Subsequent studies revealed that a single dose of CBX-12 resulted in a gradual, time-dependent release in exatecan in the tumor, with values maintained 2- to 3-fold above the IC50 for TOP1 depletion in vitro (24.8 nM), which persisted for 48 h, while an equimolar dose of unconjugated exatecan induced a rapid spike in drug levels in the tumor, which rapidly decreased below the in vitro IC50 for TOP1 depletion within 8 h (Figure 2E). Here, TOP1 is linked to neoplasm.