Last update 01 Nov 2024

Top II x Tubulin

Last update 01 Nov 2024

Basic Info

Related Targets

Top IITubulin

Drugs associated with Top II x Tubulin

Entasobulin

Target

Top II x Tubulin

Mechanism

Top II inhibitors [+1]

Active Org.-

Originator Org.

AEterna Zentaris GmbH

Active Indication-

Inactive Indication

Lymphoma [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ICP-147

Target

Bacterial DNA gyrase x Top II x Tubulin

Mechanism

Bacterial DNA gyrase inhibitors [+2]

Active Org.-

Originator Org.

Atos SE

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MPI-6003

Target

Top II x Tubulin

Mechanism

Top II inhibitors [+1]

Active Org.-

Originator Org.

Matrix Pharmaceutical, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Top II x Tubulin

100 Translational Medicine associated with Top II x Tubulin

0 Patents (Medical) associated with Top II x Tubulin

Literatures (Medical) associated with Top II x Tubulin

01 Mar 2024·Experimental Eye Research

High Vasohibin-2 expression correlated with autophagy in proliferative diabetic retinopathy

Article

Author: Su, Na ; Ding, Yuzhi ; Qiu, Shanhu ; Luan, Jie ; Xu, Jian ; Sun, Zilin

Vasohibin-2 (VASH2) is confirmed to be associated with angiogenesis. To investigate the vitreous levels of VASH2 and how VASH2 induces angiogenesis in proliferative diabetic retinopathy (PDR), a total of 120 eyes were enrolled in this prospective and randomized controlled study and the vitreous level of VASH2 was quantified by Luminex liquid suspension chip. Vector systems were applied in human retinal microvascular endothelial cells (HRMECs) for VASH2 gene overexpression, along with interfering lentiviral vectors (VASH2-shRNA) for VASH2 gene silencing. Cell migration, autophagic flux, as well as the expression of α-tubulin, detyrosinated ⍺-tubulin, LC3 II/LC3 I, P62 were detected under normal, VASH2 overexpression, or interference conditions. The level of VASH2 in PDR patients was significantly higher (218.61 ± 30.14 pg/ml) than that in ERM/MH patients (80.78 ± 2.05 pg/ml) (P = 0.001). The migration ability of HRMECs was significantly increased in VASH2 overexpression group, while in the interfering group, the migration ability decreased. VASH2 increased the detyrosination of ⍺-tubulin. The high fluorescence intensity of autophagic flux showed an activation of autophagy in VASH2 overexpression group, which was also confirmed by the increase of LC3 II/LC3 I ratio and the decrease of P62. Collectively, the present study shows in PDR, vitreous level of VASH2 is higher. VASH2 promotes neovascularization by inducing autophagy, suggesting VASH2 could be a new anti-angiogenic drug target for PDR.

12 Dec 2023·Journal of Biomolecular Structure and Dynamics

Exploring the mechanism of action of podophyllotoxin derivatives through molecular docking, molecular dynamics simulation and MM/PBSA studies

Article

Author: Mulpuru, Viswajit ; Mishra, Nidhi ; Mishra, Anamika

The chemical structure of a compound directly affects its biological activity, as different functional groups can change a compound's activity. With this in mind, the current study aims to predict the likely mechanism of action of several podophyllotoxin derivatives whose biological activities have already been documented. The interactions of the derivatives of podophyllotoxin with tubulin (PDB ID: 6NNG) and topoisomerase II (PDB ID: 3QX3), the two recognised targets of podophyllotoxin, were examined using molecular docking experiments. According to the molecular docking result, tubulin, and the investigated variants of podophyllotoxin interact more effectively than topoisomerase. The greatest docking score of the compounds was -12.200 against tubulin and -4.511 against topoisomerase, indicating that tubulin is the target of these drugs. Further to ascertain the strength of the interaction between the best-docked derivatives and the target protein, additional molecular dynamics investigations were also incorporated. With tubulin, the derivatives engage steadily, while with topoisomerase, the ligands shift from the protein's initial binding site to its DNA binding site. MMPBSA analysis was used to examine the stability of their relationship.Communicated by Ramaswamy H. Sarma.

31 Dec 2022·Journal of Enzyme Inhibition and Medicinal ChemistryQ2 · MEDICINE

New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

Q2 · MEDICINE

ArticleOA

Author: Ebeid, Kareem ; Abuo-Rahma, Gamal El-Din A. ; Abd El-Hafeez, Amer Ali ; Ghosh, Pradipta ; Abourehab, Mohammed A. S. ; Mohammed, Hamada H. H. ; Alhaj-Suliman, Suhaila O. ; Mekkawy, Aml I. ; Wafa, Emad I. ; Hayallah, Alaa M. ; Salem, Aliasger K. ; Abbas, Samar H.

A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones 4a-j were synthesised as potential anticancer agents. Hybrids 4a-j exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds 4a-j displayed IC₅₀s ranged from 2.53-8.67 µM, 8.67-62.47 µM, and 4.19-24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC₅₀ values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC₅₀ values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC₅₀ = 1.22 µM). Also, hybrids 4a, 4b, 4e, 4i, and 4j exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.

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