Pfizer Presents Promising Data from Next Generation ALK/ROS1 Inhibitor in Advanced Non-Small Cell Lung Cancer

Pfizer Inc.    announced encouraging new data from a Phase 1/2 study of lorlatinib, the proposed generic name for PF-06463922, Pfizer’s investigational, next-generation ALK/ROS1 tyrosine kinase inhibitor. The study showed clinical response in patients with ALK-positive or ROS1-positive advanced non-small cell lung cancer (NSCLC), including patients with brain metastases. These data were presented today in an oral presentation at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

lorlatinib

The results presented are from the dose escalation component of an ongoing Phase 1 study of patients with ALK-positive or ROS1-positive NSCLC, with or without brain metastases, who were treatment-naïve or had disease progression after at least one prior tyrosine kinase inhibitor (TKI). Among patients with ALK-positive metastatic NSCLC, the overall response rate (ORR) with lorlatinib was 46 percent, with three patients achieving complete responses and 16 patients achieving a partial response (95% CI: 31-63). The median progression free survival (PFS) was 11.4 months (95% CI: 3.4 – 16.6). The majority of patients had received two or more prior ALK TKIs. Additionally, lorlatinib showed the ability to decrease the size of brain metastases in patients with ALK-positive or ROS1-positive metastatic NSCLC.

“Many patients with ALK-positive or ROS1-positive metastatic NSCLC will progress beyond initial therapy and potentially develop brain metastases,” said Benjamin Solomon, MBBS, Associate Professor, Peter MacCallum Cancer Centre, Australia. “These early data suggest lorlatinib may be effective in a broad range of patients, including those who are heavily pre-treated or develop brain metastases. We are encouraged by these results and look forward to further investigating the full effects of lorlatinib in ALK-positive and ROS1-positive NSCLC.”

“We are excited by these data and the potential of lorlatinib to overcome resistance to ALK inhibitors, which remains a significant challenge for patients with ALK-positive NSCLC,” said Mace Rothenberg, MD, senior vice president, head of development, Pfizer Oncology. “Pfizer pioneered precision medicine in ALK-positive advanced NSCLC through the introduction of XALKORI® (crizotinib), which is widely recognized as a first-line standard of care for these patients, and we are committed to developing next-generation treatments that meet these patients’ evolving needs.”

In the phase 1 portion of the study, patients received lorlatinib on a continuous basis, once or twice daily. The primary objective was to identify the maximum tolerated dose and recommended Phase 2 dose. Patients were treated across 10 dose levels (10–200 mg). The recommended Phase 2 dose was 100 mg once daily. Other objectives included safety and efficacy by RECIST v1.1 including intracranial activity. Of 54 patients treated as of January 15, 2016, 41 were ALK-positive, 12 were ROS1-positive and one was unconfirmed. The majority of patients were previously treated with a TKI, including 20 with one prior TKI and 27 with more than one TKI. Additionally, 39 patients had brain metastases at baseline.

The most common treatment-related adverse events (AEs) were hypercholesterolemia (69%) and peripheral edema (37%). Hypercholesterolemia was the most common (11%) grade 3 or higher treatment-related AE and the most frequent reason for dose delay or reduction. No patients discontinued due to treatment-related AEs. At the recommended Phase 2 dose, 4 out of 17 patients (24%) experienced a treatment-related AE of any grade that led to a dose delay or hold.

The ongoing Phase 2 study is expected to enroll a total of 240 patients across six cohorts (five for ALK-positive and one for ROS1-positive patients with NSCLC), with enrollment defined by degree and type of prior treatment.

About Lorlatinib

Lorlatinib, the proposed generic name for PF-06463922, is an investigational next-generation ALK/ROS1 tyrosine kinase inhibitor that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of both ALK and ROS1. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. A Phase 1/2 clinical trial of lorlatinib in patients with ALK-positive or ROS1-positive advanced NSCLC is currently ongoing. Lorlatinib has not yet been approved by any regulatory agency.

Pfizer Presents Promising Data from Next Generation ALK/ROS1 Inhibitor in Advanced Non-Small Cell Lung Cancer  

This Diabetes Drug Saves Lives. You Can Thank The FDA

Researchers are announcing that Victoza, a diabetes drug sold by Danish drug giant Novo Nordisk , prevents heart attacks, strokes and cardiovascular deaths.

 liraglutide-Victoza

It is only the second diabetes drug ever to do so. The first, Jardiance, a pill sold by Eli Lilly LLY -0.91% and Boehringer Ingelheim , presented its positive results just last year. Researchers say that the new results could change the way that doctors treat diabetes, shifting the treatments doctors reach for after metformin, the tried-and-true first-line drug, which is generic. “There’s a building momentum that maybe we do need to rethink the way diabetes is cared for in America,” says John Buse, the University of North Carolina, Chapel Hill researcher who led the study, which was funded by Novo Nordisk.

And doctors and Novo Nordisk itself give credit to the new diabetes data to a surprising source: Tougher regulations for diabetes drugs from the Food and Drug Administration, which many in industry had previously decried, saying it was keeping new drugs from the market and hurting patients. “I can almost guarantee you that these trials would not have been done if it had not been for the FDA regulations,” says Buse, who has been a consultant to many companies for years. “Before the guidance I was constantly pushing on companies to do these trials.”

That fact–that companies and patients are likely to benefit from the FDA’s toughness–goes against one of the common narratives in the drug industry and among the FDA’s critics: that high regulations slow patients’ access. In some cases, it’s clear, they also create a bar for industry to leap over, and deliver billions of dollars in spoils to companies that actually manage to help patients, not just blood test results.

The Victoza result is exactly the kind of marketing claim that makes a drug company salivate: Novo Nordisk can now tell patients and their insurers that the alternative to its drug is an earlier death.

In the study, presented this evening at the annual meeting of the American Diabetes Association and published in the New England Journal of Medicine, 9,340 patients were randomly assigned to receive either Victoza or placebo for a median of 3.8 years. For those on Victoza, 13% had a heart attack, stroke or death, compared to 14.9% on placebo, a 13% decrease in risk. Reductions in cardiovascular death (22%) and death from any cause (15%) were also statistically significant. A supposed side effect of the drug, pancreatitis, did not show up at all, and patients on Victoza lost 2.3 kilograms (about 5 pounds) more than those on placebo.

Diet Drugs: Which Ones Work?

Any of the prescription weight-loss drugs on the market can help obese people shed pounds, although some seem more effective than others, a new study finds.

Currently, five drugs are approved in the United States for managing obesity. But little has been known about how they stack up against one another, said Dr. Siddharth Singh, the lead researcher on the new study.

The findings  based on more than 29,000 people in total show all five drugs can work. But people on certain drugs tended to be more successful, at least over one year.

Specifically, people using Qsymia (phentermine-topiramate) or Victoza (liraglutide) had the highest odds of shedding at least 5 percent of their initial weight. Those taking Xenical (orlistat) had the lowest odds.

phentermine liraglutide

 orlistat  lorcaserin

 Bupropion/naltrexone 

However, there is no single drug that's "best" for everyone, stressed Singh, an assistant clinical professor at the University of California, San Diego.

He cautioned that his team's numbers are just averages across study groups. Plus, he said, the side effects of each medication vary, and that is an important factor in treatment decisions.

"Obesity treatment always needs to be personalized," Singh said.

Nikhil Dhurandhar, a spokesman for the Obesity Society, agreed that people respond differently to any given weight-loss drug.

"In general, if you give drug 'X,' there will be a wide variation in patients' responses," said Dhurandhar, who is also a professor of nutritional sciences at Texas Tech University in Lubbock. He wasn't involved in the study.

Some people will have "zero" weight loss   or even gain weight -- while others will see the pounds drop off, Dhurandhar said.

He also stressed that there is no such thing as a magic weight-loss pill.

"These drugs can help you eat less through effects on appetite," Dhurandhar explained. "But you have to change your diet and get regular exercise."

"Medications are supplements, not substitutes, to your efforts," he said.

For the study, Singh's team analyzed findings from 28 clinical trials testing the five approved drugs for obesity: Qsymia, Victoza and Xenical, along with Belviq (lorcaserin) and Contrave (naltrexone-bupropion).

On average, the researchers found, each drug worked better than a placebo in helping obese adults lose weight over a year. But certain medications seemed more effective than others.

People on Qsymia typically lost the most weight -- almost 20 pounds more, versus study patients given placebo pills. They were also nine times more likely to drop at least 5 percent of their initial weight, the researchers found.

People taking Xenical or Belviq tended to shed the fewest pounds -- 6 to 7 pounds more than placebo users. Contrave and Victoza patients typically lost 11 to 12 pounds more, compared with placebo.

But not everyone benefited. In studies of all of the drugs, Singh noted, a significant number of people dropped out because of side effects.

And those dropouts were more common with certain medications, the study found. People taking Contrave or Victoza were almost three times more likely to quit a trial over side effects, compared with placebo users. According to Victoza's maker, the drug can cause inflammation of the pancreas or kidney problems.

Just as people vary in their weight-loss success with any given drug, their risks of side effects will differ, too, Singh said.

He pointed to Contrave as an example. Because it contains the antidepressant bupropion, it carries a boxed warning about the potential risk of suicidal thoughts. So it might not be the best choice for someone with psychiatric conditions that could make them more vulnerable, Singh said.

Victoza, meanwhile, is an injection drug prescribed for controlling high blood sugar in people with type 2 diabetes. So if a patient needs medication for diabetes as well as weight loss, Victoza might be a good option, Singh said.

Most of the medications have been approved only in the past few years, so one question is whether they maintain their effects over the long run, Singh said.

"We do need more long-term data," Dhurandhar agreed.

Still, he said, medications are an important option for managing obesity. And if one does not work, Dhurandhar added, he'd recommend trying another.

Mycobacterium in olive oil for cancer treatment

Since then, they have been looking for ways to improve the immunotherapeutic activity of M. brumae through the design of different emulsions which can increase the homogeneity and stability, and therefore the efficacy, of the mycobacteria solutions when introduced into the body.

Researchers found a way to reduce the clumps produced naturally when mycobacteria cells, which possess a high content of lipids in their walls, are introduced into the usual aqueous solutions used for intravesical instillation in bladder cancer patients. This clumping may interfere with the interaction of the mycobacteria-host cells and negatively influence their antitumor effects.

Of the emulsions tested, the one based on olive oil induce a prominent immune response in both in vitro and in vivo experiments. Olive oil preserves the viability of the mycobacteria and provided higher anti-clumping rates, and this indicates favourable conditions for reaching the bladder.

According to Esther Julián, "these results highlight the potential of the olive oil-based emulsion as a promising delivery vehicle for the mycobacterial treatment of bladder cancer."

The work, recently published in the journal Scientific Reports, from the publishers of Nature, was conducted by scientists from the Department of Genetics and Microbiology of the Faculty of Biosciences, the Department of Animal Medicine and Surgery of the Faculty of Veterinary Medicine, and the Microbiology Service of the UAB, together with the Bacterial Infections and Antimicrobian Therapies group at the IBEC, Barcelona.

Is Avocado Good for Diabetes?

  

The humble avocado, shunned for years during the fat-free diet craze of the 1990s, may have finally hit its stride. No longer just for guacamole, this nutritious fruit is popping up as a healthy addition to various diet plans.

But can people with diabetes eat this food? It turns out that avocados are not only safe for people with diabetes, but they may be downright beneficial. Research shows that avocados offer many ways to help people manage their diabetes and improve their overall well-being.

Diet and diabetes

A healthy diet is critical for people with diabetes. The foods that they eat each day can have a considerable impact on how they feel and how well their diabetes is controlled.

In general, people with diabetes should eat foods that help control blood sugar levels and that offer health benefits such lowering blood pressure and cholesterol. This is one of the best ways to keep diabetes under control, avoid complications, and lead the healthiest life possible.

Avocados are an excellent choice for people with diabetes because they offer all these benefits - and possibly more.

Blood sugar control is critical for people who have diabetes. A physician or dietitian may advise patients to choose foods that are lower in carbohydrates and sugar. They may also recommend foods that help control blood sugar spikes. An avocado meets both of these requirements.

According to the United States Department of Agriculture, an average medium avocado has around 17 grams of carbohydrates. For comparison, an apple has 25 grams of carbohydrates and a banana has 27.

A 1-ounce serving, or about one-fifth of an avocado, contains only 3 grams of carbohydrates and less than 1 gram of sugar.

With so few carbohydrates, people with diabetes likely won't need to worry about an avocado raising their blood sugar levels.

Pairing an avocado with other foods may help reduce blood sugar spikes too. Its fat and fiber content takes longer to digest and slows the absorption of other carbohydrates in the process.

How much avocado can people with diabetes eat?

Before people make any significant changes to their diet, they should talk with their physician or dietitian. One of the things to consider is total calorie intake.

A whole avocado contains 250-300 calories, but a 1-ounce serving has only 50. People who are watching their calories in order to maintain or lose weight can still add avocado to their diet. This can be done by switching a serving of avocado for something else with a similar amount of calories like cheese or mayonnaise.

The American Diabetes Association (ADA) say people should pay attention to the type of fat they're eating more than the amount.

Specifically, people should strictly limit the unhealthy fats. This includes saturated fats and trans fats, often found in fatty meats, fried foods, processed and restaurant foods.

The ADA encourage people with diabetes to consider adding avocado into their diets due to its healthy fats.

Avocados and heart health

Avocados have fat and are calorie-dense, but this is not a reason for people with diabetes to avoid them.

The fats in avocados are mostly monounsaturated fatty acids (MUFAs), which have been shown to raise "good" HDL cholesterol. MUFAs can also lower levels of "bad" LDL cholesterol and fats called triglycerides, and reduce blood pressure.

Having healthy cholesterol, triglyceride, and blood pressure levels can reduce the risk of heart disease and stroke, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

People with diabetes are twice as likely to have heart disease and stroke as someone without diabetes, according to the NIDDK. More importantly, heart disease and stroke are the leading causes of death among people with diabetes.

There may be an additional reason that MUFAs are a ticket to better health when living with diabetes. A study published in the Journal of the American College of Nutrition suggests that these fats may help control blood sugar and insulin levels.

The researchers found this was particularly the case when replacing some carbohydrates in the diet with MUFAs. So besides being naturally low in sugar and carbohydrates, an avocado's healthy fats can help lower blood sugar levels even more.

Fiber, blood sugar levels, and feeling full

A medium avocado has an impressive 10 grams of fiber. For reference, men should get 30-38 grams of fiber per day, and women need 21-25 grams, according to the Academy of Nutrition of Dietetics.

Fiber is an important part of a healthy diet because it improves digestive health and keeps the bowels regular. It's particularly helpful for people with diabetes because it helps improve blood sugar levels.

A study in the Journal of the American Board of Family Medicine suggests that fiber can lower fasting blood sugar levels and hemoglobin A1C levels in people with diabetes.

Soluble fiber, which is present in avocados, may also improve cholesterol levels, according to a study in the American Journal for Clinical Nutrition. This is another way this fruit may help reduce the risk of heart disease.

Avocados may also help people feel fuller for longer. This can help people control their calorie intake without feeling hungry. A study in the Nutrition Journal found that eating half of an avocado with lunch increased levels of feeling full up to 5 hours later.

Is Avocado Good for Diabetes?

Is Okra Good for Diabetes?

According to a handful of recent studies, okra may reduce symptoms of diabetes - a group of diseases that includes type 1 diabetes, type 2 diabetes, and gestational diabetes.

 

Diabetes claimed the lives of 75,578 Americans in 2013, according to the United States Centers for Disease Control and Prevention (CDC). In 2014,8.5 percent of adults worldwide had the condition, the World Health Organization (WHO) report. By 2030, diabetes may be the seventh leading cause of death.

A number of factors increase a person's risk of developing diabetes, including a family history of the disease. Lifestyle factors also play a role, so doctors routinely recommend diet changes and increased exercise to reduce blood sugar levels.

Okra may help reduce blood sugar levels in some people with diabetes. Research into the effects of this seedy vegetable is still in the early stages, but the results are promising.

Okra thrives in temperate climates, producing large hibiscus-like flowers that eventually give rise to green seed pods. It is a member of the mallow family, which includes a number of other popular plants, including hibiscus, cocoa, and cotton.

Scientifically known as Abelmoschus esculentus, okra may have been grown as long ago as 2000 BCE in Egypt.

Okra's flavor is mild, and the entire seed pod can be eaten. This vegetable-like fruit also has a long history in traditional medicine.

Kew Royal Botanic Gardens report that in Eastern traditional medicine, okra leaves and fruit were used as pain relievers, moisturizers, and to treat urinary disorders. In Congolese medicine, okra is used to encourage a safe delivery during childbirth.

Can okra help with symptoms of diabetes?

Diabetes can often be well-managed with increasing a hormone called insulin and other medical therapies. However, some people with diabetes wish to avoid regular insulin injections. Others experience blood sugar dips and other unpleasant side effects, and diabetes medications do not work for everyone.

The possibility that a readily available seed pod could help control diabetes is an exciting one. But there is no evidence yet that okra can cure diabetes. So far, the research on okra has only looked at its effects on animals. Human bodies are similar to animals, but not all research on animals has worked out in humans.

Increased absorption of sugar by muscles

A 2005 study published in Planta Medica investigated the effects of okra on rats with diabetes. A substance called myricetin is present in okra and some other foods, including red wine and tea.

Researchers isolated myricetin from okra, then administered it to the rat. The treatment increased absorption of sugar in the rats' muscles, lowering their blood sugar.

A 2012 Food Science and Human Wellness review points to a number of other laboratory and animal studies that have linked myricetin to lower blood sugar. The study argues that myricetin may also reduce other risk factors for diabetes.

Reduction in blood sugar spikes after eating

A 2011 study published in ISRN Pharmaceutics found a link between okra and decreased blood sugar spikes after eating.

Researchers fed rats liquid sugar as well as purified okra through a feeding tube. Rats who consumed the okra experienced a reduction in blood sugar spikes after feeding. The study's authors think this is because the okra blocked the absorption of sugar in the intestines.

The study also explored possible interactions between okra and metformin, a drug that can reduce blood sugar in type 2 diabetes. Okra appeared to also block absorption of metformin. This suggests that okra could reduce the effectiveness of metformin, and should therefore not be eaten at the same time as the drug.

Lower blood sugar levels

A 2011 study published in the Journal of Pharmacy and Bioallied Sciences points to a link between eating okra and lower blood sugar. The researchers allowed the blood sugar of rats with diabetes to stay level for 14 days. They then gave the rats powdered okra peel extracts and seeds dosages of up to 2,000 milligrams per kilogram of body weight.

There were no poisonous effects linked with these relatively high doses of okra. The rats that ate okra had reduced blood sugar levels after up to 28 days of eating okra. The study ended on day 28, so it is unclear if the effects on blood sugar levels would have lasted longer.

Considerations for using okra

Few studies have linked okra to negative side effects, but some negative side effects are possible:

• Okra may make the drug metformin less effective.
• Okra is high in substances known as oxalates. Oxalates may increase the risk of kidney stones in people vulnerable to kidney stones.
• Okra can contain bacteria, pesticides, and other dangerous substances if it is not thoroughly washed. People should never consume rotten okra, frozen okra that is past its expiration date, or okra that has not been thoroughly washed.
• People with an okra allergy should not consume okra. Those with an allergy to other plants in the mallow family, such as hibiscus or cotton, may also be allergic to okra.
• Even if okra proves to be ineffective in fighting diabetes, it remains a safe snack for people with diabetes. A single serving of 100 grams contains just 30 calories, but offers a number of nutritional benefits:
  • Okra contains no saturated fats or cholesterol
  • Okra is rich in fiber, containing 9 percent of the recommended daily value (RDV)
  • Okra contains 8 percent of the RDV of calcium, 43 percent of the RDV of manganese, 10 percent of the RDV of iron and copper, and 44 percent of the RDV of vitamin K
  Okra is rich in protective substances known as antioxidants, including myricetin. According to the National Center for Complementary and Integrative Health, antioxidants may reduce oxidative stress, a process that damages cells in the body. Oxidative stress plays a role in the development of diabetes, as well as diseases such as:
  • Parkinson's disease
  • Alzheimer's disease
  • Cataracts
  • Macular degeneration
  • Heart and blood vessel disease
  • Cancer
  In addition to its antioxidant benefits, okra may also reduce tiredness. A 2015 study published in Nutrients found that substances found in okra seeds known as polyphenols and flavonoids could reduce fatigue.

Broccoli sprout extract may protect against oral cancer recurrence

It is the first study demonstrating that the extract protects against oral cancer, with the results of human, animal and laboratory tests reported in the journalCancer Prevention Research. This research is funded through Pitt's Specialized Program of Research Excellence grant in head and neck cancer from the National Cancer Institute.

"With head and neck cancer, we often clear patients of cancer only to see it come back with deadly consequences a few years later," said lead author Julie Bauman, M.D., M.P.H., co-director of the UPMC Head and Neck Cancer Center of Excellence. "Unfortunately, previous efforts to develop a preventative drug to reduce this risk have been inefficient, intolerable in patients and expensive. That led us to 'green chemoprevention'--the cost-effective development of treatments based upon whole plants or their extracts."

Cruciferous vegetables, such as broccoli, cabbage and garden cress, have a high concentration of the naturally occurring molecular compound sulforaphane, which previously has been shown to protect people against environmental carcinogens.

Dr. Bauman and her colleagues treated human head and neck cancer cells in the laboratory with varying doses of sulforaphane and a control, and compared them to normal, healthy cells that line the throat and mouth. The sulforaphane induced both types of cells to increase their levels of a protein that turns on genes that promote detoxification of carcinogens, like those found in cigarettes, and protect cells from cancer.

In a small preclinical trial, 10 healthy volunteers drank or swished fruit juice mixed with broccoli sprout extract for several days. The volunteers had no significant problems tolerating the extract and the lining of their mouths showed that the same protective genetic pathway activated in the laboratory cell tests was activated in their mouths, meaning that the sulforaphane was absorbed and directed to at-risk tissue.

Dr. Bauman also collaborated with senior author Daniel E. Johnson, Ph.D., professor of medicine at Pitt and a senior scientist in the UPCI Head and Neck Cancer Program, to see how the extract performed in mice predisposed to head and neck cancer. The mice who received the sulforaphane developed far fewer tumors than their counterparts who did not receive the extract.

The results of the mouse, human and lab studies have been so successful that Dr. Bauman has started a larger clinical trial in volunteers previously cured of head and neck cancer. These participants are taking capsules containing broccoli seed powder, which is more convenient to take regularly than the extract mixed with juice.

"Head and neck cancers account for approximately 3 percent of all cancers in the U.S., but that burden is far greater in many developing countries," said Dr. Bauman. "A preventative drug created from whole plants or their extracts may ease the costs of production and distribution, and ultimately have a huge positive impact on mortality and quality of life in people around the world."

Ref : http://cancerpreventionresearch.aacrjournals.org/content/early/2016/04/30/1940-6207.CAPR-15-0290

Broccoli sprout extract may protect against oral cancer recurrence  

Scientists streamline total synthesis of uncialamycin drug

A team led by Rice University scientists has improved the production of a potent anti-tumor antibiotic known as uncialamycin.

The Rice lab of synthetic chemist K.C. Nicolaou announced this month it had streamlined the total synthesis of uncialamycin to make it simpler to create novel variations of the molecule. Such variations could allow the substance, which is too toxic in its original form, to be made into useful drugs to fight cancer.

The new work by Nicolaou and colleagues appears in the Journal of the American Chemical Society.

Nicolaou's lab specializes in the synthesis of molecules found in nature with medicinal properties, but in amounts too small for testing or clinical use. The new process is scalable for bulk production, he said.

Uncialamycin is an enediyne, compounds defined by the presence of nine- and 10-member atomic rings in their structures. Two other enediynes, neocarzinostatin and calicheamicin, are or have been used as chemotherapy agents to treat leukemia and cancers of the liver and the brain.

"The 10-member ring is like the warhead of the molecule," Nicolaou said. "The ring undergoes the Bergman reaction, producing radicals that cut both strands of the DNA, rendering it difficult to repair by the cell. It's a Trojan horse that gets inside the cell and causes havoc."

The payoff has been a long time coming for Nicolaou and his colleagues who began investigating uncialamycin after it was isolated from a strain of streptomycete related to Streptomyces cyanogenus, a marine bacterium, in 2005. The lab reported the total synthesis of the molecule in 2007 and followed up in 2008 with a report on new synthetic versions and demonstration of its DNA-cleaving, antibiotic and cytotoxic capabilities.

He said the newly developed synthetic strategies and methods make it possible to synthesize a series of designed analogs of the molecule for biological evaluation. As part of the new study, the lab synthesized not only pure synthetic uncialamycin but also 13 variants of the molecule, with handles for attachment to cancer-cell-associated antibodies and other drug-delivery systems.

These were tested for their potency against lung, gastric, ovarian and multidrug-resistant cancer cell lines. Three of the variants showed "remarkably high potency against the tested cell lines," the researchers reported.

Nicolaou said the analogs proved stable enough to be used as payloads in antibody drug conjugates that combine a delivery system - an antibody capable of recognizing and targeting cancer cells - with the anti-cancer drug through a chemical linker that joins the two until they reach the target.

Ref : http://pubs.acs.org/doi/abs/10.1021/jacs.6b04339