Discovery of Marinopyrrole A (Maritoclax) as a Selective Mcl-1 Antagonist that Overcomes ABT-737 Resistance by Binding to and Targeting Mcl-1 for Proteasomal Degradation

Doi, Kenichiro; Li, Rongshi; Sung, Shen Shu; Wu, Hongwei; Liu, Yan; Manieri, Wanda; Gowda, Raghavendra; Awwad, Andy; Dewey, Alden; Liu, Xin; Amin, Shantu; Cheng, Ching-Yuan; Qin, Yong; Schönbrunn, E.; Daughdrill, Gary W.; Loughran, Thomas P.; Sebti, Saı̈d M.; Wang, Hong Gang

doi:10.1074/jbc.m111.334532

Cited by 141 publications

(201 citation statements)

References 42 publications

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“…64,65,74 It was also found that marinopyrrole A may restore activity of the anticancer drug ABT-737 to resistant cancer cells. 75 As such, these atropisomeric natural products show promise for broad medicinal application, and studies as to this potential are ongoing.…”

Section: Marinopyrroles: Determination Of Enzymatically-imposed Atropmentioning

confidence: 99%

A twist of nature – the significance of atropisomers in biological systems

2015

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. (2015). A twist of nature-the significance of atropisomers in biological systems. Natural Product Reports: a journal of current development in bioorganic chemistry, 32 (11), 1562-1583. A twist of nature-the significance of atropisomers in biological systems AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized. AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized.

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Section: Marinopyrroles: Determination Of Enzymatically-imposed Atropmentioning

confidence: 99%

A twist of nature – the significance of atropisomers in biological systems

2015

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“…It was reported that this natural product derived from a species of marine streptomycetes (47) binds to MCL-1, but not BCL-X L , disrupts the MCL-1/BIM complex, and elicits apoptosis in leukemia/lymphoma cell lines that are MCL-1-dependent, but not BCL-2 or BCL-X L -dependent (48). These effects were associated with proteasomal degradation of MCL-1.…”

Section: Marinopyrrole a (Maritoclax)mentioning

confidence: 99%

BH3 Mimetics: Status of the Field and New Developments

Billard

2013

Molecular Cancer Therapeutics

192

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Targeting apoptosis is an attractive approach in cancer therapy. The BH3-only proteins of the BCL-2 family (having only the BCL-2 homology domain BH3) can trigger apoptosis by binding to the prosurvival members of this family and neutralizing their functional activity (sequestration of the proapoptotic Bcl-2 family members). The "BH3 mimetic" concept has prompted the development of small molecules capable of mimicking BH3-only proteins and thus inducing apoptosis. The prototype BH3 mimetic ABT-737 selectively targets the three prosurvival proteins BCL-X L , BCL-2, and BCL-W (but not MCL-1 or A1) and its oral derivative ABT-263 has proved promising in clinical trials. Some putative BH3 mimetics are also tested clinically while others are still being characterized. This article recapitulates the various known BH3 mimetics and presents the recent developments in the field. The latter include (i) the identification of molecular determinants responsible for the specific interactions between BH3 motifs and the binding grooves of prosurvival proteins and (ii) the characterization of new compounds and particularly BH3 mimetics that antagonize either selectively MCL-1 or BCL-2 or a broad range of prosurvival proteins. These data are critical advances toward the discovery of novel anticancer agents. Mol Cancer Ther; 12(9); 1691-700. Ó2013 AACR.

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“…Marinopyrrole A (Maritoclax) [73,74] MCL-1 Marinopyrrole A induces apoptosis in MCL-1-dependent but not BCL-2-and BCL-XL-dependent manners in leukemia and melanoma cells [73,74].…”

Section: Umi-77 [70]mentioning

confidence: 99%

BH3 mimetics: Their action and efficacy in cancer chemotherapy

Nakajima¹,

Tanaka²

2016

Integr Cancer Sci Therap

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Evading apoptosis is a hallmark of cancer, and anti-apoptotic BCL-2 family proteins are frequently highly expressed in cancers. In cancer cells, aberrant DNA replication invokes replication-associated DNA damage signaling in cancer cells; however, DNA damage-induced apoptotic signals are masked by such apoptosis evasion systems. Therefore, it is considered that targeting of apoptosis is efficient for cancer cell-selective therapeutic methods. BCL-2 family proteins are critical regulators of mitochondrion-mediated apoptosis, and 'BH3-only' subfamily proteins induce apoptosis by binding to anti-apoptotic BCL-2 family proteins via their BH3 domain. BH3 mimetics are small molecules that mimic BH3-proteins by binding to anti-apoptotic BCL-2 family proteins. To date, more than 20 compounds have been identified, and their effects in cancer therapy have been analyzed. In this review, their efficacy in cancer chemotherapy will be discussed.

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Discovery of Marinopyrrole A (Maritoclax) as a Selective Mcl-1 Antagonist that Overcomes ABT-737 Resistance by Binding to and Targeting Mcl-1 for Proteasomal Degradation

Cited by 141 publications

References 42 publications

A twist of nature – the significance of atropisomers in biological systems

A twist of nature – the significance of atropisomers in biological systems

BH3 Mimetics: Status of the Field and New Developments

BH3 mimetics: Their action and efficacy in cancer chemotherapy

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