A second, less deadly outbreak occurred in 1920–21, killing approximately 9,300 people.The Peoples Republic of China has eradicated pneumonic plague from most parts of the country, but still reports occasional cases in remote western areas, where the disease is carried by rats and the marmots that live across the Himalayan plateau. Outbreaks can be caused when a person eats an infected marmot or comes into contact with fleas carried by rats. A 2006 WHO report from an international meeting on plague cited a Chinese government disease expert as saying that most cases of the plague in Chinas northwest occur when hunters are contaminated while skinning infected animals.The expert said at the time that, due to the regions remoteness, the disease killed more than half the infected people. The report also said that since the 1990s, there was a rise in plague cases in humans—from fewer than 10 in the 1980s to nearly 100 cases in 1996 and 254 in 2000. In September 2008, two people in East Tibet died of pneumonic plague.An outbreak of the disease in China began in August 2009 in Ziketan Town located in Qinghai Province. The town was sealed off and several people died as a result of the disease. According to spokesperson Vivian Tan of the WHO office in Beijing, "In cases like this [in August 2009], we encourage the authorities to identify cases, to investigate any suspicious symptoms among close contacts, and to treat confirmed cases as soon as possible. So far, they have done exactly that.
Asciminib, sold under the brand name Scemblix, is a medication used to treat Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). Asciminib is a protein kinase inhibitor.The most common adverse reactions include upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea.Asciminib was approved for medical use in the United States in October 2021, and in the European Union in August 2022.The U.S. Food and Drug Administration (FDA) granted the application for asciminib priority review, fast track, orphan drug, and breakthrough therapy designations. Mechanism of action
Asciminib is described as a "STAMP inhibitor," which means "specifically targeting the ABL myristoyl pocket." The wild-type ABL has a myristoylated N-terminus, which binds to an allosteric site, but the ABL fusion protein does not have the myristoylated domain. In the wild-type protein, when myristoylated N-terminus binds to the allosteric site, the kinase has reduced activity. Since the mutant fusion protein does not have the myristoylated N-terminus domain, it is not subject to this form of regulation, and thus the fusion protein is constitutively active. Asciminib binds to the allosteric site, resulting in an inhibition of bcr-abl activity.Unlike other bcr-abl inhibitors, such as imatinib, asciminib does not bind to the ATP-binding site on the active site of the enzyme. Asciminib and active site bcr-abl inhibitors have non-overlapping resistance mutations. The mutations A337V and P223S overcome the inhibitory activity of asciminib, but asciminib is not affected by the notorious T315I mutation that affects most ATP-competitive active site inhibitors, except ponatinib.