The Press-Dispatch
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'Undruggable' cancer protein becomes druggable A chemist from Purdue University has found a way to synthesize a compound to fight a previously "undrugga- ble" cancer protein with ben- efits across a myriad of can- cer types. Inspired by a rare com- pound found in a shrub native to North America, Mingji Dai, professor of chemistry and a scientist at the Purdue Uni- versity Center for Cancer Re- search, studied the compound and discovered a cost-effec- tive and efficient way to syn- thesize it in the lab. The com- pound — curcusone D — has the potential to help combat a protein found in many can- cers, including some forms of breast, brain, colorectal, prostate, lung and liver can- cers, among others. The pro- tein, dubbed BR AT1, had pre- viously been deemed "undrug- gable" for its chemical prop- erties. In collaboration with Alexander Adibekian's group at the Scripps Research Insti- tute, they linked curcusone D to BR AT1 and validated cur- cusone D as the first BR AT1 inhibitor. Curcusones are compounds that come from a shrub named Jatropha curcas, also called the purging nut. Native to the Americas, it has spread to oth- er continents, including A frica and Asia. The plant has long been used for medicinal prop- erties — including the treat- ment of cancer — as well as being a proposed inexpensive source of biodiesel. Dai was interested in this family of compounds — cur- cusone A, B, C and D. "We were very interested by these compounds' novel struc- ture," Dai said. "We were in- trigued by their biological function; they showed quite potent anti-cancer activity and may lead to new mechanisms to combat cancer." Researchers tested the compounds on breast cancer cells and found curcusone D to be extremely effective at shutting down cancer cells. The protein they were target- ing, BR AT1, regulates DNA damage response and DNA repair in cancer cells. Can- cer cells grow very fast and make a lot of DNA. If scien- tists can damage cancer cells' DNA and keep them from re- pairing it, they can stop can- cer cells from growing. The research was recently pub- lished in the Journal of the American Chemical Society. Mingji Dai, professor of or- ganic chemistry at Purdue University. (Purdue Univer- sity photo/Charles Jischke) Download image "Our compound can not only kill these cancer cells, it can stop their migration," Dai said. "If we can keep the can- cer from metastasizing, the patient can live longer." Stopping cancer from spreading throughout the body — metastasizing — is key to preserving a cancer pa- tient's life. Once cancer starts to migrate from its original or- gan into different body sys- tems, new symptoms start to develop, often threatening the patient's life. "For killing cancer cells and stopping migration, there are other compounds that do that," Dai said. "But as far as inhibiting the BR AT1 protein, there are no other compounds that can do that." Dai and his team believe that as effective as curcusone D is by itself, it may be even more potent as part of a com- bination therapy. They test- ed it alongside a DNA dam- aging agent that has already been approved by the Food and Drug Administration and found that this combination therapy is much more effec- tive. One difficulty in studying curcusones as potential can- cer treatments is that, while the shrub they come from is common and inexpensive, it takes massive amounts of the shrub to yield even a small amount of the compounds. Even then, it is difficult to separate the compounds they were interested in from the rest of the chemicals in the shrub's roots. "In nature, the plant doesn't produce a lot of this com- pound," Dai said. "You would need maybe as much as 100 pounds of the plant's dry roots to get just about a quarter tea- spoon of the substance — a 0.002 % yield." That small yield is relevant for production, because if it is effective as a cancer treat- ment, pharmacists will need a lot more of it. Additionally, having an abundant supply of the compounds makes study- ing them easier, quicker and less expensive. "That's why a new synthe- sis is so important," Dai said. "We can use the synthesis to produce more compounds in a purer form for biological study, allowing us to advance the field. From there, we can make analogs of the com- pound to improve its potency and decrease the potential for side effects." The next step will be to test the compound to ensure that it is not toxic to humans, something the researchers are optimistic about since the shrub it came from has been used as a traditional medi- cine in a number of cultures. Already, researchers from other entities have reached out to test the compound on the cancers they study, bring- ing hope for renewed thera- peutics for treating the dis- ease. "Many of our most success- ful cancer drugs have come from nature," Dai said. "A lot of the low-hanging fruit, the compounds that are easy to isolate or synthesize, have already been screened and picked over. We are looking for things no one has thought about before. Once we have the chemistry, we can build the molecules we're interest- ed in and study their biologi- cal function." Mingji Dai, professor of organic chemistry at Purdue University. Curcusone D, the first synthesized BR AT-1 inhibitor, originally comes from the root of Jatropha curcas, a shrub native to the Americas. A-6 Wednesday, May 5, 2021 The Press-Dispatch Harrison-Davis Marissa Rochelle Harri- son, formerly of Illinois, and Stuart Pendleton Davis, for- merly of Tulsa, Okla., were married April 24, 2021, at Camp Illiana by John Paul Howard, Marissa's uncle. There was a reception fol- lowing the ceremony. The bride's son, Wesley Que, was ring bearer. She is the daughter of Cindy and Mike Harrison. The groom's parents are Russell and Denise Davis. The couple now resides in Petersburg. MARRIAGE LICENSES Brandon DeWayne Green, 33, of 6633 E. CR 1150, Stendal, son of Dar- rell M. Green and Leann Lacasse, to Jenny Jean Meyerholtz, 33, of 6633 E. CR 1150, Stendal, daugh- ter of Rick and Debbie Meyerholtz. Johnny Darrell Long, 35, of 293 N. SR 61, Winslow, son of Johnny Long and Catherine Shel- ton, to Korie Alexandra Poselwait, 31, of 293 N. SR 61, Winslow, daughter of Leon Smith and Tina Up- pencamp. With This Ring.. The whitest paint is here – and it's the coolest. Literally. In an effort to curb glob- al warming, Purdue Univer- sity engineers have created the whitest paint yet. Coat- ing buildings with this paint may one day cool them off enough to reduce the need for air conditioning, the re- searchers say. In October, the team cre- ated an ultra-white paint that pushed limits on how white paint can be. Now they've outdone that. The newer paint not only is whiter but also can keep surfaces cool- er than the formulation that the researchers had previ- ously demonstrated. "If you were to use this paint to cover a roof area of about 1,000 square feet, we estimate that you could get a cooling power of 10 kilo- watts. That's more power- ful than the central air con- ditioners used by most hous- es," said Xiulin Ruan, a Pur- due professor of mechanical engineering. An infrared camera shows how a sample of the whitest white paint (the dark purple square in the middle) actu- ally cools the board below ambient temperature, some- thing that not even commer- cial "heat rejecting" paints do. (Purdue University/Jo- seph Peoples) Download im- age The researchers believe that this white may be the closest equivalent of the blackest black, "Vantab- lack," which absorbs up to 99.9 % of visible light. The new whitest paint formula- tion reflects up to 98.1% of sunlight – compared with the 95.5% of sunlight reflect- ed by the researchers' previ- ous ultra-white paint – and sends infrared heat away from a surface at the same time. Typical commercial white paint gets warmer rather than cooler. Paints on the market that are designed to reject heat reflect only 80 % - 90 % of sunlight and can't make surfaces cooler than their surroundings. The team's research pa- per showing how the paint works publishes Thursday (April 15) as the cover of the journal ACS Applied Materi- als & Interfaces. What makes the whitest WHITE Xiulin Ruan, a Purdue University professor of mechanical engineering, holds up his lab's sample of the whitest paint on record. 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