Design, synthesis, and biological evaluation of estrone-derived hedgehog signaling inhibitors

Winkler, Jeffrey D.; Isaacs, André K.; Xiang, Chaomei; Baubet, Valérie; Dahmane, Nadia

doi:10.1016/j.tet.2011.10.028

Cited by 6 publications

(3 citation statements)

References 42 publications

(25 reference statements)

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“…Further, Winkler et al 119 have simplified the structure of analog 12g by systematic truncation of the steroidal framework. For this, compound 12h (Figure 12A) was synthesized, which lacks the a , b ring system present in analog 12g .…”

Section: Recent Advances In Design Of Hh Pathway Inhibitorsmentioning

confidence: 99%

Design of Hedgehog pathway inhibitors for cancer treatment

Bariwal

Kumar

Dong

et al. 2018

Medicinal Research Reviews

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Hedgehog (Hh) signaling is involved in the initiation and progression of various cancers and is essential for embryonic and postnatal development. This pathway remains in the quiescent state in adult tissues but gets activated upon inflammation and injuries. Inhibition of Hh signaling pathway using natural and synthetic compounds has provided an attractive approach for treating cancer and inflammatory diseases. While the majority of Hh pathway inhibitors target the transmembrane protein Smoothened (SMO), some small molecules that target the signaling cascade downstream of SMO are of particular interest. Substantial efforts are being made to develop new molecules targeting various components of the Hh signaling pathway. Here, we have discussed the discovery of small molecules as Hh inhibitors from the diverse chemical background. Also, some of the recently identified natural products have been included as a separate section. Extensive structure-activity relationship (SAR) of each chemical class is the focus of this review. Also, clinically advanced molecules are discussed from the last 5 to 7 years. Nanomedicine-based delivery approaches for Hh pathway inhibitors are also discussed concisely.

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Section: Recent Advances In Design Of Hh Pathway Inhibitorsmentioning

confidence: 99%

Design of Hedgehog pathway inhibitors for cancer treatment

Bariwal

Kumar

Dong

et al. 2018

Medicinal Research Reviews

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“…593 In ALS models of rodents, cholest-4-en-3one,oxime maintained 60% of neuromuscular junctions in gastrocnemius muscles, and inhibited muscular atrophy via inhibition of microglial activation. 596 Intriguingly, Reilly et al 597 showed that sonic hedgehog (Shh) and nerve growth factor (NGF) cooperate to generate basal forebrain cholinergic neurons, implying a possible use of the hedgehog pathway to fight neurodegeneration. are extremely toxic and particularly teratogenic due to the presence of steroidal alkaloids such as veratridine (CS 1.376) and cyclopamine (CS 1.377).…”

Section: Habitat and Descriptionmentioning

confidence: 99%

Alkaloids

Wiart

2014

Lead Compounds From Medicinal Plants for the Treatment of Neurodegenerative Diseases

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“…Recent studies have shown that activation of the Hh signaling pathway not only increases the risk of cancer patients, but also plays an important role in reducing the efficacy and tolerability of drugs [ 3 , 4 ]. At present, the inhibitor of Hh signaling pathway is mainly composed of the direct action of Smo [ 5 , 6 , 7 ], acting on the upstream of Smo [ 8 ], acting on the downstream of Smo [ 9 ], and other inhibitors, which are not very clear [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Smo Activity of Some Novel Benzamide Derivatives

et al. 2017

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Two series of benzamides compounds bearing piperidine groups were synthesized and the Gli-luc luciferase activity was screened by Gys-luc luciferase gene detection method. Compound 5q showed promising inhibition of hedgehog (Hh) signaling pathway. To further verify whether the Hh inhibitory activities of the target compounds are derived from their inhibition to the Smoothened (Smo) receptor, the compounds with good potency were evaluated in a fluorescence competitive displacement assays, the results showed the Smo inhibitory potency of these compounds correlated well with their Hh inhibition, which suggested that the observed Hh activity was driven by Smo inhibitors.

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Design, synthesis, and biological evaluation of estrone-derived hedgehog signaling inhibitors

Cited by 6 publications

References 42 publications

Design of Hedgehog pathway inhibitors for cancer treatment

Design of Hedgehog pathway inhibitors for cancer treatment

Alkaloids

Synthesis and Smo Activity of Some Novel Benzamide Derivatives

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