Novel drug puts cancer cells under extreme metabolic stress

Data-driven models, such as Quantitative Structure Activity Relationships (QSAR), are incredibly attractive because they offer rapid methods for predicting molecular properties, including those that are difficult to access through fundamental chemical and physical theory. For new molecules, in related regions of chemical space to the training data, they can often be very accurate. The challenge is that they typically do not generalize across large diverse chemical and biological spaces. Therefore real care is needed when applying them to novel chemistry or biology. Some attempts to build more widely applicable QSAR models have been made in recent years, but most models in use today are still built for specific chemistries and properties owing to the scale and complexity of chemical space. When I started this work, especially for solubility predictions, the datasets were modest by today’s standards, often hundreds to a few thousand molecules. One of the first things that teaches you is to explore the data carefully, assess its quality and quantity, and only then move forward with modeling. The aim is to capture genuine relationships between numerical molecular descriptions and important target endpoints, but those relationships may be only locally generalizable. I also think the phrase “simple descriptors” is interesting. Some are simple, such as atom counts or bond counts, but others rely on detailed parameterization, group contributions, and graph-theoretical techniques. We still see these descriptors used today, sometimes alongside embeddings from graph neural networks or language models. The main lesson for me is that there is no single workflow. Each dataset, model, and end-use case needs careful thought.

The bulk of vitamins and supplements containing fish oil, biotin, and vitamins A, C, and E can potentially promote nail and hair growth. You can find dietary supplements with higher concentrations of vitamins and minerals that aid skin, hair, and nail health. Fish oil supplements make nails and hair shiny. Fish oil also serves as an agent that can decrease signs of aging. If sun exposure damages the skin, the omega-3 fatty acids in fish oil can help. Biotin, also known as B7, increases hair density and strengthens it. It is found naturally in bananas, eggs, and milk. Vitamins are vital for skin health as well. Vitamin A reduces acne flairs and helps with changes due to aging like wrinkling. A vitamin A deficiency may increase the risk of acne because it becomes difficult for dead skin to slough off hair follicles, blocking pores. Vitamin B lowers the risk of precancerous growths and nonmelanoma skin cancer. Vitamin C is an antioxidant. It leads the fight against free radicals to help stimulate collagen and brighten skin. It also helps to prevent the formation of unneeded melanin that causes uneven skin pigmentation.

I think we're only just scratching the surface at the moment. I think over the next couple of years, we'll start to see some major strides. Obviously, showing the effects on target identification takes some time with new molecules but, certainly, the repositioning effects should be seen in a few years. I think there is great promise in terms of being able to really tap into a much broader chemical space, so we can have a much wider and more varied chemical palette to be able to pick the best molecules for drug discovery from. Also, accelerating the ways in which we can look at the data and glean much more information from it can help us both in terms of patient selection for clinical trials and in terms of being able to pick up signals of efficacy and safety much earlier.

Carb cycling is an attempt to fine-tune your carbohydrate consumption to alter many aspects of your metabolism. Your plan will include the same protein intake each day but vary carbohydrates according to your activity. Your carb cycling plan may have three low or zero carb days, two moderate carb days, and two high carb days. Meeting your calorie requirements will require including more fats on low-carb days. Carb cycling needs much more planning than a usual calorie-controlled diet. One way is to match your carb cycling to your physical activity. If you go to the gym thrice a week, you could have carbs on those days. The carbs provide energy for your workout, prevent fatigue, and avoid the muscle loss sometimes seen with dieting. The days when you eat little to no carbs force your body to generate energy from other sources, like proteins and fats. But the days when you eat more carbohydrates might reverse this change. You must only eat a high-carb diet on the days you have a heavy workout, which uses up the calories.

We are now testing the drug in patients with earlier-stage pancreatic cancer, prescribing it while their tumors are still operable and before their cancer spreads.