Delving into the Latest Updates on Elemene with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target-

Mechanism-

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Dalianhualijingang Pharmaceutical Co. Ltd.

Active Organization

Dalianhualijingang Pharmaceutical Co. Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (01 Jan 1996),

Neoplasms

Regulation-

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Structure

Molecular FormulaC15H24

InChIKeyOPFTUNCRGUEPRZ-QLFBSQMISA-N

CAS Registry515-13-9

The goal of this phase II randomized clinical trial is to compare the safety and efficacy of Elemene plus Stupp Protocol (the new protocol) and Stupp Protocol alone (the standard protocol) in patients with newly-diagnosed glioblastomas (ndGBMs). The main questions to answer are:
Whether the new treatment protocol (Elemene plus Stupp Protocol) is clinically safe for ndGBM patients.
Whether the new treatment protocol (Elemene plus Stupp Protocol) brings better survival benefits for ndGBM patients compared to the standard-of-care Stupp Protocol.
Study participants will be enrolled in 5 hospitals in China and randomly assigned to receive either the new protocol or the standard protocol. The overall survival (OS) rate in the 12th month, the progression-free survival (PFS) rate in the 6th month, OS, PFS, and adverse events assessed by the CTCAE (Common Terminology Criteria for Adverse Events) will be evaluated for all patients.

Start Date01 May 2023

Sponsor / Collaborator

Peking Union Medical College Hospital

NCT04674527 / Unknown statusPhase 2IIT

A Pilot Study of Elemene Injectable Emulsion in Treating Patients With Refractory Glioblastoma

This is a pilot phase I study to evaluate the safety and efficacy on elemene injectable emulsion in treating patients with glioblastoma. Elemene, isolated from the Chinese medicinal herb Curcuma wenyujin, was shown to exhibit antitumor activity in human and murine tumor cells in vitro and in vivo.Elemene injectable emulsion against malignant tumors was low. Therefore, the effect of Elemene injectable emulsion being used in clinical settings needs to be confirmed by further RCTs.

Start Date01 Jun 2021

Sponsor / Collaborator

Second Affiliated Hospital Zhejiang University School of Medicine

[+1]

ITMCTR2000003761 / RecruitingNot ApplicableIIT

Clinical study of HIPEC combined with traditional Chinese medicine elemene in the treatment of advanced colorectal cancer

Start Date01 Sep 2020

Sponsor / Collaborator-

100 Clinical Results associated with Elemene

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100 Translational Medicine associated with Elemene

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100 Patents (Medical) associated with Elemene

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526

Literatures (Medical) associated with Elemene

01 Aug 2024·Current Pharmaceutical Design

Elemene Injection Overcomes Paclitaxel Resistance in Breast Cancer through AR/RUNX1 Signal: Network Pharmacology and Experimental Validation

Article

Author: Huang, Tianjian ; Yu, Jiangting ; Gu, Xidong ; Chen, Jiaying ; Fu, Yuanyuan ; Xie, Xiaohong ; Xu, Leilai ; Fan, Shuyao ; Sui, Xinbing

Background:Paclitaxel (PTX) is a cornerstone chemotherapy for Breast Cancer (BC), yet its impact is limited by emerging resistance. Elemene Injection (EI) has shown potential in overcoming chemotherapy resistance. However, the efficacy by which EI restores PTX sensitivity in BC and the implicated molecular mechanism remain uncharted.Methods:Network pharmacology and bioinformatic analysis were conducted to investigate the targets and mechanisms of EI in overcoming PTX resistance. A paclitaxel-resistant MCF-7 cell line (MCF-7PR) was established. The efficacy of EI and/or PTX in inhibiting cell viability was evaluated using sulforhodamine B assay, while cell proliferation was assessed using EdU staining. Furthermore, protein and gene expression analysis was performed through Western blotting and qPCR.Results:The EI containing three active components exhibited a multifaceted impact by targeting an extensive repertoire of 122 potential molecular targets. By intersecting with 761 differentially expressed genes, we successfully identified 9 genes that displayed a direct association with resistance to PTX in BC, presenting promising potential as therapeutic targets for the EI to effectively counteract PTX resistance. Enrichment analysis indicated a significant correlation between these identified targets and critical biological processes, particularly DNA damage response and cell cycle regulation. This correlation was further substantiated through meticulous analysis of single-cell datasets. Molecular docking analysis revealed robust binding affinities between the active components of the EI and the identified molecular targets. Subsequently, in vitro experiments unequivocally demonstrated the dose- and time-dependent inhibitory effects of the EI on both PTX-resistant and sensitive BC cell lines, effectively mitigating the resistance phenotype associated with PTX administration. Furthermore, our findings have indicated EI to effectively suppress the protein expression levels of AR and RUNX1 in MCF-7 and MCF-7PR cells under PTX treatment, as well as downregulate the mRNA expression levels of stem-like properties’ markers, KLF4 and OCT4, in these cell lines.Conclusion:Elemene Injection (EI) application has exhibited a significant capability to mitigate PTX resistance in BC, which has been achieved through targeted suppression of the AR/RUNX1 axis, revealing a key strategy to overcome chemotherapeutic resistance.

01 Aug 2024·Journal of Advanced Research

β-Elemene induced ferroptosis via TFEB-mediated GPX4 degradation in EGFR wide-type non-small cell lung cancer

Article

Author: Zhao, Li-Ping ; Hu, Die ; Wang, Hao-Jie ; Lou, Jian-Shu ; Hu, Jun-Hu ; Tang, Xiao-Qi ; Guan, Zheng-Rong ; Zhou, Zhao-Huang ; Jiang, Ya-Ping ; Xie, Tian ; Yu, Li-Hua

INTRODUCTIONβ-Elemene (β-ELE), derived from Curcuma wenyujin, has anticancer effect on non-small cell lung cancer (NSCLC). However, the potential target and detail mechanism were still not clear. TFEB is the master regulator of lysosome biogenesis. Ferroptosis, a promising strategy for cancer therapy could be triggered via suppression on glutathione peroxidase 4 (GPX4). Weather TFEB-mediated lysosome degradation contributes to GPX4 decline and how β-ELE modulates on this process are not clear.OBJECTIVESTo observe the action of β-ELE on TFEB, and the role of TFEB-mediated GPX4 degradation in β-ELE induced ferroptosis.METHODSSurface plasmon resonance (SPR) and molecular docking were applied to observe the binding affinity of β-ELE on TFEB. Activation of TFEB and lysosome were observed by immunofluorescence, western blot, flow cytometry and qPCR. Ferroptosis induced by β-ELE was observed via lipid ROS, a labile iron pool (LIP) assay and western blot. A549^{TFEB KO} cells were established via CRISPR/Cas9. The regulation of TFEB on GPX4 and ferroptosis was observed in β-ELE treated A549^WT and A549^{TFEB KO} cells, which was further studied in orthotopic NOD/SCID mouse model.RESULTSβ-ELE can bind to TFEB, notably activate TFEB, lysosome and transcriptional increase on downstream gene GLA, MCOLN1, SLC26A11 involved in lysosome activity in EGFR wild-type NSCLC cells. β-ELE increased GPX4 ubiquitination and lysosomal localization, with the increase on lysosome degradation of GPX4. Furthermore, β-ELE induced ferroptosis, which could be promoted by TFEB overexpression or compromised by TFEB knockout. Genetic knockout or inactivation of TFEB compromised β-ELE induced lysosome degradation of GPX4, which was further demonstrated in orthotopic NSCLC NOD/SCID mice model.CONCLUSIONThis study firstly demonstrated that TFEB promoted GPX4 lysosome degradation contributes to β-ELE induced ferroptosis in EGFR wild-type NSCLC, which gives a clue that TFEB mediated GPX4 degradation would be a novel strategy for ferroptosis induction and NSCLC therapy.

01 Aug 2024·World Journal of Microbiology and Biotechnology

Recent advances in lycopene and germacrene a biosynthesis and their role as antineoplastic drugs

Review

Author: Fordjour, Eric ; Liu, Chun-Li ; Yang, Yankun ; Bai, Zhonghu

Sesquiterpenes and tetraterpenes are classes of plant-derived natural products with antineoplastic effects. While plant extraction of the sesquiterpene, germacrene A, and the tetraterpene, lycopene suffers supply chain deficits and poor yields, chemical synthesis has difficulties in separating stereoisomers. This review highlights cutting-edge developments in producing germacrene A and lycopene from microbial cell factories. We then summarize the antineoplastic properties of β-elemene (a thermal product from germacrene A), sesquiterpene lactones (metabolic products from germacrene A), and lycopene. We also elaborate on strategies to optimize microbial-based germacrene A and lycopene production.

100 Deals associated with Elemene

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Neoplasms	CN	Dalianhualijingang Pharmaceutical Co. Ltd.	01 Jan 1996

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CSCO2022	Not Applicable	Malignant ascites	42	榄香烯乳状注射液	xzraebwjpu(smacaqhrpr) = odrdnhwwra uyxfnrilmr (gjsjwvgjpt )	Positive	21 Sep 2022
CSCO2021	Not Applicable	HER2 negative Gastric Cancer	66	榄香烯口服乳+奥沙利铂+替吉奥	(qmhsmjcjcc) = rsohvyzdcq mldkeyjtdg (ocwqjdwenb ) View more	Positive	25 Sep 2021
				奥沙利铂+替吉奥	(qmhsmjcjcc) = sriifrxaue mldkeyjtdg (ocwqjdwenb ) View more
CSCO2021	Not Applicable	-	65	榄香烯注射液联合TMZ(替莫唑胺)	ivebizqvtc(ovjyxaxsha) = bgrmpodsih ngvqvowygb (jfzvybfhvo )	Positive	25 Sep 2021
				单TMZ组	ivebizqvtc(ovjyxaxsha) = vshrghdhcf ngvqvowygb (jfzvybfhvo )
CSCO2021	Not Applicable	Esophageal Carcinoma	50	榄香烯 (单放组)	vzazwoeswi(cytwgsykos) = jukznohtdd wvdywdrasi (ctohartnun ) View more	-	25 Sep 2021
				榄香烯 (综合组)	vzazwoeswi(cytwgsykos) = dcrctqxsok wvdywdrasi (ctohartnun ) View more
CSCO2021	Not Applicable	Liver Cancer	60	榄香烯注射液联合放疗	idaeasjjwu(jexxcyruvl) = hkldxumfhb lfhgglopsz (vyiseifvot ) View more	Positive	25 Sep 2021
				榄香烯注射液 (单纯放疗)	idaeasjjwu(jexxcyruvl) = gdcncrxxov lfhgglopsz (vyiseifvot )
CSCO2020	Not Applicable	Malignant ascites	42	腹腔灌注榄香烯注射液	exvqztouhx(nmrvyuwlvw) = qyekkengfh tjgukcxjuk (pboaxskini )	Positive	19 Sep 2020
CSCO2020	Not Applicable	Hypopharyngeal Carcinoma	56	榄香烯口服乳	fecwgwolhf(afcmeymldq) = rysojuladf qvksrdbisn (crkryxvpwx ) View more	Positive	19 Sep 2020
				同步放化疗	fecwgwolhf(afcmeymldq) = epiwfxcesz qvksrdbisn (crkryxvpwx ) View more
CSCO2020	Not Applicable	Non-Small Cell Lung Cancer \| Brain metastases	90	榄香烯注射液联合全脑放疗	dygdsaosgu(qiibbxhnlt) = iyhoqsznwr jedspqvzhf (ztbiwcxlpo ) View more	-	19 Sep 2020
				榄香烯注射液 (全脑放疗)	dygdsaosgu(qiibbxhnlt) = bozawtrqxy jedspqvzhf (ztbiwcxlpo ) View more
CSCO2020	Not Applicable	Liver Cancer	60	榄香烯注射液联合介入化疗	gmfdgtrsos(ippwtkaqfl) = 榄香烯组明显减轻，两组比较差异有统计学意义(P<0.05) iccdookvyi (xllazudind ) View more	-	19 Sep 2020
				榄香烯注射液 (介入化疗)
CSCO2020	Not Applicable	Advanced gastric carcinoma	50	榄香烯口服乳	(walqzesvtk) = rddkzzsmwx wtdwdtbgqd (tjpxgnjitx ) View more	Positive	19 Sep 2020
				榄香烯 (最佳支持治疗)	(walqzesvtk) = sziprgedls wtdwdtbgqd (tjpxgnjitx )