Superheroes of Chemistry: From Lab to Life
This past summer brought in a wave of superhero movies that featured mysterious kings, alien demigods, reformed burglars, and more. But no chemists.
Fortunately, ACS capped off the season by announcing Heroes of Chemistry for 2018. For 22 years, the program has honored industrial chemists whose innovations have the greatest impact on our society. inChemistry is taking a closer look at the ingenuity, creativity, and perseverance of this year's "superchemists" who have paved the way for us all to live healthier, greener lives.
Defeating the mutating villain
The supervillain, Ultron, is a robot that constantly upgrades himself—so much so, the Avengers needed to add teammates to take him down. Like Ultron, cancer cells frequently mutate into tougher forms that require new drugs to defeat them. For example, non-small cell lung carcinoma, which accounts for 85% of all lung cancer cases, is first triggered by a mutation in lung cells. This mutation overstimulates cell epidermal growth factor receptors (EGFRs). These receptors control the growth of healthy tissue, but when they are overstimulated, they promote out-of-control tumor growth. While treatments for these tumors already exist, many non-small cell carcinoma patients develop an additional mutation, T790M, which results in highly drug-resistant tumor cells.
Enter Sam Butterworth, Ray Finlay, Richard Ward, and Michael Waring of AstraZeneca. The team looked at the structure of drugs known to inhibit tumor growth to develop osimertinib, a drug that selectively targets T790M without harming healthy cells.
Marketed under the brand name Tagrisso, osimertinib was synthesized in June 2011. The first human trials occurred in March 2013, and the drug gained regulatory approval in November 2015. For cancer treatments, this is an exceptional development speed that gives hope to patients with drug-resistant tumors.
TAGRISSO (osimertinib) is a novel, targeted treatment for patients with EGFR-mutated non-small cell lung cancer. Osimertinib is approved in more than 75 countries.
Building better solar cells
Thor can use lightning to generate all the power he needs, but humans are increasingly looking for solar solutions. Over the past eight years, the U.S. capacity for solar energy has increased by 23 times. Commercial use of solar voltaic cells use rely on crystalline silicon wafers coated with Si3N4 (an antireflective coating) to convert light from the sun into current and voltage to generate power. Thin lines of silver metal placed on the surface of the silicon act as wires to transport the electricity to where it is needed.
Alan Carroll, Kenneth Hang, Brian Laughlin, Kurt Mikeska, Charlie Torardi, and Paul VerNooy at DuPont have been developing “metallization pastes” to apply the silver lines. Metallization pastes are a blend of sliver particles, organic binders, and glass frit. The paste is applied to the silicon wafer and briefly heated. The heat is enough for the glass to melt and etch away some of the Si3N4, while the silver particles sinter together, adhering to the underlying silicon to form wires.
The biggest challenge in the process is creating a silver-silicon contact that doesn’t damage the crystalline structure of the wafer. The DuPont team has developed Solamet PV17x, a game-changing lead tellurite metallization paste that not only protects the wafer, but also improves the conversion of solar light to useable electricity.
Since its release, the team continues to improve the Solamet technonology. With more powerful and cost-effective wafers available, DuPont’s researchers are helping secure a future of solar energy.
Solamet PV17x is the metallization paste that pioneered the use of lead tellurite chemistry, a game changer in the solar energy industry.
Blocking blood-hungry tumors
In the movies, Blade is a martial arts master who relies on a serum to prevent him from succumbing to the bloodlust inherited from his vampire father. He might have learned a thing or two from Pfizer’s Steve Bender, John Braganza, Anthony Campeta, Brian Chekal, Stephan Cripps, Michael R. Collins, Steven Guinness, Robert Kania, Michele McTigue, Cindy Palmer, Robert Singer, Jayaram Srirangam, Mike Varney, Shu Yu, and Scott Zook. This superteam developed axitinib, a cancer treatment that prevents tumors from growing their own blood supply. Specifically, the drug attaches to vascular endothelial growth factors (VGEFs), a subset of enzymes that tumors use to promote angiogenesis, the growth of blood vessels. Because tumors rely on blood vessels to help them grow, blocking VGEFs stops the growth of tumors and prevents their spread to the rest of the body.
Marketed under the brand name Inlyta, axitinib is a lifesaver for kidney cancer patients. Nine out of 10 kidney cancer diagnoses are renal cell carcinoma, and more than 30% have already metathesized (spread) by the time they are diagnosed. These metastatic tumors are notoriously resistant to standard chemotherapy, with a mere 8% survival rate for patients in Stage IV of the disease.
But thanks to the Pfizer team and their axitinib super-serum, renal cancer patients have a better chance of defeating the disease.
Inlyta (axitinib) is a standard of care for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy.
Nailing the trick shot
Hawkeye is best known for his perfect targeting skills, but even he would have trouble nailing a specific protein on a Hodgkin’s lymphoma tumor cell. Luckily, we have Tim Bovee, Svetlana Doronina, Brian Mendelsohn, Peter Senter, Clay Siegall, and Brian Toki of Seattle Genetics making those shots.
The Seattle Genetics team developed brentuximab vedotin, marketed as ADCETRIS, a new type of drug treatment called antibody-drug conjugate (ADC). An ADC is pretty much what it sounds like—a drug molecule and antibody molecule linked together.
In Adcetrisa, the drug monomethylauristatin E (MMAE) is linked to CD30, an antibody protein found in Hodgkin’s lymphoma cells but not healthy ones. Once injected, ADC latches onto CD30 receptors on the surface of the tumors. It is then absorbed into the cell where it breaks down, releasing the potent MMAE and killing the cell. Because healthy cells don’t have CD30 (or its receptors), they are untouched.
Adcetrisa received accelerated FDA approval in 2011, paving the way for other ADCs that can target tumors with pinpoint accuracy. Since then, four more ADCs have been approved, and 55 are in clinical trials.
ADCETRIS (brentuximab vedotin) uses the company’s industry-leading antibody-drug conjugate (ADC) technology and is currently approved for the treatment of multiple CD30-expressing lymphomas.
inChemistry congratulates the 2018 Heroes of Chemistry and eagerly awaits the 2019 sequel!