Delving into the Latest Updates on Shikonin Suppository with Synapse

Overview

Basic Info

Drug Type

Herbal medicine

Synonyms-

Target-

Mechanism-

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Prostatitis

Originator Organization-

Active Organization-

Inactive Organization

Beijing Lingrui Weiya Technology Co. Ltd.Jilin Institute of Traditional Chinese Medicine

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor solubility of SKN and GFB limits their clinical application because of low bioavailability. Wheat germ agglutinin (WGA) can selectively bind to sialic acid and N-acetylglucosamine on the surfaces of microfold cells and enterocytes, and is a targeted biocompatible material. Therefore, we created a co-delivery micelle system called SKN/GFB@WGA-micelles with the intestinal targeting functions to enhance the oral absorption of SKN and GFB by promoting mucus penetration for nanoparticles via oral administration. In this study, Caco-2/HT29-MTX-E12 co-cultured cells were used to simulate a mucus/enterocyte dual-barrier environment, and HCC827/GR cells were used as a model of drug-resistant lung cancer. We aimed to evaluate the oral bioavailability and anti-tumor effect of SKN and GFB using the SKN/GFB@WGA-micelles system. In vitro and in vivo experimental results showed that WGA promoted the mucus penetration ability of micelles, significantly enhanced the uptake efficiency of enterocytes, improved the oral bioavailability of SKN and GFB, and exhibited good anti-tumor effects by reversing drug resistance. The SKN/GFB@WGA-micelles were stable in the gastrointestinal tract and provided a novel safe and effective drug delivery strategy.

01 Jan 2025·Current Medicinal Chemistry

Determination of Inhibitory Effect of PKM2 Enzyme and Antitumoral Activity of Novel Coumarin-naphthoquinone Hybrids

Article

Author: de Queiroz, Lucas Nicolau ; da Silva Magalhaes Forezi, Luana ; de Carvalho da Silva, Fernando ; Robbs, Bruno Kaufmann ; Rabelo, Vitor Won-Held ; de Souza, Acacio Silva ; Ribeiro, Amanda Vieira ; Pontes, Bruno ; Ouverney, Gabriel ; de Andrade Borges, Amanda ; de Almeida, Elan Cardozo Paes ; Ribeiro, Ruan Carlos Busquet ; Ferreira, Vitor ; Arruda, Afonso Thales Sousa ; Abreu, Paula Alvarez ; da Fonseca, Anna Carolina Carvalho

Background:Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science.Objective:This work presents the pioneering examples of naphthoquinone-coumarin hybrids as a new category of highly effective cytotoxic substances targeting oral squamous cell carcinoma (OSCC).Methods:Given the significance of both naphthoquinones and coumarins as essential pharmacophores/ privileged structures in the quest for anticancer compounds, this study focused on the synthesis and evaluation of novel naphthoquinones/coumarin hybrids against oral squamous cell carcinoma.Results:By several in vitro, in silico, and in vivo approaches, we demonstrated that compound 6e was highly cytotoxic against OSCC cells and several other cancer cell types and was more selective than current chemotherapeutic drugs (carboplatin) and the naphthoquinone lapachol. Furthermore, compound 6e was non-hemolytic and tolerated in vivo at 50 mg/kg with an LD50 of 62.5 mg/kg. Furthermore, compound 6e did not induce apoptosis and cell cycle arrest but led to intracellular vesicle formation with LC3 aggregation in autophagosomes, suggesting an autophagic cell death. Additionally, 6e had a high-affinity potential for PKM2 protein, higher than the known ligands, such as lapachol or shikonin, and was able to inhibit this enzyme activity in vitro.Conclusion:We assert that compound 6e shows promise as a potential lead for a novel chemotherapeutic drug targeting OSCC, with potential applicability to other cancer types.

01 Dec 2024·Molecular Biology Reports

Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulation

Article

Author: Liu, Jie ; Liang, Jing ; Ye, Xin ; Wang, Jun ; Xie, Qi ; Chen, Jinghua ; Wang, Xiumei ; Liu, Xiaolin ; Li, Yan

AbstractBackgroundPD-1 blockade has shown impressive clinical outcomes in colorectal cancers patients with high microsatellite instability (MSI-H). However, the majority of patients with colorectal cancer who present low microsatellite instability (MSI-L) or stable microsatellites (MSS) show little response to PD-1 blockade therapy. Here, we have demonstrated that Shikonin (SK) could induce cell death of CT26 cells via classically programmed and immunogenic pathways.Methods and resultsSK promoted the membrane exposure of calreticulin and upregulated the expression of heat shock protein 70 (Hsp70). The upregulation of Hsp70 was dependent on ROS induced by SK and silencing of PKM2 in CT26 cells reverts ROS upregulation. Besides, SK synergizes with PD-1 blockade in CT26 tumor mice model, with the increase of intramural DC cells and CD8+ T cells. The expression of Hsp70 in tumor tissue was also increased in combinational SK plus αPD-1 therapy group.ConclusionsOur study elucidated the potential role of ‘Shikonin-PKM2-ROS-Hsp70’ axis in the promotion of efficacy of PD-1 blockade in CRC treatments, providing a potential strategy and targets for improving the efficacy of PD-1 blockade in colorectal cancer.

100 Deals associated with Shikonin Suppository

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatitis	Phase 1	CN	Jilin Institute of Traditional Chinese Medicine	06 Sep 2008
Prostatitis	Phase 1	CN	Beijing Lingrui Weiya Technology Co. Ltd.	06 Sep 2008