PM00104 (Zalypsis®): A Marine Derived Alkylating Agent

Petek, Bradley J.; Jones, Robin L.

doi:10.3390/molecules190812328

Cited by 29 publications

(19 citation statements)

References 25 publications

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“…H; Table ). Jorumycin displays GI 50 values in low nanomolar or even subnanomolar ranges in various cancer cells including cells resistant to proapoptotic stimuli . The high potency of jorumycin and the clinical successes of ecteinascidin led to intensive chemical modifications of jorumycin's chemical structure and this campaign thus resulted in PM00104 (Zalypsis®, 84b , Fig.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…The high potency of jorumycin and the clinical successes of ecteinascidin led to intensive chemical modifications of jorumycin's chemical structure and this campaign thus resulted in PM00104 (Zalypsis®, 84b , Fig. ) . Petek and Jones recently reviewed the preclinical and clinical data related to PM00104, which has entered several ongoing Phase II clinical trials.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…) . Petek and Jones recently reviewed the preclinical and clinical data related to PM00104, which has entered several ongoing Phase II clinical trials.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…In fact, ecteinascidin (trabectedin) has three isoquinolines, while the other two alkaloids have only two isoquinolines per molecule, while the two isoquinolines are joined in similar manner in all three compounds . The difference in structure between ecteinascidin and the jorumycin analog PM00104 could explain, at least partly, why these two drugs display slightly different DNA‐binding properties and nucleotide excision repair dependencies …”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

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Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.

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Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…) . Petek and Jones recently reviewed the preclinical and clinical data related to PM00104, which has entered several ongoing Phase II clinical trials.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

See 2 more Smart Citations

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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“…3 Zalypsis is one such molecule. It is a synthetic alkaloid related to substances isolated from marine organisms, 4 and has a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction. Interestingly, this activity is present in cells with a functional, as well as a mutated, p53.…”

Section: Introductionmentioning

confidence: 99%

Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone

et al. 2016

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Alkylating Agents and Platinum Antitumor Compounds

Siddik

2017

Holland‐Frei Cancer Medicine

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Overview Alkylating agents and platinum‐based compounds are highly potent antitumor drugs used in the treatment of a variety of cancers. These drugs target DNA (deoxyribonucleic acid) but require activation by spontaneous or metabolic transformation to induce formation of DNA monofunctional adducts and interstrand and intrastrand crosslinks. As a result of this damage, the DNA unwinds and/or bends, and such distortions are then recognized by specialized DNA damage recognition proteins to activate checkpoints, which arrest the cell cycle to allow cells time to repair the damage and survive. If the DNA damage is extensive and repair cannot be completed, then cells activate p53‐dependent or independent apoptosis (programmed cell death) to affect antitumor drug response. As activated species from alkylating agents and platinum compounds are not tumor‐selective, they will also interact with DNA and other endogenous macromolecules in normal cells to induce severe side effects; at times the toxicity can be irreversible and cumulative and, thereby, presents a dose‐limiting barrier. Another limitation is that genetic changes in tumors that are either intrinsic or acquired can inhibit apoptosis and induce resistance to alkylating and platinating drugs. Resistance mechanisms may be observed in the form of reduced drug accumulation, increased drug inactivation, increased DNA repair, failure of DNA damage recognition system to recognize the damage, and aberrant apoptotic signal transduction pathways. Rational strategies to circumvent resistance mechanisms are, therefore, needed desperately to enhance patient care.

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PM00104 (Zalypsis®): A Marine Derived Alkylating Agent

Cited by 29 publications

References 25 publications

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone

Alkylating Agents and Platinum Antitumor Compounds

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