TriptoSar (omtriptolide) / Pierre Fabre - LARVOL DELTA

Water-soluble and predictable-release triptolide prodrugs block bleomycin-induced pulmonary fibrosis in mice. (PubMed, Eur J Med Chem) - "Two soluble TP prodrugs (PG490-88 and Minnelide) have entered clinical research. In vivo, TP-DEA2 transformed into TP, effectively inhibiting fibrosis in the bleomycin group without observed toxicity. Importantly, positive outcomes when administering TP-DEA2 at a later stage post-bleomycin exposure suggest its potential role in treating IPF."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • ADAM10 • TGFB1

Research Progress of Triptolide Against Fibrosis. (PubMed, Drug Des Devel Ther) - "Triptolide and its derivatives (Omtriptolide, Minnelide, (5R)-5-hydroxytriptolide) have been proven to have a variety of pharmacological effects. Under pathological conditions, a toxic dose of TPL has a protective effect on organs. The emergence of TPL derivatives (especially Minnelide) and NPs drug delivery systems promotes the anti-fibrosis effect of TPL and reduces its toxicity, which may be the main direction of anti-fibrosis research in the future."

Journal • Review • Fibrosis • Immunology • Inflammation • Ophthalmology

A phase 1b, open-label, safety, pharmacokinetic, and pharmacodynamic study of an anti–super-enhancer triptolide analogue with nab-paclitaxel plus gemcitabine in patients with metastatic adenocarcinoma of the pancreas. (ASCO-GI 2023) - P1b | "Minnelide(ML), water soluble, novel prodrug of TPL, was recently reported to show promising activity in patients with gastrointestinal malignancies in phase I trial... Eligible patients will have histologically confirmed PDAC and have failed first-line FOLFIRINOX with adequate organ function and performance status...This study is prospectively registered on ClinicalTrials.gov, NCT05557851. Clinical trial information: NCT05557851."

Clinical • Metastases • P1 data • PK/PD data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Utilizing mixture design response surface methodology to determine effective combinations of plant derived compounds as prostate cancer treatments. (PubMed, Cancer Rep (Hoboken)) - "Within the PC3 cells, we show that a combination of berberine, wogonin and docetaxel is just as effective as docetaxel alone. Thus, we provide new combination treatments that are highly effective in vitro for treating androgen-dependent and androgen-independent PC."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Transcriptome analysis of newly established carboplatin-resistant ovarian cancer cell model reveals genes shared by drug resistance and drug-induced EMT. (PubMed, Br J Cancer) - "A newly established research model and two distinct transcriptome analysis approaches identified novel candidate genes enrolled in CBP resistance development and/or CBP-induced EMT and implied that one-gene targeting could be a better approach than signalling pathway inhibition for influencing both phenomena."

Journal • Oncology • Ovarian Cancer • Solid Tumor • PRKAR1A

Transcriptome analysis of newly established carboplatin-resistant ovarian cancer cell model reveals genes shared by drug resistance and drug-induced EMT (Br J Cancer, Nature) - "TMEM200A and PRKAR1B were recognised as potentially involved in both phenomena, also having high predictive and prognostic values for OC patients. CBP-resistant MES-OV CBP8 cells were more sensitive to PI3K/Akt/mTOR pathway inhibitors Rapamycin, Wortmannin, SB216763, and transcription inhibitor Triptolide compared with parental MES-OV cells. When combined with CBP, Rapamycin decreased the sensitivity of parental cells while Triptolide sensitised drug-resistant cells to CBP. Four PI3K/Akt/mTOR inhibitors reduced migration in both cell lines."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer

Transcriptome analysis of newly established carboplatin-resistant ovarian cancer cell model reveals genes shared by drug resistance and drug-induced EMT (Br J Cancer, Nature) - "TMEM200A and PRKAR1B were recognised as potentially involved in both phenomena, also having high predictive and prognostic values for OC patients. CBP-resistant MES-OV CBP8 cells were more sensitive to PI3K/Akt/mTOR pathway inhibitors Rapamycin, Wortmannin, SB216763, and transcription inhibitor Triptolide compared with parental MES-OV cells. When combined with CBP, Rapamycin decreased the sensitivity of parental cells while Triptolide sensitised drug-resistant cells to CBP. Four PI3K/Akt/mTOR inhibitors reduced migration in both cell lines."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer

Integrated Bioinformatic Analysis and Experimental Validation to Reveal the Mechanisms of Xinfeng Capsule Against Rheumatoid Arthritis. (PubMed, Comb Chem High Throughput Screen) - "The combination mechanisms of XFC were elucidated in terms of components and targets and signaling pathways, which may be related to inhibiting the proliferation of synovial cells and inflammation."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • TNFA

Natural biomolecules and derivatives as anticancer immunomodulatory agents. (PubMed, Front Immunol) - "This allows for improved recognition and targeting of cancer cells by the immune system and synergy with chemotherapeutics. In this review, we will discuss several well-known plant-derived biomolecules and examine their potential as immunomodulators, and therefore, as novel immunotherapies for cancer treatment."

Immunomodulating • Journal • Review • Immune Modulation • Immunology • Inflammation • Oncology

Methotrexate and Triptolide regulate Notch signaling pathway by targeting the Nedd4-Numb axis. (PubMed, Int Immunopharmacol) - "Interestingly, we found that a monomeric drug, Triptolide, is capable of alleviating the inhibitory effect of MTX on Notch signaling pathway. This study promotes our understanding of MTX-mediated regulation of Notch signaling and could provide ideas to alleviate MTX-induced myelosuppression."

Journal • Dermatology • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Leukemia • Oncology • Psoriasis • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • NOTCH1

Predicting Modifiers of Genotype-Phenotype Correlations in Craniofacial Development. (PubMed, Int J Mol Sci) - "Of these, we found that vinblastine, a microtubule inhibitor, and clofibric acid, a PPAR-alpha agonist, did indeed worsen the gata3 phenotype. The Topoisomerase II and RNA-pol II inhibitors daunorubicin and triptolide, respectively, lessened the phenotype. GO analysis identified Wnt signaling and RNA polymerase function as being enriched in our RNA-seq data, consistent with the mechanism of action of some of the chemicals. Our study illustrates multiple potential pathways for Gata3 function, and demonstrates a systematic, unbiased process to identify modifiers of genotype-phenotype correlations."

Journal • GATA3

Pharmacokinetic Study of Triptolide Nanocarrier in Transdermal Drug Delivery System-Combination of Experiment and Mathematical Modeling. (PubMed, Molecules) - "This research will provide a new technology and method for the study of the pharmacokinetics of traditional Chinese medicine transdermal drug delivery. It has important theoretical and practical significance in clarifying the metabolic transformation of percutaneous drug absorption and screening for appropriate drugs and dosage forms of transdermal drug delivery."

Journal • PK/PD data • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Nephrology • Oncology • Ophthalmology • Pancreatic Cancer • Polycystic Kidney Disease • Renal Disease • Solid Tumor

Phase I study of Minnelide and paclitaxel combination chemotherapy in refractory gastric cancer (GC). (ASCO-GI 2023) - "Background: Minnelide is a prodrug that rapidly releases the active compound triptolide when exposed to phosphatases in the bloodstream. Minnelide in combination with weekly paclitaxel demonstrated promising anti-tumor activity with durable responses in refractory AGC. Clinical trial information: Underreview."

IO biomarker • P1 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PD-L1

Triptolide injection reduces Alzheimer's disease-like pathology in mice. (PubMed, Synapse) - "Additionally, triptolide reduced the expression of inflammatory cytokines and decreased oxidative damage in AD-like mice. Our study suggests that triptolide attenuates AD-like changes in the mouse brain."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Ophthalmology • IL1B • TNFA

Screening of major hepatotoxic components of Tripterygium wilfordii based on hepatotoxic injury patterns. (PubMed, BMC Complement Med Ther) - "Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, triptotriterpenic acid A and triptobenzene H might be the main hepatotoxic components of TwFH. Among them, only triptotriterpenic acid A presents direct hepatotoxicity. Triptobenzene H exerts indirect liver damage by activating macrophages. Parthenolide, triptolide, triptonide, celastrol, and demethylzeylasteral can directly and indirectly cause liver injury."

Journal • Acute Myelogenous Leukemia • Hepatology • Immunology • Inflammation • Inflammatory Arthritis • Liver Failure • Ophthalmology • Rheumatoid Arthritis • Rheumatology • IL1B • TNFA

The Anti-Inflammatory and Immunomodulatory Activities of Natural Products to Control Autoimmune Inflammation. (PubMed, Int J Mol Sci) - "Here, we describe the basic characteristics, mechanisms of action, and preventive/therapeutic applications of 5 well-characterized natural product compounds (Resveratrol, Curcumin, Boswellic acids, Epigallocatechin-3-gallate, and Triptolide). These compounds have been tested extensively in animal models of autoimmunity as well as in limited clinical trials in patients having the corresponding diseases. We have focused our description on predominantly T cell-mediated diseases, such as rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, ulcerative colitis, and psoriasis."

Immunomodulating • Journal • Review • CNS Disorders • Dermatology • Diabetes • Gastroenterology • Gastrointestinal Disorder • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Metabolic Disorders • Multiple Sclerosis • Psoriasis • Rheumatoid Arthritis • Rheumatology • Type 1 Diabetes Mellitus • Ulcerative Colitis

Minnelide combined with Angptl3 knockout completely protects mice with adriamycin nephropathy via suppression of TGF-β1-Smad2 and p53 pathways. (PubMed, Int Immunopharmacol) - "Minimal change disease (MCD) is the common type of nephrotic syndrome in children. In Angptl3 knockout primary podocytes, triptolide alleviates ADR-induced decreases in nephrin, podocin and cd2ap, upregulation of Bax and downregulation of Bcl-2. Overall, our study shows that minnelide combined with Angptl3 knockout completely protects mice with AN by inhibiting the TGF-β1-smad2 and p53 pathways."

Journal • Preclinical • Fibrosis • Glomerulonephritis • Immunology • Nephrology • Oncology • Renal Disease • BAX • BCL2 • IL1B • IL6 • SMAD2 • TGFB1 • TNFA

Triptolide inhibits intrahepatic cholangiocarcinoma growth by suppressing glycolysis via the AKT/mTOR pathway. (PubMed, Phytomedicine) - "Taken together, we revealed that TP suppressed ICC growth by suppressing glycolysis via the AKT/mTOR pathway and may provide a potential therapeutic target for ICC treatment."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Immunology • Oncology • Ophthalmology • Solid Tumor

Triptolide leads to hepatic intolerance to exogenous lipopolysaccharide and natural-killer-cell mediated hepatocellular damage by inhibiting MHC class I molecules. (PubMed, Phytomedicine) - "The TP-induced inhibition of hepatocyte MHC-I molecules expression leads to hepatic intolerance to exogenous LPS and NK-cell mediated cytotoxicity against self-hepatocytes. These findings shed light on the toxicity of traditional Chinese medicines administered for their immunomodulatory effects."

Journal • Hepatology • Immune Modulation • Inflammation • Liver Failure • Ophthalmology • IFNA1 • IFNG

In vitro "benefit-risk" evaluation and network regulation mechanism of Colquhounia Root Tablets and its key material basis (PubMed, Zhongguo Zhong Yao Za Zhi) - "In conclusion, Colquhounia Root Tablets exerts similar effects on rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy to triptolide and celastrol, but the toxicity was lower. PI3 K/HIF1α/NOS signaling pathway may be the common pathway of Colquhounia Root Tablets in the treatment of the three diseases."

Benefit-risk assessment • Journal • Preclinical • Diabetic Nephropathy • Glomerulonephritis • Hepatology • Immunology • Inflammatory Arthritis • Liver Failure • Nephrology • Ophthalmology • Renal Disease • Rheumatoid Arthritis • Rheumatology • HIF1A • NPHS1

Modulating tumour vascular normalisation using triptolide-loaded NGR-functionalized liposomes for enhanced cancer radiotherapy. (PubMed, J Liposome Res) - "The results obtained showed that NGR-PEG-TP-LPs could modulate tumour vascular normalisation to increase the oxygen content of the tumour microenvironment and enhance the efficacy of radiotherapy. Further, liver and kidney toxicity tests indicated that NGR-PEG-TP-LPs are safe for application in cancer treatment."

Journal • Oncology

Network pharmacology, molecular docking and bioinformatics reveal the mechanism of Tripterygii Wilfordii against Osteosarcoma. (PubMed, Medicine (Baltimore)) - "Upregulation of the cellular tumor antigen p53 (TP53) gene and downregulation of peroxisome proliferator-activated receptor gamma (PPARG) and signal transducer and activator of transcription 1-alpha/beta (STAT1) genes can prolong the survival time of patients with OS. Triptolide, kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5 methyl-coumarin-3)-coumarin have a relatively high potential to become a treatment for patients with OS and improve 5-year survival of OS patients."

Journal • Immune Modulation • Inflammation • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • PPARG • STAT1

pH-sensitive nano-polyelectrolyte complexes with arthritic macrophage-targeting delivery of triptolide. (PubMed, Int J Pharm) - "It is noteworthy that after treatment for 14 days with 100 μg/kg of TP, TP/PNPs significantly facilitated arthritic symptom remission, protected cartilage, and mitigated inflammation of antigen-induced arthritis (AIA) rats, whereas the systematic side-effects of TP were reduced. In this study, an effective drug delivery strategy was proposed for the treatment of RA."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway. (PubMed, Chin J Integr Med) - "KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Osteoporosis • Rheumatoid Arthritis • Rheumatology • AKT1 • FGF2

Activation of cDCs and iNKT cells contributes to triptolide-induced hepatotoxicity via STING signaling pathway and endoplasmic reticulum stress. (PubMed, Cell Biol Toxicol) - "ER stress inhibitor, 4-phenylbutyrate (4-PBA), also suppressed iNKT cell activation and liver injury, which might be regulated by the STING signaling pathway. Our results demonstrated the possible mechanisms underlying TP-induced hepatoxicity, where the activation of cDCs and iNKT cells was stimulated by upregulated STING signaling and increased ER stress as a result of TP administration."

Journal • Hepatology • Immune Modulation • Inflammation • Liver Failure • CD1D • IL12A