▁ ▁Then ▁the ▁ 5 ' ▁hydro x yl ▁end ▁of ▁the ▁broken ▁DNA ▁str and ▁can ▁reverse ▁the ▁ph osph oty ros yl ▁bond , ▁en abling ▁the ▁release ▁of ▁T OP 1 ▁and ▁relig ation ▁of ▁the ▁DNA . ▁ ▁The ▁nick ing ▁and ▁closing ▁re actions ▁are ▁fast , ▁and ▁about ▁ 1 0 0 ▁cycles ▁can ▁occur ▁per ▁second . ▁ ▁In hib ition ▁ ▁The ▁briefly ▁attached , ▁c oval ently ▁bond ed ▁T OP 1 - D NA ▁structure ▁at ▁the ▁ 3 ' ▁end ▁of ▁a ▁cle aved ▁DNA ▁single ▁str and ▁is ▁called ▁a ▁T OP 1 - D NA ▁cle av age ▁complex , ▁or ▁T OP 1 cc . ▁ ▁The ▁T OP 1 cc ▁is ▁a ▁specific ▁target ▁of ▁T OP 1 ▁in hib itors . ▁ ▁One ▁of ▁the ▁first ▁in hib itors ▁shown ▁to ▁target ▁T OP 1 ▁is ▁ir in ot ec an . ▁ ▁Ir in ot ec an ▁is ▁an ▁analog ue ▁of ▁the ▁c yt ot ox ic ▁natural ▁al kal oid ▁cam pt othe cin , ▁obtained ▁from ▁the ▁Chinese ▁tree ▁Cam pt othe ca ▁ac umin ata . ▁ ▁Ir in ot ec an ▁is ▁especially ▁effective ▁through ▁its ▁met abol ic ▁product ▁SN - 3 8 . ▁ ▁Ir in ot ec an ▁and ▁SN - 3 8 ▁act ▁by ▁tra pping ▁a ▁subset ▁of ▁T OP 1 - D NA ▁cle av age ▁complex es , ▁those ▁with ▁a ▁gu an ine