Oncotarget: The Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas eurekalert.org/pub_releas…
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👤︎ u/Oncotarget
📅︎ May 24 2021
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The cover for issue 8 of Oncotarget features Figure 6, "MDM2 can be targeted sarcoma cell lines independent of p53 status," by Desai, et al. oncotarget.com/article/27…
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👤︎ u/Oncotarget
📅︎ Apr 13 2021
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Gossypol has anti-cancer effects by dual-targeting MDM2 and VEGF in human breast cancer. breast-cancer-research.bi…
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👤︎ u/GioCapri
📅︎ Mar 19 2021
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TEAD–YAP Interaction Inhibitors and MDM2 Binders from DNA‐Encoded Indole‐Focused Ugi Peptidomimetics

A focused approach : A DNA‐encoded peptoid library was designed by the Ugi multicomponent reaction around indole structures that mimic the side chain of tryptophan. Applying this focused library to the challenging cancer targets MDM2 and hTEAD4 yielded compounds for inhibitor development. Compounds binding to hTEAD4 disrupted the hTEAD4–YAP interaction, and reduced expression of a gene under control of the TEAD–YAP transcription factor complex.

Abstract

DNA‐encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, or “hot spot”, regions of protein–protein interactions. A DNA‐encoded combinatorial peptoid library was designed based on the Ugi four‐component reaction by employing tryptophan‐mimetic indole side chains to probe the surface of target proteins. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide “hexT”, encoded by DNA sequences, and substituted by azide‐alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor‐relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD‐YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.

https://ift.tt/2MVAn2p

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📅︎ Jul 15 2020
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MDM2‐Associated Clusterization‐Triggered Emission and Apoptosis Induction Effectuated by a Theranostic Spiropolymer

A spiropolymer (P1a2b, see picture) demonstrates cluster‐triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti‐apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating non‐toxicity in non‐cancerous cells.

Abstract

Heteroatom‐containing spiropolymers were constructed in a facile manner by a catalyst‐free multicomponent spiropolymerization route. P1a2b as the most potent of these spiropolymers, demonstrates cluster‐triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti‐apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating a good biocompatibility and non‐toxicity in non‐cancerous cells. The combined results from solution and cell‐based cluster‐triggered emission studies, docking, protein expression experiments and cytotoxicity data strongly support the MDM2‐binding hypothesis and indicate a potential application as a fluorescent cancer marker as well as therapeutic for this spiropolymer.

https://ift.tt/2HjdliT

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📅︎ May 16 2020
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Anyone have experiences w MDM2 inhibitors (AMG232 for example) to restore p53 function ?

Hi All, I am a cancer researcher beginning to oversee a new study involving AMG232 which is a second generation MDM2 inhibitor. This is a fairly new compound and seems to have a lot of promise in helping the body restore it's natural p53 tumor suppressor pathway. This study will be in soft tissue sarcoma, but this pathway dis-regulation is seen extensively in osteosarcoma and breast cancer so will be studied in those cancers as well. Just wanted to see if anyone had any first hand experiences? Impressions ? Side effects ? thanks all for your time reading.

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📅︎ Jan 17 2019
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miR-1305 Inhibits The Progression Of Non-Small Cell Lung Cancer By Regulating MDM2 dovepress.com/mir-1305-in…
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📅︎ Nov 11 2019
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Inhibiting MDM2-p53 Interaction Suppresses Tumor Growth in Patient-Derived Non–Small Cell Lung Cancer Xenograft Models journals.lww.com/jto/Abst…
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📅︎ Jul 28 2015
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Co-expression of MDM2 and CDK4 in transformed human mesenchymal stem cells induces dedifferentiated liposarcoma potency biorxiv.org/lookup/conten…
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👤︎ u/sburgess86
📅︎ Apr 02 2018
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Bifurcation analysis and potential landscapes of the p53-Mdm2 module regulated by the co-activator programmed cell death 5 scitation.aip.org/content…
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📅︎ Nov 04 2015
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Natural product MDM2 inhibitors: anticancer activity and mechanisms of action.

Please send me this article..at the earliest..

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👤︎ u/seshankm
📅︎ Sep 28 2015
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Study sheds light on cancer-causing gene regulation, "instead of an on-off switch for MDM2, the team found what looks like a dimmer switch, suggesting a more complicated signaling pathway that is sensitive to a changing environment." physorg.com/news201179887…
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👤︎ u/emil10001
📅︎ Aug 16 2010
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Paper request: MDM2, MDMX and p53 in oncogenesis and cancer therapy, Nature Rev Cancer, Feb 2013

http://www.ncbi.nlm.nih.gov/pubmed/23303139 Thanks so much!

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👤︎ u/UR911
📅︎ Jul 06 2013
🚨︎ report
TEAD‐YAP interaction inhibitors and MDM2 binders from DNA‐encoded indole‐focused Ugi‐peptidomimetics

DNA‐encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, or “hot spot” regions of protein‐protein interactions. A DNA‐encoded combinatorial peptoid library was designed based on the Ugi four‐component reaction employing tryptophan‐mimetic indole side chains to probe target protein surface. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide “hexT”, encoded by DNA sequences and substituted by azide‐alkyne cycloaddition to yield a library of 8,112 molecules. Selection experiments on the tumor‐relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD‐YAP interaction inhibitors that perturbed expression of a gene under the control of these Hippo pathway effectors.

https://ift.tt/2MVAn2p

👍︎ 2
💬︎
📅︎ Jun 15 2020
🚨︎ report
MDM2‐Associated Clusterization‐Triggered Emission and Apoptosis Induction Effectuated by a Theranostic Spiropolymer

A spiropolymer (P1a2b, see picture) demonstrates cluster‐triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti‐apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating non‐toxicity in non‐cancerous cells.

Abstract

Heteroatom‐containing spiropolymers were constructed in a facile manner by a catalyst‐free multicomponent spiropolymerization route. P1a2b as the most potent of these spiropolymers, demonstrates cluster‐triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti‐apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating a good biocompatibility and non‐toxicity in non‐cancerous cells. The combined results from solution and cell‐based cluster‐triggered emission studies, docking, protein expression experiments and cytotoxicity data strongly support the MDM2‐binding hypothesis and indicate a potential application as a fluorescent cancer marker as well as therapeutic for this spiropolymer.

https://ift.tt/2HjdliT

👍︎ 2
💬︎
📅︎ Mar 06 2020
🚨︎ report

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