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-

NCT02115659 / Unknown statusPhase 3IIT

Randomized Controlled Trial of Triptolide-Containing Formulation for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Triptolide was shown in experimental studies to inhibit the cyst formation and growth in ADPKD models, while triptolide-containing formulation was revealed to potentially slow the disease progression in several proteinuric ADPKD patients in our clinical practice. It remains to be shown the effect of triptolide-containing formulation on total kidney volume (TKV) enlargement and renal function protection in ADPKD patients.

Start Date01 Apr 2014

Sponsor / Collaborator

Shanghai Changzheng Hospital

100 Clinical Results associated with Triptolide

100 Translational Medicine associated with Triptolide

100 Patents (Medical) associated with Triptolide

1,703

Literatures (Medical) associated with Triptolide

01 Jan 2025·JOURNAL OF ETHNOPHARMACOLOGY

Exploring the liver toxicity mechanism of Tripterygium wilfordii extract based on metabolomics, network pharmacological analysis and experimental validation

Review

Author: Hua, Yong-Qing ; Duan, Jin-ao ; Duan, Jin-Ao ; Zhou, Guo-Liang ; Su, Shu-Lan ; Shang, Er-Xin ; Yu, Li ; Yu, Hao

ETHNOPHARMACOLOGICAL RELEVANCE:

Tripterygii wilfordii Radix, (TW) as a toxic herbal medicine, is the root of Tripterygium wilfordii Hook. F. , which commonly used in China for the treatment of rheumatoid arthritis and autoimmune diseases, but its severe toxicity, particularly hepatotoxicity, significantly impacts its clinical application.

AIM OF THE STUDY:

The hepatotoxicity and its molecular mechanism of 70% TW ethanol extract (TWE) on male mice were demonstrated based on metabolomics, network pharmacological analysis and experimental validation.

MATERIALS AND METHODS:

The toxic and bioactive ingredients in TWE were quantitative analyzed by Triple quadrupole (TQ) mass spectrometry method. The liver organ index, as well as the liver function indexes AST and ALT were evaluated after administering different doses of TWE for 24 hours, and a pathological change was analyzed in liver tissue. Non-targeted metabolomics using UPLC-QTOF/MS was performed on both the plasma and liver tissue samples in combination with network toxicology to screen for key targets related to TWE toxicity in the liver. These key targets including caspase 3, NF-κB, TLR4, TNF-α, NQO1, and Bcl2 were subsequently verified through Western blotting experiments.

RESULTS:

The six toxic and active ingredients of raphenolactone, ranolactone, triptolide tripterine, wilforlide A, demethylzeylasterain in TWE for the contents of 0.709, 1.408, 0.353, 0.354, 0.882, 0.227 mg.g^-1, respectively. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased and liver index decreased after administration of TWE for 24hr. Pathological analysis showed that TWE could produce toxicity to mouse liver, and its toxicity was dose-dependent. In the high-dose group, TW-D (11.23g/kg) and TW-E (22.46g/kg) caused a large amount of rupture in mouse liver nucleus and a large amount of inflammatory infiltration at the same time. Furthermore, 63 metabolites in plasma and 89 metabolites in the liver tissue were identified. The main metabolic pathways involved glycerol phospholipid metabolism, glycosylphosphatidylinositol-ether lipid metabolism, fatty acid metabolism, sphingomyelin metabolism, and ether lipid metabolism in plasma and liver tissue. Through analysis of the top 10 correlated targets, 6 out of the top 10 selected target proteins exhibited consistent expression patterns with liver injury. The levels of Bcl2 and NQ-O1 decreased with increasing exposure dose. The expression of Caspase 3, NF-κB, TLR4, and TNF-α increased with increasing dose. These findings suggest that protein expression has a regulatory effect at different doses groups compared to the control group.These findings suggest a regulatory effect of protein expression in different dose groups compared to the control group.

CONCLUSION:

The hepatotoxic effects of TWE can increase ALT and AST levels in plasma, leading to hepatic oxidative damage and inflammatory response. The toxic mechanisms that produce are closely related to the regulating of the abnormal metabolites in plasma and liver tissue. Furthermore, the regulating the expression levels of targeted proteins of TNF-α, NF-κB, Caspase 3, NQ-O1, and Bcl2 were confirmed by examining the liver tissue. These data clearly elucidate the toxicity mechanism of TW, laying the foundation for ensuring the quality and safety of drugs.

01 Jan 2025·MICRON

Plant-derived compounds that target histone acetyltransferases inhibit Trypanosoma cruzi proliferation and viability and affect parasite ultrastructure

Article

Author: de Souza, Wanderley ; Zuma, Aline Araujo ; Bortolami, Fernanda Pereira ; Motta, Maria Cristina Machado

Trypanosoma cruzi, the causative agent of Chagas disease, exhibits a chromatin structure and organization similar to that of other eukaryotes, undergoing certain epigenetic modifications, such as histone acetylation and deacetylation. Histone acetyltransferase inhibitors have been frequently applied as therapy agents against tumor cells, but their effects on protozoa have not yet been adequately explored. In this study, the effects of three acetyltransferase inhibitors, curcumin, triptolide and anacardic acid, were investigated on T. cruzi. Curcumin was able to inhibit epimastigote and amastigote proliferation and was the most effective compound. Triptolide also impaired T. cruzi proliferation and, along with curcumin, promoted the unpacking of nuclear heterochromatin and nucleolus disorganization. Anacardic acid did not alter parasite growth or viability, but caused ultrastructural changes, such as mitochondrial swelling and cristae enlargement. None of these compounds affected the microtubule cytoskeleton. These findings indicate that histone acetyltransferase inhibitors, especially curcumin, display the potential to be applied in chemotherapeutic studies against T. cruzi. Our results reinforce the necessity of developing new compounds that can be used successfully in therapy against neglected diseases.

31 Dec 2024·DRUG DELIVERY

Homotypic cell membrane-camouflaged biomimetic PLGA nanoparticle loading triptolide for the treatment of hepatocellular carcinoma

Article

Author: Li, Zhe ; Lan, Jinshuai ; Zhang, Tong ; Ding, Yue ; Wu, Ya

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at -21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.

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	Ischemia	-	MNPs-TP	oraakwdefp(fssfbaqoze) = cdgiprdway crljlvqaye (jhgudivxrh )	Positive	19 Oct 2020
				Free TP	oraakwdefp(fssfbaqoze) = pmujmjucay crljlvqaye (jhgudivxrh )
AACR2017	Not Applicable	Pancreatic Cancer	-	Triptolide	onxjiqxrmx(vkkpjduymk) = ykrdpsnczr qikedlxxhv (ihjhaeqyil )	-	01 Jul 2017
				triptolide (Control)	onxjiqxrmx(vkkpjduymk) = hdhwpqmldj qikedlxxhv (ihjhaeqyil )
ASN2014	Not Applicable	Polycystic Kidney, Autosomal Dominant	-	Tripterygium wilfordii (TW) 1 mg/kg/d	zjurhoshlz(paatgbuvhu) = axfmwjqfug bkgerrclot (gkgvdfdkrk ) View more	Positive	11 Nov 2014
				Losartan	rzofyigihf(heeifvhudk) = enjgafcdeg ijcvydflnp (asqtcitjlg ) View more
ARVO2011	Not Applicable	-	-	Triptolide	pdkojvhlst(bgwgwyzyme) = eqehcfudrj sqlgbfkjmj (fqphwvjkyc, ± 2)	-	01 Apr 2011
				EGF	pdkojvhlst(bgwgwyzyme) = oxfgoiagdu sqlgbfkjmj (fqphwvjkyc, ± 2)

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