Targeting prostate cancer with compounds possessing dual activity as androgen receptor antagonists and HDAC6 inhibitors

Jadhavar, Pradeep S.; Ramachandran, Sreekanth; Riquelme, Eduardo; Gupta, Ashu; Quinn, Kevin P.; Shivakumar, Devleena; Ray, Soumya S.; Zende, Dnyaneshwar; Nayak, Anjan K.; Miglani, Sandeep K.; Sathe, Balaji D.; Raja, Mohd.; Farias, Olivia; Belmar, Sebastián; Guerrero, Julien; Bernales, Sebastián; Chakravarty, Sarvajit; Hung, David T.; Lindquist, Jeffrey N.; Rai, Roopa

doi:10.1016/j.bmcl.2016.09.058

Cited by 16 publications

(9 citation statements)

References 30 publications

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“…Moreover, the expression of E-cadherin is decreased, while the levels of several mesenchymal markers including vimentin, Twist, ZEB1, ZEB2, and Slug are upregulated [109]. More importantly, multiple agents have been confirmed to exert their anticancer effects by inactivating and downregulating HDAC6 in PrCa cells [110][111][112][113]. It has been noted that SPOP specifically interacts with HDAC6 and promotes its polyubiquitination and degradation in human 293 T cells [30].…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

The emerging role of SPOP protein in tumorigenesis and cancer therapy

Song

Pan

et al. 2020

Mol Cancer

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The nuclear speckle-type pox virus and zinc finger (POZ) protein (SPOP), a representative substrate-recognition subunit of the cullin-RING E3 ligase, has been characterized to play a dual role in tumorigenesis and cancer progression. Numerous studies have determined that SPOP suppresses tumorigenesis in a variety of human malignancies such as prostate, lung, colon, gastric, and liver cancers. However, several studies revealed that SPOP exhibited oncogenic function in kidney cancer, suggesting that SPOP could exert its biological function in a cancer type-specific manner. The role of SPOP in thyroid, cervical, ovarian, bone and neurologic cancers has yet to be determined. In this review article, we describe the structure and regulation of SPOP in human cancer. Moreover, we highlight the critical role of SPOP in tumorigenesis based on three major categories: physiological evidence (animal models), pathological evidence (human cancer specimens) and biochemical evidence (downstream ubiquitin substrates). Furthermore, we note that SPOP could be a promising therapeutic target for cancer treatment.

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Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

The emerging role of SPOP protein in tumorigenesis and cancer therapy

Song

Pan

et al. 2020

Mol Cancer

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“…Of interest, hybrid 95 was 10‐fold less toxic than the parent SAHA on the VERO normal cell lines with IC 50 of 11 μM compared to 1.5 μM of the toxic parent SAHA rendering this conjugate promising start for further SAR study using other linkers and ZBGs. Additionally, In 2016, Jadhavar et al . reported dual AR/HDAC inhibitors 97 and 98 by attaching the aliphatic linker and zinc binder to enzalutamide ( 96 ) on the amide position on the ring C through either amide bond in 97 or ester bond in 98 (Figure ).…”

Section: Design Of Dual Hdac/nuclear Receptors Targeting Agentsmentioning

confidence: 99%

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

Hesham

Lasheen

Abouzid

2018

Medicinal Research Reviews

122

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Recently, molecular hybridization paradigm became an interesting and smart way to defeat the multifaceted cancer disease by a single molecular entity that acts via several mechanisms just like a magic bullet. Also, HDAC is an important epigenetic target in drug discovery, and the HDAC inhibitors showed successful pattern as cytotoxic agents. Because of their flexible structure activity relationship, it was easy to link them to other anticancer scaffolds. So, many dual action HDAC inhibitors have been developed and most of these hybrids have higher potency than the constituting parents in fighting of the cancer cells. This review describes potential applications of chimeric HDAC inhibitors, which simultaneously modulate not only HDAC but also multiple targets, in treatment of relapsing and drug-resistant cancers. We have nearly collected most of the reported dual action HDAC inhibitors yet to provide a comprehensive guide for the drug discovery process for developing more efficient anticancer agents.

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“…Several examples in these therapies include HDACIs with topoisomerase inhibitors, antiestrogens, antiandrogens, LSD inhibitors, tubulin inhibitors, VEGFR-2 inhibitors, EGFR/HER2 kinase inhibitors, JAK-2 inhibitors, Bcl-2 inhibitors, BRaf V600E inhibitors, and DNMT inhibitors 88-100. [149][150][151][152][153][154][155][156][157][158][159][160][161]…”

Section: Multi-targeted Hdacismentioning

confidence: 99%

Recent Prospectives of Anticancer Histone Deacetylase Inhibitors

Abbass

Hassan

Mohamed

et al. 2019

Journal of advanced Biomedical and Pharmaceutical Sciences

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Histone deacetylases (HDACs) are common targets for cancer therapy as they are expressed in many forms of cancers; several research studies have been introduced discussing the design of small molecules that target this abnormal epigenetic changes developed by HDACs in chromatin. In the past 10 years, HDAC inhibitors have emerged as important agents of interest in clinical trials for several types of cancers and other diseases. Due to the recent availability of a number of HDACIs into the market as effective anticancer agents (like vorinostat, belinostat, panobinostat, romidepsin, chidamide and pracinostat), HDACIs are considered one of the promising targeted anticancer agents. The current review highlights the most recent chemical modifications of HDACIs including different caps, linkers and zinc binding groups and interestingly the dual acting or multi-targeted HDACIs.

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Targeting prostate cancer with compounds possessing dual activity as androgen receptor antagonists and HDAC6 inhibitors

Cited by 16 publications

References 30 publications

The emerging role of SPOP protein in tumorigenesis and cancer therapy

The emerging role of SPOP protein in tumorigenesis and cancer therapy

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

Recent Prospectives of Anticancer Histone Deacetylase Inhibitors

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