Natural Products with Calmodulin Inhibitor Properties

Martínez-Luis, Sergio; Pérez-Vásquez, Araceli; Mata, Rachel

doi:10.1002/chin.200744230

Cited by 12 publications

(23 citation statements)

References 1 publication

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“…As found for CBP501, CMZ enhanced the cytotoxicity of cisplatin or bleomycin (EC 50 for CMZ around 5 mmol/L), but not that of DOX. Other CaM inhibitors W-7 and W-12 (24) show similar but weaker activity compared with CBP501. The affinity of CBP501 to CaM shown by SPR analysis is 10-fold higher than that of CBP501 to 14-3-3z.…”

Section: Discussionmentioning

confidence: 95%

CBP501-Calmodulin Binding Contributes to Sensitizing Tumor Cells to Cisplatin and Bleomycin

Mine

Yamamoto

Saito

et al. 2011

Molecular Cancer Therapeutics

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CBP501 is an anticancer drug currently in randomized phase II clinical trials for patients with non-small cell lung cancer and malignant pleural mesothelioma. CBP501 was originally described as a unique G 2 checkpoint-directed agent that binds to 14-3-3, inhibiting the actions of Chk1, Chk2, mitogen-activated protein kinase-activated protein kinase 2, and C-Tak1. However, unlike a G 2 checkpoint inhibitor, CBP501 clearly enhances the accumulation of tumor cells at G 2 -M phase that is induced by cisplatin or bleomycin at low doses and short exposure. By contrast, CBP501 does not similarly affect the accumulation of tumor cells at G 2 -M that is induced by radiation, doxorubicin, or 5-fluorouracil treatment. Our recent findings point to an additional mechanism of action for CBP501. The enhanced accumulation of tumor cells at G 2 -M upon combined treatment with cisplatin and CBP501 results from an increase in intracellular platinum concentrations, which leads to increased binding of platinum to DNA. The observed CBP501-enhanced platinum accumulation is negated in the presence of excess Ca 2þ . Some calmodulin inhibitors behave similarly to, although less potently than, CBP501. Furthermore, analysis by surface plasmon resonance reveals a direct, high-affinity molecular interaction between CBP501 and CaM (K d ¼ 4.62 Â 10 À8 mol/L) that is reversed by Ca 2þ , whereas the K d for the complex between CBP501 and 14-3-3 is approximately 10-fold weaker and is Ca 2þ independent. We conclude that CaM inhibition contributes to CBP501 0 s activity in sensitizing cancer cells to cisplatin or bleomycin. This article presents an additional mechanism of action which might explain the clinical activity of the CBP501-cisplatin combination.

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Section: Discussionmentioning

confidence: 95%

CBP501-Calmodulin Binding Contributes to Sensitizing Tumor Cells to Cisplatin and Bleomycin

Mine

Yamamoto

Saito

et al. 2011

Molecular Cancer Therapeutics

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“…A number of CaM antagonists have been described (for reviews, see [36,37]) and the CaM antagonist calmidazolium has previously been . NSC647889 has a mechanism of action similar to that of calmodulin inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Massive induction of apoptosis of multicellular tumor spheroids by a novel compound with a calmodulin inhibitor-like mechanism

Mohanty¹,

Fayad²,

Olofsson³

et al. 2013

J Cancer Ther Res

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“…Reinvestigation of the extract from the mycelium and culture medium of M. aurantiaca led to the isolation of Interaction of the alkaloid malbrancheamide with calmodulin 381 isomalbrancheamide B (3) [(5aS,12aS,13aS)-9-chloro-12,12-dimethyl-2,3,11,12,12a,13-hexahydro-1H,6H 5a,13a-(epiminomethano) indolizino [7,6b]carbazol-14-one (3)], along with the known compounds malbrancheamide (1), malbrancheamide B (2), and premalbrancheamide (4) (Figure 1) 13,20 . Compound 4 was recently detected in the fungus culture by Ding et al 21 while studying the biosynthesis of 1 and 2.…”

Section: Resultsmentioning

confidence: 99%

Fluorescence, circular dichroism, NMR, and docking studies of the interaction of the alkaloid malbrancheamide with calmodulin

Figueroa

González-Andrade

Sosa‐Peinado

et al. 2010

Journal of Enzyme Inhibition and Medicinal Chemistry

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Natural Products with Calmodulin Inhibitor Properties

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 12 publications

References 1 publication

CBP501-Calmodulin Binding Contributes to Sensitizing Tumor Cells to Cisplatin and Bleomycin

CBP501-Calmodulin Binding Contributes to Sensitizing Tumor Cells to Cisplatin and Bleomycin

Massive induction of apoptosis of multicellular tumor spheroids by a novel compound with a calmodulin inhibitor-like mechanism

Fluorescence, circular dichroism, NMR, and docking studies of the interaction of the alkaloid malbrancheamide with calmodulin

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