A Phase 1b Open-Label, Dose-Escalation, Safety, and Pharmacodynamic Study of Minnelide™ Capsules Given in Combination With Osimertinib in Patients With EGFR Mutated NSCLC

This phase Ib trial tests the side effects and best dose of minnelide when given together with osimertinib for the treatment of non-small cell lung cancer that has spread to other places in the body (advanced) and has a change (mutation) in a gene called EGFR. Minnelide is a biologically inactive compound that can be broken down in the body to produce a drug that rapidly releases the active compound triptolide when exposed to phosphatases in the bloodstream. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Minnelide and osimertinib may work better in treating patients with EGFR mutant advanced non-small cell lung cancer.

Start Date07 Mar 2022

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

ChiCTR2000036398 / RecruitingNot ApplicableIIT

Precise clinical research on the topical treatment of plaque psoriasis with triptolide

Start Date01 Oct 2020

Sponsor / Collaborator-

NCT03403569 / CompletedPhase 3IIT

Impact of Triptolide Wilfordii on Viral Suppression, Immune Recovery and Immune Activation Biomarkers in Treatment-naive HIV-1 Infection: a Randomized, Double-blinded, Placebo-controlled Study

The traditional Chinese herbal medicine Triptolide Wilfordii has displayed remarkable effect on the treatment of autoimmune diseases such as rheumatoid arthritis. Now that immunosuppression therapy has recently become a new strategy for HIV infection, it's reasonable to expect the anti-inflammatory effect of Triptolide Wilfordii in HIV infected patients. So we designed a randomized, double-blinded, placebo-controlled study to explore the efficacy and safety of Triptolide Wilfordii in new-onset HIV infection.

Start Date01 Sep 2018

Sponsor / Collaborator

Peking Union Medical College Hospital

100 Clinical Results associated with Triptolide

100 Translational Medicine associated with Triptolide

100 Patents (Medical) associated with Triptolide

1,616

Literatures (Medical) associated with Triptolide

31 Dec 2024·Scandinavian cardiovascular journal : SCJ

Molecular mechanism of triptolide in myocardial fibrosis through the Wnt/β-catenin signaling pathway

Article

Author: Zhang, Yiwen ; Lu, Feng

Objective. Myocardial fibrosis (MF) is a common manifestation of end-stage cardiovascular diseases. Triptolide (TP) provides protection against cardiovascular diseases. This study was to explore the functional mechanism of TP in MF rats via the Wnt/β-catenin pathway. Methods. The MF rat model was established via subcutaneous injection of isoproterenol (ISO) and treated with low/medium/high doses of TP (L-TP/M-TP/H-TP) or Wnt agonist BML-284. Cardiac function was examined by echocardiography. Pathological changes of myocardial tissues were observed by HE and Masson staining. Col-I/Col-III/Vimentin/α-SMA levels were detected by immunohistochemistry, RT-qPCR, and Western blot. Collagen volume fraction content was measured. Expression levels of the Wnt/β-catenin pathway-related proteins (β-catenin/c-myc/Cyclin D1) were detected by Western blot. Rat cardiac fibroblasts were utilized for in vitro validation experiments. Results. MF rats had enlarged left ventricle, decreased systolic and diastolic function and cardiac dysfunction, elevated collagen fiber distribution, collagen volume fraction and hydroxyproline content. Levels of Col-I/Col-III/Vimentin/α-SMA, and protein levels of β-catenin/c-myc/Cyclin D1 were increased in MF rats. The Wnt/β-catenin pathway was activated in the myocardial tissues of MF rats. TP treatment alleviated impairments of cardiac function and myocardial tissuepathological injury, decreased collagen fibers, collagen volume fraction, Col-I, Col-III, α-SMA and Vimentin levels, HYP content, inhibited Wnt/β-catenin pathway, with H-TP showing the most significant effects. Wnt agonist BML-284 antagonized the inhibitive effect of TP on MF. TP inhibited the Wnt/β-catenin pathway to repress the proliferation and differentiation of mouse cardiac fibroblasts in vitro. Conclusions. TP was found to ameliorate ISO-induced MF in rats by inhibiting the Wnt/β-catenin pathway.

01 Feb 2024·Inflammation

HSP90 Exacerbates Bone Destruction in Rheumatoid Arthritis by Activating TRAF6/NFATc1 Signaling

Article

Author: Guo, Wanyi ; Tao, Xueying ; Tian, Yage ; Wang, Qian ; Su, Xiaohui ; Lin, Na ; Liu, Liling ; Kong, Xiangying

Rheumatoid arthritis (RA) is an autoimmune disease characterized by a notably high disability rate, primarily attributed to cartilage and bone degradation. The involvement of heat shock protein 90 (HSP90) as a molecular chaperone in the inflammatory response of RA has been established, but its role in bone destruction remains uncertain. In the present study, the expression of HSP90 was augmented in osteoclasts induced by the receptor activator of nuclear factor-κB ligand. Additionaly, it was observed that the outcomes revealed a noteworthy inhibition of osteoclast formation and differentation when triptolide was utilized to hinder the expression of HSP90. Furthermore, the positive influence of HSP90 in osteoclast differentiation was substantiated by overexpressing HSP90 in osteoclast precursor cells. Mechanically, HSP90 significantly activated the TNF receptor-associated factor 6 (TRAF6)/Nuclear factor of activated T cells 1 (NFATc1) signaling axis, accompanied by markedly promoting osteoclast differentiation. This effect was consistently observed in the destructive joint of rats with collagen-induced arthritis, where HSP90 effectively activated osteoclasts and contributed to arthritic bone destruction by activating the TRAF6/NFATc1 signaling. Overall, the findings of this study provide compelling evidence that HSP90 exacerbates bone destruction in RA by promoting osteoclast differentiation through the activation of TRAF6/NFATc1 signaling, and interference with HSP90 may be a promising strategy for the discovery of anti-arthritic bone destruction agents.

25 Jan 2024·Journal of medicinal chemistryQ1 · MEDICINE

Selective Antitumor Effect and Lower Toxicity of Mitochondrion-Targeting Derivatization of Triptolide

Q1 · MEDICINE

Article

Author: Liu, Guoliang ; Lou, Hongxiang ; Xing, Wenlan ; Zhang, Yue ; Fan, Peihong ; Zhang, Tao

Triptolide has a significant antitumor activity, but its toxicity limits its clinical application. As the mitochondrion-targeting strategy showed an advantage in selective antitumor effect based on the higher mitochondrial membrane potential (MMP) in tumor cells than normal cells, the lipophilic cations triphenylphosphonium and E-4-(1H-indol-3-yl vinyl)-N-methylpyridinium iodide (F16) were selected as targeting carriers for structural modification of triptolide. The derivatives bearing F16 generally retained most antitumor activities, overcame its inhibition plateau phenomena, and enhanced its selective antitumor effect in lung cancer. The representative derivative F9 could accumulate in the mitochondria of NCI-H1975 cells, inducing apoptosis and a dose-dependent increase in intracellular reactive oxygen species and reducing MMP. Moreover, no effects were observed in normal cells BEAS-2B. In vivo studies showed that the developmental, renal, and liver toxicities of F9 to zebrafish were significantly lower than those of triptolide. This study provides a promising idea to relieve the toxicity problem of triptolide.

News (Medical) associated with Triptolide

17 Oct 2023

·www.biospace.com

Research in the Special Issue of Journal of Pharmaceutical Analysis Uncovers Previously Unexplored Cellular Mechanisms

XI'AN, China, Oct. 17, 2023 /PRNewswire/ -- Single-cell and spatially resolved omics have helped scientists take a closer look at tissue composition, structure, and function. This comprehensive understanding paves the way for them to uncover some intricate and previously unknown disease mechanisms. Three articles in the most recent special issue of the Journal of Pharmaceutical Analysis (JPA) discuss how single-cell and spatially resolved omics help unravel intercellular dynamics, aiding the development of novel therapeutic modalities. The first study focuses on microglia-astrocyte communication which may improve the therapeutic landscape of intracerebral hemorrhage (ICH). It is based on the notion that after a spinal cord injury or stroke, reactive astrocytes in the brain form a 'glial scar', that is lesser known in the context of ICH. To this end, the authors used spatial transcriptomics to investigate how microglial depletion (induced using PLX3397) affects astrocytic scar formation in the early and late stages of ICH. The article was available online in February 2023 and published in Volume 13, Issue 8 of JPA in August 2023. The researchers discovered that during early ICH, microglia-derived insulin-like growth factor 1 (IGF1) regulated protective astrocytic scar formation by activating the mechanistic target of rapamycin (mTOR) signaling pathway, which was further activated by the repopulating microglia. In chronic ICH, however, the scar had less protective and more neurotoxic effects. Interestingly, this effect could be partially reversed by delayed microglial depletion. The corresponding author Jianmin Zhang says, "Delayed microglial depletion may help with chronic ICH. Combined early-stage IGF1/osteopontin and late-stage PLX3397 treatment could be a promising therapeutic strategy for ICH." The second study attempted to investigate the testicular toxicity of triptolide, an active component of the traditional Chinese medicine Tripterygium wilfordii Hook. F., at the single cell level. Although triptolide is effective in the treatment of inflammatory diseases, its side effects, particularly testicular toxicity, limit its clinical use. The researchers used triptolide to treat mice, then isolated their testes and prepared single-cell suspensions. These were used to create a transcriptome map, which revealed that in treated mice, inflammatory response and reactive oxygen species signaling were upregulated, while germ cell and spermatid development were downregulated, indicative of triptolide-induced toxicity. "Our findings provide an invaluable resource for identifying the therapeutic targets of triptolide-induced male reproductive toxicity", explains corresponding author Dr. Chuanbin Yang. The third study elaborated on the single-cell and spatial analysis of epicardial cells in mouse heart tissue from embryonic day 9.5 to postnatal day 9. The team identified that the gene markers Msln, C3, Efemp1, and Upk3b were specific to postnatal (mature) epicardial tissue and were associated with increased extracellular matrix (ECM) signaling. Furthermore, while Wt1, Tbx18, and Upk3b were expressed at all stages, Msln, C3, and Efemp1 were expressed only in mature stages. "The findings of our research can enhance the current understanding of epicardial cells, contributing to the development of more effective cardiac regenerative therapy strategies. This, in turn, improves the prognosis of patients with myocardial infarction and propels advancements in the field of cardiac repair," comments author Dr. Ling Zhang. Together, these articles enlighten us with a deeper understanding of cellular mechanisms at the single-cell and spatial levels, offering hope for improved treatment strategies in the future. Reference Title of original paper: Temporal dynamics of microglia-astrocyte interaction in neuroprotective glial scar formation after intracerebral hemorrhage Journal: Journal of Pharmaceutical Analysis DOI: Media contact Mengjie Wang 367011@email4pr.com Xi'an, China +86-(0)29-88960092 View original content to download multimedia: SOURCE Journal of Pharmaceutical Analysis

14 Mar 2023

·www.prnewswire.com

SenesTech Working with TriptoBIO on Biosynthetic Triptolide

PHOENIX, March 14, 2023 /PRNewswire/ -- SenesTech, Inc. (NASDAQ: SNES, "SenesTech" or the "Company"), () the rodent fertility control experts and inventors of the only EPA registered contraceptive for male and female rats, ContraPest®, today confirmed news reports that the Company has been working with the Danish company TriptoBIO on the development of biosynthetic triptolide, one of the active ingredients in ContraPest. "We have been working with TriptoBIO for quite some time on biosynthetic triptolide, and have a letter of intent in place for its development and will be working collaboratively to have it approved by the EPA," said Joel Fruendt, SenesTech's CEO. "The recent press in Europe about their advances has highlighted the efficacy and sustainability of ContraPest, as well as some of the benefits of a biosynthetic source of triptolide." Mr. Fruendt continued, "From our perspective, biosynthetic triptolide brings two very distinct advantages to ContraPest. One, biosynthetic production is typically more consistent in its quality and availability, compared with botanically derived triptolide from China, our current source. Two, biosynthetic production is typically much less expensive than botanical purification, allowing us to lower the price of ContraPest and greatly expand our market domestically and internationally." "Working together, SenesTech and TriptoBIO have the aligned mission to change the world of pest management for the better," Mr. Fruendt concluded. About SenesTech We are the experts in rat fertility control. Our passion is to create a healthy environment by better controlling rat pest populations. We keep an inescapable truth in mind. Two rats and their descendants can be responsible for the birth of up to 15,000 pups after a year. We invented ContraPest, the only U.S. EPA registered contraceptive for male and female rats. ContraPest fits seamlessly into all integrated pest management programs, greatly improving the overall goal of effective rat management. We strive for clean cities, efficient businesses, and happy households – with a product that was designed to be effective and sustainable without killing rats. At SenesTech, we are committed to improving the health of the world by humanely managing animal populations through fertility control. For more information visit and . Safe Harbor Statement This press release contains "forward-looking statements" within the meaning of federal securities laws, and we intend that such forward-looking statements be subject to the safe harbor created thereby. Such forward-looking statements include, among others, our belief that the surge of acceptance of ContraPest will be key to building on our growth trend and even accelerating it in 2023. Forward-looking statements may describe future expectations, plans, results or strategies and are often, but not always, made through the use of words such as "believe," "may," "future," "plan," "will," "should," "expect," "anticipate," "eventually," "project," "estimate," "continuing," "intend" and similar words or phrases. You are cautioned that such statements are subject to risks, uncertainties and other factors that could cause actual results to differ materially from those reflected by such forward-looking statements. Such factors include, among others, the impacts and implications of the COVID-19 pandemic, the successful commercialization of our products, market acceptance of our products, regulatory approval and regulation of our products and other factors and risks identified from time to time in our filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K for the fiscal year ended December 31, 2021, our Registration Statement on Form S-1, filed with the Securities and Exchange Commission on October 24, 2022, as amended on November 15, 2022, and the final prospectus related thereto. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Except as required by law, we do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise. CONTACT: Investors: Robert Blum, Joe Dorame, Joe Diaz, Lytham Partners, LLC, 602-889-9700, [email protected] Press: Nicole Williams, Chief Revenue Officer, SenesTech, Inc., 928-779-4143 Company: Tom Chesterman, Chief Financial Officer, SenesTech, Inc., 928-779-4143 SOURCE SenesTech, Inc.

Drug Approval

100 Deals associated with Triptolide

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12025

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Psoriasis	CN	-	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Preclinical	JP	National Cancer Centre of Singapore Pte Ltd.	-
Inflammation	Preclinical	CN	Fujian Institute of Research on The Structure of Matter	-
Rheumatoid Arthritis	Preclinical	US	-	-
Solid tumor	Preclinical	US	-	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2020	Not Applicable	-	-	MNPs-TP	zexgcakgdb(tyimgylojf) = ilgfldsiyz jlakfqjbgm (wigiopyqsx )	Positive	19 Oct 2020
				Free TP	zexgcakgdb(tyimgylojf) = gbnktdsiew jlakfqjbgm (wigiopyqsx )
2019 ARVO Annual Meeting (ARVO2019)	Not Applicable	Choroidal Neovascularization	-	Triptolide	bjfmplwhoj(ucyqileicn) = kdxipoorag fgpdrizmdg (brnlyopkay )	Positive	01 Jul 2019
				Vehicle	bjfmplwhoj(ucyqileicn) = iobjebjvgj fgpdrizmdg (brnlyopkay )
AACR2017	Not Applicable	Pancreatic Cancer	-	Triptolide	jergmxmxmi(tqjoifufbz) = yisvvzzici ccezakcxik (npmahqecef )	-	01 Jul 2017
				triptolide (Control)	jergmxmxmi(tqjoifufbz) = quahnxscde ccezakcxik (npmahqecef )
ASN2014	Not Applicable	Polycystic Kidney, Autosomal Dominant	-	Tripterygium wilfordii (TW) 1 mg/kg/d	gidbkxjpfc(idaxljnzrx) = fgvuafwmgh scpdydzcot (zbbitidqko ) View more	Positive	11 Nov 2014
				Losartan	lahyqqmubw(gmyewnpzlp) = oewcdphpge fozucgyvqt (dqkvkhfogp ) View more
ARVO2011	Not Applicable	-	-	Triptolide	yskwkhjupj(tneycrcejq) = qzusolndak sohsxdjhgz (asnavzofgi, ± 2)	-	01 Apr 2011
				EGF	yskwkhjupj(tneycrcejq) = zfeirvbhji sohsxdjhgz (asnavzofgi, ± 2)

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