Metal-based complexes with their unique chemical properties, including multiple oxidation states, radio-nuclear capabilities and various coordination geometries yield value as potential pharmaceuticals. Understanding the interactions between metals and biological systems will prove key for site-specific coordination of new metal-based lead compounds. This study merges the concepts of target coordination with fragment-based drug methodologies, supported by varying the anomalous scattering of rhenium along with infrared spectroscopy, and has identified rhenium metal sites bound covalently with two amino acid types within the model protein. A time-based series of lysozyme-rhenium-imidazole (HEWL-Re-Imi) crystals was analysed systematically over a span of 38 weeks. The main rhenium covalent coordination is observed at His15, Asp101 and Asp119. Weak (i.e. noncovalent) interactions are observed at other aspartic, asparagine, proline, tyrosine and tryptophan side chains. Detailed bond distance comparisons, including precision estimates, are reported, utilizing the diffraction precision index supplemented with small-molecule data from the Cambridge Structural Database. Key findings include changes in the protein structure induced at the rhenium metal binding site, not observed in similar metal-free structures. The binding sites are typically found along the solvent-channel-accessible protein surface. The three primary covalent metal binding sites are consistent throughout the time series, whereas binding to neighbouring amino acid residues changes through the time series. Co-crystallization was used, consistently yielding crystals four days after setup. After crystal formation, soaking of the compound into the crystal over 38 weeks is continued and explains these structural adjustments. It is the covalent bond stability at the three sites, their proximity to the solvent channel and the movement of residues to accommodate the metal that are important, and may prove useful for future radiopharmaceutical development including target modification.

Structure-based drug design is highly dependent on the availability of structures of the protein of interest in complex with lead compounds. Ideally, this information can be used to guide the chemical optimization of a compound into a pharmaceutical drug candidate. A limitation of the main structural method used today – conventional X-ray crystallography – is that it only provides structural information about the protein complex in its frozen state. Serial crystallography is a relatively new approach that offers the possibility to study protein structures at room temperature (RT). Here, we explore the use of serial crystallography to determine the structures of the pharmaceutical target, soluble epoxide hydro­lase. We introduce a new method to screen for optimal microcrystallization conditions suitable for use in serial crystallography and present a number of RT ligand-bound structures of our target protein. From a comparison between the RT structural data and previously published cryo-temperature structures, we describe an example of a temperature-dependent difference in the ligand-binding mode and observe that flexible loops are better resolved at RT. Finally, we discuss the current limitations and potential future advances of serial crystallography for use within pharmaceutical drug discovery.

The structures of three multicomponent crystals formed with imidazole-based drugs, namely metronidazole, ketoconazole and miconazole, in conjunction with tri­thio­cyanuric acid are characterized. Each of the obtained adducts represents a different category of crystalline molecular forms: a cocrystal, a salt and a cocrystal of salt. The structural analysis revealed that in all cases, the N—H⋯N hydrogen bond is responsible for the formation of acid–base pairs, regardless of whether proton transfer occurs or not, and these molecular pairs are combined to form unique supramolecular motifs by centrosymmetric N—H⋯S interactions between acid molecules. The complex intermolecular forces acting in characteristic patterns are discussed from the geometric and energetic perspectives, involving Hirshfeld surface analysis, pairwise energy estimation, and natural bond orbital calculations.

The crystal structure of the tetra­ethyl­ammonium salt of the non-steroidal anti-inflammatory drug nimesulide (polymorph II) (systematic name: tetra­ethyl­ammonium N-methane­sulfonyl-4-nitro-2-phen­oxy­anilinide), C8H20N+·C13H11N2O5S−, was determined using single-crystal X-ray diffraction. The title compound crystallizes in the monoclinic space group P21/c with one tetra­ethyl­ammonium cation and one nimesulide anion in the asymmetric unit. In the crystal, the ions are linked by C—H⋯N and C—H⋯O hydrogen bonds and C—H⋯π inter­actions. There are differences in the geometry of both the nimesulide anion and the tetra­ethyl­ammonium cation in polymorphs I [Rybczyńska & Sikorski (2023). Sci. Rep. 13, 17268] and II of the title compound.

When a promising new drug to treat obesity was approved by the Food and Drug Administration for sale in the U.S. last month, it was the first such treatment to gain approval since 2014.

In clinical trials, weekly injections of semaglutide — or Wegovy, as it's been branded -- helped people drop an average of 15% of their body weight. That's an average of about 34 pounds over 16 months, before their weight plateaued, a far greater weight loss, obesity specialists say, than achieved with other drugs on the market. At least as important, Wegovy raised none of the alarm bells with the FDA or obesity doctors that it might trigger serious side effects of the sort experienced by some people taking fen-phen or some previous medical treatments for obesity.

But with a price tag for Wegovy of $1,000 to $1,500 a month, a very big question remains: Will insurers cover its significant cost for the many millions of people like Marleen Greenleaf, who might benefit?

Greenleaf grew up on the island of Trinidad, where her entire family paid little heed to what they ate and paid a high medical price, she says: "My husband has diabetes, my sister has diabetes, my brother has diabetes."

Since then, she's tried — and failed — at numerous diets, says Greenleaf, now 58 and an administrator at a charter school in Washington, D.C. Then, in 2018, she signed up for the clinical trial of a new drug — a once-weekly shot that changes the way her brain signals hunger.

A drug that finally stops her cravings

She noticed the change soon after her first injection of Wegovy: "For me, there was something that triggered in my brain to tell me that I was not hungry," she says. No more fierce cravings for the chocolate chip cookies she adores. Without the cravings she was able to slow down and reconsider the foods she'd been reaching for.

"I also wanted to eat healthier," she says. "I was looking at options, reading labels, looking at the calories — not just the calories, but also the sugar."

Over the 68-week research trial, Greenleaf dropped 40 pounds. Her blood pressure fell, which meant she qualified to donate her kidney to her husband, who was on dialysis.

"It was one of the best gifts of life that I could have ever given," she says.

But after that study ended, Greenleaf regained some of the weight. Wegovy is considered a long-term, possibly lifelong medication to treat chronic obesity. In the pre-marketing clinical studies, weight loss topped out at a total average weight loss of 15-18%, even as people continued to take the drug. And, as was the case with Greenleaf, once they stopped getting the weekly injections some of that weight came back.

Now, Greenleaf wants to resume the Wegovy shots.

"My only challenge actually is getting the insurance company to approve it," she says.

Reimbursement for obesity drugs' cost is patchy

Insurance coverage, it turns out, is a giant question — not just with Wegovy, but with obesity drugs in general. Some private insurers do include some prescription obesity drugs in the list of medicines they'll cover; it's too early to tell whether Wegovy will make those lists. Many doctors and patients are optimistic, because it is a higher dose of an existing diabetes medication called Ozempic, which is often covered by insurers.

A few select state Medicaid programs will cover medications that treat obesity, in some circumstances. But, significantly, Medicare does not cover obesity drugs — and many private insurers typically follow Medicare's lead.

Yet the demand for a good treatment is there, says Dr. Fatima Cody Stanford, a leading obesity researcher at Harvard. She was not involved in conducting the Wegovy clinical trial, but closely followed it. "I'm excited about it," she says, because of the dramatic weight loss.

The drug acts on the brain so people eat less and store less of what they eat. That helps address the excess weight as well as helping with numerous related diseases of the liver or heart, for example.

Why the FDA has been slow to approve obesity treatments

There is a long history of drugs that have looked like promising treatments for obesity, then failed. Decades ago, amphetamines, were prescribed, until their addictive properties became apparent. In the 1990s, the combination of fenfluramine and phentermine — administered as the diet drug fen-phen — was heavily marketed, only to later be pulled from the market for causing heart valve problems.

Those experiences and others have made physicians skeptical.

"In obesity medicine field, we've learned to be cautiously optimistic each time we have a new medication that looks promising," says Dr. Ihuoma Eneli, director of the Center for Healthy Weight and Nutrition at Nationwide Children's Hospital in Columbus, Ohio, who was not involved in the study of Wegovy.

So far, Eneli does not see any obvious concerns with the class of drugs that includes Wegovy, and calls the results so far "very promising." Wegovy is similar to another drug made by Novo Nordisk — Saxenda — which has been on the market since 2014, and which Eneli occasionally prescribes to her pediatric patients who are struggling with obesity.

In clinical research studies, the primary side effects reported after taking Wegovy affected the digestive system: nausea, diarrhea, vomiting, constipation, abdominal pain or intestinal infections.

Eneli says such side effects and their frequency are milder than the problems that have arisen in the past. That good safety profile may mean the drug is "less likely to come up with unanticipated risks," she says.

But, the new drug will be of little use, she and other doctors who treat obesity say, if it's not also affordable for patients.

"Before I even bring up that drug with my patients, I'm looking to see which insurance they are having on the left side of my screen — because that will determine whether I bring it up," Stanford, the Harvard physician, says. "If it's out of reach, like I said, I won't bring it up."

Stanford says her patients on existing obesity medications do extraordinary things to keep their coverage so they can afford to stay on the drugs.

"Several nurses here at the hospital that are my patients stayed working — they were supposed to retire — so they could stay on their injectable medication," Stanford says,"because that's how beneficial it was to them."

Why some are willing to pay out of pocket

Some people, like David Scheesley, 42, says he would consider paying for Wegovy, even if he had to pay the full sticker price. The Hanford, Calif., correctional officer has tried since 2019 to lose weight on various diets — low-fat, all-meat, all-vegetable — without success. His weight has led to other health concerns — with his blood fats and his heart — which makes Scheesley think of his 5-year-old son.

"I want to see him for a lot of years; I don't want to have a stroke," he says. "I don't want to have diabetes. I want to be there for him. So, for me personally, that [monetary cost] is not astronomical, if it can give me some more time."

Novo Nordisk, the company that makes Wegovy, is in talks with insurers, and acknowledges that ensuring health insurance coverage of its drug is critical. The challenge, says Douglas Langa, executive vice president of Novo Nordisk North America, is getting doctors, patients, and politicians to recognize obesity as a disease — and that therefore insurance should cover the cost of medicine to treat it.

"There's a medical component to [obesity] that needs to be recognized; this is a disease state like we should be treating any other disease state," Langa says. He says about 40% of private insurers cover Saxenda, the similar weight-loss medication the company makes.

Langa tells insurance companies this, making the case for why prescriptions for Wegovy should be covered. His company is also heavily lobbying Congress to pass legislation to allow Medicare to cover obesity medications. It makes sense from a financial perspective, he argues, because obesity is the root disease underlying so many other diseases.

"We do believe insurers understand that [untreated obesity] is a gateway into 60 other health conditions," Langa says. The need is hard to ignore, he adds. More than 100 million people in the U.S. alone struggle with obesity.

This content is from Southern California Public Radio. View the original story at SCPR.org.

The U.S. Supreme Court has ruled that low-level crack cocaine offenders cannot benefit from a 2018 federal law.; Credit: J. Scott Applewhite/AP

The U.S. Supreme Court ruled Monday that some crack cocaine offenders sentenced to harsh prison terms more than a decade ago cannot get their sentences reduced under a federal law adopted with the purpose of doing just that.

At issue in the case was the long and now notorious history of sentencing under the 1986 Anti-Drug Abuse Act, which established harsh mandatory prison sentences based on the amount of drugs that the defendant possessed or sold. The triggering amount, however, was different for crack cocaine used most often by Black people, and powder cocaine, used most often by whites.

Indeed, the ratio was 100-to-1, so that a five-year mandatory minimum penalty, for instance, was triggered by possession of 5 grams of crack, whereas the same penalty was triggered by 500 grams of powder cocaine.

Nine years after enactment of these mandatory penalties, the U.S. Sentencing Commission found these disparities unjustified, and by 2010 Congress passed new legislation to reduce the disparity to from 100-to-1 to 18-to-1. But that left everyone previously sentenced under the old regime stuck with the harsher penalties. And in 2018, Congress passed and then-President Donald Trump signed into law a bipartisan bill to make the new ratios retroactive.

That allowed thousands of crack offenders who were serving prison sentences to be resentenced under the new law and new sentencing guidelines, with an average reduction of six years in their sentences. But while the new law allowed even drug kingpins to be resentenced, some prisoners were left out — a number now in the low hundreds, according to the Biden administration.

One of those was the prisoner at the center of Monday's case, Tarahrick Terry, sentenced to nearly 16 years in prison for possession with intent to distribute 3.9 grams of crack cocaine, less than the weight of four paper clips.

He claimed that his sentence, like others, should be revised in light of the 2018 law, but the Supreme Court rejected that argument. Writing for the court, Justice Clarence Thomas noted that Terry had been sentenced under a section of the law that applied to "career criminals," those who had two previous drug or violent convictions. Terry did, in fact, have two previous drug convictions as a teenager — for which he spent 120 days in jail.

So, as Thomas observed, Terry was sentenced under the provision of the law that was not included in the 2018 revision.

Democratic Sens. Dick Durbin and Cory Booker and Republican Sens. Charles Grassley and Mike Lee — the sponsors and drafters of the act — warned in a friend of the court brief filed in the case that excluding low-level offenders from the act's reforms would mean ignoring its purpose. "Had Congress intended to exclude individuals with low-level crack offenses from relief," they wrote, "Congress of course could have done so."

Thomas and the rest of the court rejected that argument. "We will not convert nouns to adjectives and vice versa," wrote Thomas, which is what he said Congress was asking the court to do. The 2018 law, he said, did not change the section of the law under which Terry was sentenced, so the argument that the revision modified the whole law just wouldn't wash.

Although the decision was unanimous, it included an interesting back-and-forth about race between Thomas, the only African American on the court and arguably its most conservative member, and Justice Sonia Sotomayor, its only Hispanic and arguably most liberal member. Specifically, their disagreement was about the role race played in the adoption of mandatory minimum sentences that were wildly more harsh for possession or sale of crack cocaine than for powder cocaine.

As Thomas saw it, the 100-to-1 ratio for crack cocaine was enacted "with near unanimity" by Congress, because of two concerns expressed by Black leaders at the time: First, that crack "was fueling crime against residents in the inner cities who were predominantly black," and second that "prosecutors were not taking these kinds of crimes seriously enough because the victims were disproportionately black." Moreover, he quoted a 1995 U.S. Sentencing Commission report that concluded the 100-to-1 ratio created "a perception of unfairness," even though there was no reason to believe that "racial bias or animus undergirded the initiation of the federal sentencing law."

In a concurring opinion, Sotomayor declined to join that part of Thomas' opinion, because "it includes an unnecessary, incomplete, and sanitized history of the 100-to-1 ratio," including "race-based myths" about crack cocaine.

"The full history is far less benign," she said. It ignores the fact that Black leaders were promised federal investment in longer term solutions — including in job training and education programs — but that help never arrived. Nor, she noted, did the majority opinion mention that the bill containing the 100-to-1 ratio was "rush[ed] through to pass dramatic drug legislation before the midterm elections," and that the legislative history of the bill offered no justification for the 100-to-1 ratio, "save that it was the highest ratio proposed."

"Most egregiously, the Court barely references the ratio's real-world impact" — one so profound and unjustified, as demonstrated by subsequent research — "that the [Congressional Black Caucus] came together in unanimous and increasingly vocal opposition to the law."

In the end, however, Sotomayor agreed that "unfortunately," the reading of the law urged by the primary sponsors of the 2018 revision is not born out by the text. "Fortunately," she added, "Congress has numerous tools to right this injustice."

As for prisoner Terry, who brought Monday's case, he is now in the final months of his prison term, and according to the Biden administration is serving his remaining time in home confinement.

This content is from Southern California Public Radio. View the original story at SCPR.org.

Marijuanas active components are potentially effective in treating pain, nausea, the anorexia of AIDS wasting, and other symptoms, and should be tested rigorously in clinical trials.

Medication errors are among the most common medical errors, harming at least 1.5 million people every year, says a new report from the Institute of Medicine of the National Academies.

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The goal of achieving universal health coverage by 2030 — one of the United Nations’ Sustainable Development Goals — necessitates that countries strengthen their food and drug regulatory systems as a whole, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Although the immediate side effects of antimalarial drugs are widely recognized, few studies were designed specifically to examine health problems that might occur or persist months or years after people stopped taking them.

Every year, significant amounts of drugs left over and unused from single-dose vials are discarded, but because of the way drugs are priced and paid for in the United States, the cost of the discarded amount cannot be recouped, says a new congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

Science academies from the G-7 nations issued statements urging their governments to take action on four global challenges — developing antiviral drugs to prepare for future pandemics, speeding progress on decarbonization, protecting the oceans and sea ice, and implementing a One Health approach to zoonotic disease and antimicrobial resistance.

The COVID-19 pandemic shined a spotlight on the continuing, decades-long problem of medical product supply chain disruptions. Drug and medical device shortages — life-threatening for some — also affect the entire U.S health care system, costing millions of dollars annually. New resources from the National Academies offer insights.

Liquid crystals are strange substances, both fish and fowl. They can flow like a liquid, but have the orderly molecular structure of a crystalline solid. And that internal structure can be changed by small cues from outside.

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In a creative stroke inspired by Hollywood wizardry, scientists from Harvard Medical School and Technion-Israel Institute of Technology have designed a simple way to observe how bacteria move as they become impervious to drugs.

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The analysis of nearly 10 million drug tests reveals a surge in cheating, particularly related to marijuana.

Inflation has accelerated the trend of higher-income consumers shopping at dollar stores, experts report.

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NationDrugs.to introduces a reliable solution for patients searching for affordable and high-quality generic cancer drugs.

NationDrugs.to remains a trusted source for affordable medications and continues to serve customers across the globe who are seeking a cost-effective solution to their healthcare needs.

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By Offering Safe and Reliable Access to Low-Cost Medications from Canadian Pharmacies, SaveRxCanada.to Provides Critical Support for Seniors Struggling with High Prescription Costs in the U.S.

Dr. Beyza Bulutoglu channels years of expertise into her work with Genentech Inc.

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Harriet Hunter's award-winning, bestselling book became the first-place recipient of the coveted President's Award in nonfiction from the Florida Authors and Publishers Association. Miracles features 365 powerful daily inspirations

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CD BioSciences recently announced the release of its high-quality, cost-effective C. elegans pharyngeal pumping analysis services for drug screening.

The 18th Annual Pain Therapeutics Summit, a premier event bringing together leading experts in pain research and therapeutics, will take place from October 28th, 2024 to October 29th, 2024 in Boston, Massachusetts.

Alfa Cytology has introduced its advanced drug development services for brain tumors.

The US Drug Watchdog says, "If a person orders 'Ozempic' from an offshore online pharmacy, there is a very-very good chance the medication will not work-and in the worst-case scenario the drug might be fatal-or cause extremely severe side effects."

Nation's First Lawsuit Asserting that the Affordable Care Act Forbids Exclusion of Obesity Treatment

QueenNAK aims to promote Entertainment, Business and cultural exchange between Africa and the United States. She will be donating a portion of the funds raised from the album launching to the government of Sierra Leone to assist the drug victims.

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The Pennsylvania Supreme Court has granted review of disagreement over the proper prescription drug fee schedule for resolving workers’ compensation disputes. In January, the Commonwealth Court held that Red Book values…