Increasing evidence points to the role of endogenous retroviruses (ERVs) in driving cancer cell proliferation. The purpose of this study was to explore the possibility of repurposing antiretroviral agents to inhibit ERVs as a new approach to cancer treatment. We found that an integrase strand-transfer inhibitor, dolutegravir (DTG), effectively inhibited the proliferation of multiple cancer cell lines and its antiproliferative potency was positively correlated with the expression levels of the human endogenous retrovirus type K (HERV-K). DTG inhibited the expression of HERV-K in multiple human cancer cell lines and the mouse mammary tumor virus (MMTV) in the murine 4T1 mammary cancer cell line. We chose the fast-growing BT-20 cell line as a model to study the in vitro antiproliferative mechanisms of DTG. BT-20 cells overexpressing both HERV-K env and pol genes became more resistant to DTG than cells transduced with vector alone. Knockdown of HERV-K also increased DTG resistance of BT-20 cells. The antiproliferative effect of DTG correlated with enhanced expression of E-cadherin and reduction in cell motility and invasiveness. Surprisingly, DTG stimulated expression of the env gene of MMTV in vivo and promoted metastasis of 4T1 tumor cells to the lungs. Taken together, our data support the role of ERVs in tumor development and encourage the further search for antiretroviral agents to treat malignancies in which ERVs are active.

20 Aug 2020·Anti-Cancer Agents in Medicinal ChemistryQ4 · MEDICINE

Synthesis, Biological and Computational Evaluation of Novel 2,3-dihydro-2-aryl-4-(4- isobutylphenyl)-1,5-benzothiazepine Derivatives as Anticancer and Anti-EGFR Tyrosine Kinase Agents

Q4 · MEDICINE

Article

Author: Prasad, Yejella R. ; Nissankararao, Srinath ; Shahanaaz, Shaik ; Shaik, Afzal B.

Background:Despite the availability of a variety of chemotherapeutic agents, cancer is still one of the leading causes of death worldwide because of the problems with existing chemotherapeutic agents like objectionable side effects, lack of selectivity, and resistance. Hence, there is an urgent need for the development of novel anticancer agents with high usefulness, fewer side effects, devoid of resistance and superior selectivity.Objective:The objective of this study is to synthesize a series of novel 1,5-benzothiazepine derivatives and evaluate their anticancer activity employing biological and computational methods.Methods:Twenty new benzothiazepines (BT1-BT20) were prepared by condensing different 1-(4- isobutylphenyl)ethanone chalcones with 2-amiothiophenol and evaluated for their anticancer activity by MTT assay against three cell lines including HT-29 (colon cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer). These compounds were also tested for their inhibitory action against EGFR (Epidermal Growth Factor Receptor) tyrosine kinase enzyme by taking into account of their excellent action against colon and breast cancer cell lines. Further, the structural features responsible for the activity were identified by Pharmacophorebased modelling using Schrodinger’s PHASETM software.Results:Among the 20 benzothiazepine derivatives, three compounds viz., BT18, BT19 and BT20 exhibited promising activity against the cell lines tested and the activity of BT20 was more than the standard methotrexate. Again the above three compounds showed excellent inhibitory activity with the percentage inhibition of 64.5, 57.3 and 55.8 respectively against EGFR (Epidermal Growth Factor Receptor) tyrosine kinase. PHASE identified a five-point AHHRR model for the proposed activity and the computational studies provided insights into the structural requirements for the anticancer activity and the results were consistent with the observed in vitro activity data.Conclusion:These novel benzothiazepines will be useful as lead molecules for the further development of new cancer therapies against colon and breast cancers.

01 Dec 2019·Biotechnology Reports

Green synthesis of silver nanoparticles at low temperature in a fast pace with unique DPPH radical scavenging and selective cytotoxicity against MCF-7 and BT-20 tumor cell lines

Article

Author: Zarepour, Atefeh ; Zarrabi, Ali ; Khorrami, Sadegh

"Black Peel Pomegranate" is a rare pomegranate cultivar that its specific features are still uncovered particularly in the bio-nano researches. The present study was organized to evaluate this pomegranate's potential in the biosynthesis of silver nanoparticles as well as bio-medical activities. According to the results, the pomegranate peel extract incredibly inhibited 100 % of DPPH free radicals (EC₅₀ = 5 μg/mL). This extract also induced more than 70 % cell death in the treated breast tumor cell lines, BT-20 and MCF-7. Interestingly, the extract was capable of biosynthesis very stable and small (15.6 nm) silver nanoparticles at ambient temperature in an ultra-fast pace. Likewise, these nanoparticles inhibited 77 % of DPPH free radicals (EC₅₀ = 9 μg/mL). Although this antioxidant capacity was lower than that of the extract, instead, the anticancer activity of the synthesized nanoparticles was significantly enhanced, so that they led to more than 81 % and 89 % cell death in the breast tumor cell lines BT-20 and MCF-7, respectively. Considerably, neither the extract nor the biosynthesized silver nanoparticles, showed significant toxicity against non-tumor cell lines (L-929) at the same concentrations. These features of the biosynthesized nanoparticles were quite outstanding in comparison with chemical/commercial ones. Overall, the present study introduces black peel pomegranate as a worthy bio-agent in the biosynthesis of silver nanoparticles with unique activities as well as a cancer treatment.

100 Deals associated with BT-20

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Preclinical	BE	Bone Therapeutics SA	17 Nov 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

BT-20

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation