In some instances, clinical trials of the original natural
product may fail, but totally synthetic analogues continue
to be developed. Thus, while clinical trials of the marinederived
anti-cancer agents, dolastatin 10 (53; Scheme 12)
and dolastatin 15, have been terminated, synthetic analogues
are in various phases of clinical trials.146 Only auristatin PE
(TZT-1027 or soblidotin) (54; Scheme 12) is still in clinical
trials as the base molecule, and there are some very
interesting modifications that have been made by medicinal
chemists in order to deliver this close relative to dolastatin10
by use of monoclonal antibodies targeted at specific
epitopes.147,148 Currently, a significant number of combinations
of this base molecule with varying monoclonal antibodies
are in preclinical to phase II clinical trials predominately
against hematologic cancers
In some instances, clinical trials of the original natural
product may fail, but totally synthetic analogues continue
to be developed. Thus, while clinical trials of the marinederived
anti-cancer agents, dolastatin 10 (53; Scheme 12)
and dolastatin 15, have been terminated, synthetic analogues
are in various phases of clinical trials.146 Only auristatin PE
(TZT-1027 or soblidotin) (54; Scheme 12) is still in clinical
trials as the base molecule, and there are some very
interesting modifications that have been made by medicinal
chemists in order to deliver this close relative to dolastatin10
by use of monoclonal antibodies targeted at specific
epitopes.147,148 Currently, a significant number of combinations
of this base molecule with varying monoclonal antibodies
are in preclinical to phase II clinical trials predominately
against hematologic cancers
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