Prodrug not its intended target. This reduces adverse or unintended effects of a drug, especially important in treatments like chemotherapy, which can have severe unintended and undesirable side effects. Many herbal extracts historically used in medicine contain glycosides (sugar derivatives) of the active agent, which are hydrolyzed in the intestines to release the active and more bioavailable aglycone. For example, salicin is a β-D-glucopyranoside that is cleaved by esterases to release salicylic acid. Aspirin, acetylsalicylic acid, first made by Felix Hoffmann at Bayer in 1897, is a synthetic prodrug of salicylic acid. However, in other cases, such as codeine and morphine,
U Should've Known Better song entered the "Billboard" Hot 100 chart, where it debuted at number 67 in the week of June 6, 2004, the second-highest debut of the week. "U Should've Known Better" remained twenty weeks on the chart, reaching its peak position of number 19 in its ninth week. It marked the second single from "After the Storm" to reach the top twenty on the Hot 100chart and, as the album's final single, would remain its second highest-charting offering behind leading single "So Gone." Although never released on a CD single or CD maxi single format, "U Should've Known Better" was also