Disease relevance of Didemnin D

• Didemnin B was more potent than was didemnin A against B16 melanoma and P388 leukemia in vivo, and B was also approximately 20 times more cytotoxic than was didemnin A in vitro [1].
• Inhibition of RNA viruses in vitro and in Rift Valley fever-infected mice by didemnins A and B [2].
• A phase II study of Didemnin B (NSC 325319) in advanced malignant melanoma: an Eastern Cooperative Oncology Group study (PB687) [3].
• Phase II clinical trial of didemnin B in patients with recurrent or refractory anaplastic astrocytoma or glioblastoma multiforme (NSC 325319) [4].
• Didemnins A and B. Effectiveness against cutaneous herpes simplex virus in mice [5].

High impact information on Didemnin D

• The cytotoxicity to different cell lines and inhibition of macromolecule synthesis by didemnin A is also reported [1].
• Interestingly, the set of interactions used by didemnins to bind to eEF1A is also distinct from that used by eEF1Balpha or eEF1Bbeta, thus establishing a competition for binding to a common site that goes beyond simple molecular mimicry [6].
• Didemnins and tamandarins are closely related marine natural products with potent inhibitory effects on protein synthesis and cell viability [6].
• Didemnin B is currently in Phase II clinical trials as an anticancer agent, and the antineoplastic activity, as well as the antiviral and immunosuppressive activities, of the didemnins are reviewed [7].
• Eight times this level of didemnin A could be administered before similar toxicity was observed [5].

Biological context of Didemnin D

• In the GDP-bound form of eEF1A, this binding site exists only as two separate halves, which accounts for the much greater affinity of didemnins for the GTP-bound form of this elongation factor [6].
• The molecular structure of didemnin A, the parent compound of a series of antiviral cytotoxic depsipeptides extracted from a marine tunicate Trididemnum solidum of the family of Didemnidae, has been determined by single-crystal X-ray diffraction [8].

Analytical, diagnostic and therapeutic context of Didemnin D

• Immunosuppressive activity of the didemnins was determined using a mixed lymphocyte reaction (MLR) assay [9].

References