells and fat people able to redistribute so have more small young cells and less old big cells in visceral fat. Net effect is without weight loss fat people reduce insulin resistance. Also small fat cells may be ones make Adiponectin which agree good. My take, good for fat people. My treatment plan: loose 50 pounds. That is best way have insulin sensitivity. When want to loose 50 pounds want low level PPARG. Note this was study on fat people. You is not fat person. You have healthy amount SC adipose tissue and don’t need any more.

        Moreover, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in foreign intellectual property laws. Additionally, laws of some countries outside of the U.S. and Europe do not afford intellectual property protection to the same extent as the laws of the U.S. and Europe. Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legal systems of some countries, including India, China and other developing countries, do not favor the enforcement of patents and other intellectual property rights. This could make it difficult for us to stop the infringement of our patents or the misappropriation of our other intellectual property rights. For