Last update 01 Nov 2024

TRAIL x ADCY10

Last update 01 Nov 2024

Basic Info

Related Targets

TRAILADCY10

Drugs associated with TRAIL x ADCY10

CN113717289

Patent Mining

Target

ADCY10 x TRAIL

Mechanism-

Active Org.

East China University of Science & Technology

Originator Org.

East China University of Science & Technology

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TRAIL x ADCY10

100 Translational Medicine associated with TRAIL x ADCY10

0 Patents (Medical) associated with TRAIL x ADCY10

Literatures (Medical) associated with TRAIL x ADCY10

01 Feb 2022·Applied Microbiology and BiotechnologyQ3 · ENGINEERING & TECHNOLOGY

SAC-TRAIL, a novel anticancer fusion protein: expression, purification, and functional characterization

Q3 · ENGINEERING & TECHNOLOGY

Article

Author: Zhang, Jian ; Ren, Yuhong ; Wei, Dongzhi ; Dong, Wanyuan

Recombinant protein pharmaceutical agents have been widely used for cancer treatment. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has broad-spectrum antitumor activity, its clinical applications are limited because most tumor cells eventually develop resistance to TRAIL-induced apoptosis through various pathways. Prostate apoptosis response-4 (Par-4) selectively induces apoptosis in cancer cells after binding to the cell surface receptor, GRP78. In this study, TRAIL was fused with the core domain of Par-4 (SAC) to produce a novel recombinant fusion protein. To obtain solubly expressed fusion protein, a small ubiquitin-related modifier (SUMO) was added to the N-terminus of the target protein. Cytotoxicity assays showed that the purified fusion protein exhibited more significant antitumor activity on cancer cells than that by native TRAIL. The connection order and linker sequence of the fusion proteins were optimized. In vitro cytotoxicity assay showed that the SAC-TRAIL fusion protein, which contained a flexible linker (G₄S)₃, optimally inhibited the proliferation of cancer cells. Immunofluorescence assays demonstrated that SAC-TRAIL could efficiently and specifically bind to cancer cells. Additionally, circular dichroism assays showed that the secondary structure of the recombinant protein with a flexible linker (G₄S)₃ has both a lower α-helix and higher random coiling, which facilitates the specific binding of SAC-TRAIL to the receptor. Collectively, these results suggest that the novel recombinant fusion protein SAC-(G₄S)₃-TRAIL is a potential therapeutic agent for cancer. KEY POINTS: • Improved tumor growth suppression and apoptosis induction potency of SAC-TRAIL. • Enhanced targeting selectivity of SAC-TRAIL in cancer cells. • Lower α-helix and higher random coiling in SAC-TRAIL with flexible linker (G₄S)₃.

01 Feb 2009·Bioorganic & Medicinal ChemistryQ3 · MEDICINE

Death receptor 5 targeting activity-guided isolation of isoflavones from Millettia brandisiana and Ardisia colorata and evaluation of ability to induce TRAIL-mediated apoptosis

Q3 · MEDICINE

Article

Author: Thaworn Kowithayakorn ; Masami Ishibashi ; Takashi Koyano ; Toshiyuki Sakai ; Hiroyuki Kikuchi ; Takashi Ohtsuki

Death receptor 5 (DR5) is an apoptosis-inducing membrane receptor for TNF-related apoptosis-inducing ligand (TRAIL). On screening for compounds that enhance DR5 expression using a luciferase assay with DLD-1/SacI, we previously identified 4'-demethyltoxicarol isoflavone (1) isolated from the leaves of Millettia brandisiana. In this study, we revealed that 1 sensitized TRAIL-resistant human gastric adenocarcinoma (AGS) cells to TRAIL-induced apoptosis by up-regulating the expression of DR5. 1 induced DR5 expression at both the mRNA and protein level. A human recombinant DR5/Fc chimera remarkably inhibited 1-induced apoptosis. These results suggest that the enhancement of DR5 expression by 1 was critical to the cell death. Furthermore, a MeOH extract of the bark of Ardisia colorata markedly enhanced DR5 activity in this screening system. Bioassay-guided fractionation of A. colorata led to the isolation and identification of a new isoflavone, coloratanin A (3), together with ten known compounds. The chemical structure of the new compound was elucidated on the basis of a spectroscopic analysis.

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