Gaedcke named the alkaloid "erythroxyline", and published a description in the journal Archiv der Pharmazie.In 1856, Friedrich Wöhler asked Dr. Carl Scherzer, a scientist aboard the Novara (an Austrian frigate sent by Emperor Franz Joseph to circle the globe), to bring him a large amount of coca leaves from South America. In 1859, the ship finished its travels and Wöhler received a trunk full of coca. Wöhler passed on the leaves to Albert Niemann, a PhD student at the University of Göttingen in Germany, who then developed an improved purification process.Niemann described every step he took to isolate cocaine in his dissertation titled Über eine neue organische Base in den Cocablättern (On a New Organic Base in the Coca Leaves), which was published in 1860 and earned him his Ph.D. He wrote of the alkaloids "colourless transparent prisms" and said that "Its solutions have an alkaline reaction, a bitter taste, promote the flow of saliva and leave a peculiar numbness, followed by a sense of cold when applied to the tongue." Niemann named the alkaloid "cocaine" from "coca" (from Quechua "kúka") + suffix "ine".The first synthesis and elucidation of the structure of the cocaine molecule was by Richard Willstätter in 1898. It was the first biomimetic synthesis of an organic structure recorded in academic chemical literature. The synthesis started from tropinone, a related natural product and took five steps. Because of the former use of cocaine as a local anesthetic, a suffix "-caine" was later extracted and used to form names of synthetic local anesthetics.
Glasdegib, sold under the brand name Daurismo, is a medication for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults older than 75 years or those who have comorbidities that preclude use of intensive induction chemotherapy. It is taken by mouth and is used in combination with low-dose cytarabine.The recommended dose of glasdegib is 100 mg orally once daily on days 1 to 28 in combination with cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle in the absence of unacceptable toxicity or loss of disease control.The most common adverse reactions are anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.It is a small molecule inhibitor of sonic hedgehog, which is a protein overexpressed in many types of cancer. It inhibits the sonic hedgehog receptor smoothened (SMO), as do most drugs in its class. History
Glasdegib was approved for medical use in the United States in December 2018.FDA approval was based on a multicenter, open-label, randomized study (BRIGHT AML 1003, NCT01546038) that included 115 subjects with newly-diagnosed AML who met at least one of the following criteria: a) age 75 years or older, b) severe cardiac disease, c) baseline Eastern Cooperative Oncology Group performance status of 2, or d) baseline serum creatinine >1.3 mg/dL.