Microtubule-associated proteins x PARP1

Last update 08 May 2025

Basic Info

Related Targets

Microtubule-associated proteinsPARP1

Drugs associated with Microtubule-associated proteins x PARP1

TP-3(China Pharmaceutical University)

Target

Microtubule-associated proteins x PARP1

Mechanism

Microtubule-associated proteins inhibitors [+1]

Active Org.

China Pharmaceutical University

Originator Org.-

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Microtubule-associated proteins x PARP1

100 Translational Medicine associated with Microtubule-associated proteins x PARP1

0 Patents (Medical) associated with Microtubule-associated proteins x PARP1

Literatures (Medical) associated with Microtubule-associated proteins x PARP1

01 Nov 2024·European Journal of Medicinal Chemistry

Discovery of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives as tubulin polymerization inhibitors for anticancer therapy: The in vitro and in vivo biological evaluation

Article

Author: Xu, Shiqiang ; Song, Wei ; Li, Ling ; He, Zhaolong ; Shi, Cai ; Yang, Jingxiang ; Yang, Boning ; Yang, Jian ; Song, Jian

A series of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives were designed, synthesized and estimated for their in vitro antiproliferative activities against HepG2, U251, PANC-1, A549 and A375 cell lines. Among them, compound 32 was the most promising candidate, and displayed strong broad-spectrum anticancer activity. The mechanism studies revealed that compound 32 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, and induced apoptosis by up-regulating the expression of cleaved PARP-1 and caspase-3. Furthermore, molecular docking analysis suggested that compound 32 well occupied the binding site of tubulin. In addition, compound 32 exhibited no significant activity against 30 different kinases respectively, indicating considerable selectivity. Moreover, compound 32 significantly inhibited the tumour growth of the HepG2 xenograft in a nude mouse model by oral gavage without apparent toxicity. These results demonstrated that some 2-substituted 2, 3- dihydroquinazolin-4(1H)-one derivatives bearing phenyl, biphenyl, naphthyl or indolyl side chain at C₂-position might be potentially novel antitumor agents as tubulin polymerization inhibitors.

01 Apr 2024·Anti-Cancer Agents in Medicinal Chemistry

Design and Synthesis of Aspirin-chalcone Mimic Conjugates as Potential Anticancer Agents

Article

Author: Srour, Aladdin M ; Mohamed-Ezzat, Reham A

Background:Extensive research has been conducted on aspirin, a widely recognized NSAID medication, regarding its potential as an anticancer agent. Studies have revealed its ability to trigger cell death in different types of cancer cells.Methods:A set of aspirin-chalcone mimic conjugates 5a-k and 6a-d utilizing the freshly prepared acid chloride of aspirin moiety has been designed and synthesized. To evaluate the newly developed compounds, the NCI 60- cell line panel was employed to assess their anti-proliferative properties. Subsequently, cell cycle analysis was conducted along with an examination of the compounds' impact on the levels of p53, Bax, Bcl-2, active caspase- 3, and their inhibition mechanism of tubulin polymerization.Results:Derivative 6c displayed the best anticancer activity among the tested series while 6d was the best against breast cancer MDA-MB-468, therefore both of them were selected for the 5-dose stage, however, targeting MDA-MB-468, PI-flow cytometry of compound 6d proved the triggered cell growth arrest at the G1/S phase avoiding the mitotic cycle in MDA-MB-468 cells. Similarly, the upregulation of oncogenic parameters such as caspase-3, p53, and Bax/Bcl-2, along with the inhibition of PARP-1 enzyme level, was observed with compound 6d. This compound also exhibited a significant ability to induce apoptosis and disrupt the intracellular microtubule network through a promising activity as a tubulin polymerization inhibitor with IC50 = 1.065 ± 0.024 ng/ml. Furthermore, to examine the manner in which compound 6d binds to the active pocket of the tubulin polymerization enzyme, a molecular docking study was conducted.Conclusion:The study indicated that compound 6d could be a powerful microtubule-destabilizing agent. Therefore, further research on 6d could be worthwhile.

01 Nov 2023·Acta pharmacologica Sinica

Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma.

Article

Author: Leich, Ellen ; Efferth, Thomas ; Boulos, Joelle C ; Klauck, Sabine M ; Rigano, Daniela ; Chatterjee, Manik ; Formisano, Carmen ; Omer, Ejlal A ; Shan, Le-Tian

The majority of blood malignancies is incurable and has unforeseeable remitting-relapsing paths in response to different treatments. Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, has gained increased attention as a chemotherapeutic agent. In this study, we investigated the effects of cynaropicrin against multiple myeloma (MM) cells in vitro and assessed its in vivo effectiveness in a xenograft tumor zebrafish model. We showed that cynaropicrin exerted potent cytotoxicity against a panel of nine MM cell lines and two leukemia cell lines with AMO1 being the most sensitive cell line (IC₅₀= 1.8 ± 0.3 µM). Cynaropicrin (0.8, 1.9, 3.6 µM) dose-dependently reduced c-Myc expression and transcriptional activity in AMO1 cells that was associated with significant downregulation of STAT3, AKT, and ERK1/2. Cell cycle analysis showed that cynaropicrin treatment arrested AMO1 cells in the G₂M phase along with an increase in the sub-G₀G₁ phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G₀G₁ phase, implying cell death. Using confocal microscopy, we revealed that cynaropicrin disrupted the microtubule network in U2OS cells stably expressing α-tubulin-GFP. Furthermore, we revealed that cynaropicrin promoted DNA damage in AMO1 cells leading to PAR polymer production by PARP1 hyperactivation, resulting in AIF translocation from the mitochondria to the nucleus and subsequently to a novel form of cell death, parthanatos. Finally, we demonstrated that cynaropicrin (5, 10 µM) significantly reduced tumor growth in a T-cell acute lymphoblastic leukemia (T-ALL) xenograft zebrafish model. Taken together, these results demonstrate that cynaropicrin causes potent inhibition of hematopoietic tumor cells in vitro and in vivo.

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