Delving into the Latest Updates on 5(R)-Hydroxytriptolide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

5(R)-5-hydroxytriptolide, 5-Hydroxytriptolide, Hydroxytriptolide

+ [7]

Target

NOS2

Action

inhibitors, stimulants

Mechanism

NOS2 inhibitors(Nitric oxide synthase, inducible inhibitors), Immunostimulants

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases+ [1]

Active Indication

Acquired Immunodeficiency SyndromeDiabetic Nephropathies

Inactive Indication

Rheumatoid Arthritis

Originator Organization

Shanghai Institute of Materia Medica Chinese Academy of Sci

Active Organization

Shanghai Institute of Materia Medica Chinese Academy of Sci

Shanghai Pudong New District Zhoupu Hospital

Shanghai Pharmaceuticals Holding Co., Ltd.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationSpecial Review Project (China)

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Structure/Sequence

Molecular FormulaC20H24O7

InChIKeyOKRSVUYYCJPECG-LFGMFVMYSA-N

CAS Registry583028-68-6

[Translation] A multicenter, randomized, double-blind, double-dummy, positive drug parallel controlled phase II clinical study on the efficacy and safety of Lei Teng Shu in the treatment of postmenopausal women with inadequate response to methotrexate and moderate to severe active rheumatoid arthritis

主要目的观察雷腾舒治疗甲氨蝶呤反应不足、绝经后、中重度活动性类风湿关节炎患者的疗效次要目的观察雷腾舒在上述受试者中安全性探索性目的探索雷腾舒的群体药代动力学（PopPK）特征、暴露-反应（E-R）关系

[Translation]

Primary objective: To observe the efficacy of Leitengshu in the treatment of postmenopausal patients with moderate to severe active rheumatoid arthritis who have insufficient response to methotrexate Secondary objective: To observe the safety of Leitengshu in the above subjects Exploratory objective: To explore the population pharmacokinetic (PopPK) characteristics and exposure-response (E-R) relationship of Leitengshu

Start Date22 Jun 2020

Sponsor / Collaborator

Shanghai Pharmaceuticals Holding Co., Ltd.

[+1]

NCT04084444

/ CompletedPhase 2

Efficacy and Safety of T8 on Treating Chronic Abnormal Immune Activation in HIV/AIDS Patients: A Multicenter, Randomized, Double-blind, Dose-finding, Placebo-controlled Study

This is a multicenter, randomized, double-blind, dose-finding, placebo-controlled study in patients with chronic HIV infection and inadequate immune restoration treated with long-term highly active antiretroviral therapy (HAART). A total of 150 eligible subjects will be selected and randomized at a ratio of 1:1:1 into T8 0.5 mg QD, 1 mg QD, and placebo group, with background HAART unchanged, for 48 consecutive weeks.

Start Date25 Dec 2019

Sponsor / Collaborator

Shanghai Pharmaceuticals Holding Co., Ltd.

CTR20191397

/ CompletedPhase 2

雷腾舒治疗HIV患者慢性异常免疫激活的有效性和安全性—多中心随机双盲、剂量探索安慰剂平行对照探索性临床试验

[Translation] Efficacy and safety of Leitengshu in the treatment of chronic abnormal immune activation in HIV patients: a multicenter, randomized, double-blind, dose-finding, placebo-controlled, parallel exploratory clinical trial

探索雷腾舒治疗艾滋病患者慢性异常免疫激活的有效性和安全性，为III期临床试验提供剂量选择依据。

[Translation]

Explore the effectiveness and safety of Leitengshu in treating chronic abnormal immune activation in AIDS patients and provide a basis for dose selection for Phase III clinical trials.

Start Date18 Dec 2019

Sponsor / Collaborator

Shanghai Pharmaceuticals Holding Co., Ltd.

[+1]

100 Clinical Results associated with 5(R)-Hydroxytriptolide

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100 Translational Medicine associated with 5(R)-Hydroxytriptolide

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100 Patents (Medical) associated with 5(R)-Hydroxytriptolide

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61

Literatures (Medical) associated with 5(R)-Hydroxytriptolide

01 Feb 2025·Drug Metabolism and Bioanalysis Letters

Precision Formulation of Ocular Films for Eye Infections using Innovative Quality by Design Optimization

Article

Author: Chinthaginjala, Haranath ; Maddileti, Repollu

Aim:The current study focused on formulating ocular films embedded with levofloxacin for the treatment of conjunctivitis by employing the solvent-casting technique.Methods:These films were formulated with gelatin, Aloe barbadensis leaves mucilage (ABLM), and HPMC K4M to enhance the therapeutic effectiveness of levofloxacin. Various evaluations were carried out to confirm the quality and stability of the films, including assessments of thickness, weight uniformity, uniformity in LFX, % loss of moisture, and permeation. In vitro drug release studies were conducted to simulate ocular environments and analyze the precise release of LFX.Results:The films exhibited uniform thickness (0.15–0.19 mm) and weight (61.85–65.54 mg) with a consistent film area (0.502 cm²). LFX content ranged from 85.66% to 97.03%, with T-6 being the most uniform. Moisture loss was found to be 7.98–9.55%, and absorption (highest in T-6, i.e., 18.05%) increased with gelatin. LFX permeation peaked at 97.03% (T-6) in 24-h diffusion studies. T-8 demonstrated exceptional mucoadhesion (>10 h), and ANOVA confirmed the important influence of gelatin, ABLM, and HPMC K4M on LFX content (F-value: 129.91, p=0.0010).Conclusion:The study concluded that combining ABLM with HPMC K4M enabled consistent, diffusion-controlled release of LFX, offering an effective and sustained formulation for treating conjunctivitis.

01 Dec 2024·European Journal of Medicinal Chemistry

Water-soluble and predictable-release triptolide prodrugs block bleomycin-induced pulmonary fibrosis in mice

Article

Author: Xu, Yan ; Song, Wei ; Li, Wen ; Chen, Yubai ; Wu, Liuying ; Chen, Yong ; Chen, Yuhan ; Peng, Zhihong ; Liang, Meiyu ; Yu, Qin ; Yang, Zhiming ; Yan, Xingting

Idiopathic pulmonary fibrosis (IPF) is a progressive respiratory disease with no known cause. It is characterized by widespread inflammation and structural abnormalities in the alveoli of the lungs, ultimately leading to the development of pulmonary fibrosis. Triptolide (TP), an epoxy-diterpene lactone compound known for its potent anti-inflammatory and antifibrotic effects, was limited clinical use due to poor water solubility and side effects. Two soluble TP prodrugs (PG490-88 and Minnelide) have entered clinical research. However, their activities are based on enzyme metabolism, which is influenced by species-specific differences. In this study, we present water-soluble TP derivatives synthesized by introducing ethylenediamine carbamate groups (TP-DEAs) at the 14-hydroxy position. The introduced groups were found to spontaneously convert into the parent drug through enzyme-independent metabolic conversion. The water solubility and stability of the compounds were examined in vitro. Notably, TP-DEA2 exhibited high water solubility (30.8 mg/mL), exceeding TP solubility by more than 1181-fold. In vitro, TP-DEA2 converted to TP autonomously without the involvement of enzymes. In addition, TP-DEA2 can inhibit the expression of a disintegrin and metalloproteinase 10 (ADAM 10) induced by TGF-β1 and reduce the secretion of a-SMA in fibroblasts. 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.

01 Jan 2024·International Immunopharmacology

(5R)-5-hydroxytriptolide ameliorates diabetic kidney damage by inhibiting macrophage infiltration and its cross-talk with renal resident cells

Article

Author: Jing, Zhao ; Yudie, Fang ; Kaida, Mu ; Xiaorong, Yang ; Yanping, Yang ; Jing, Zhang ; Jinan, Zhang ; Peng, Du ; Xiaofei, An ; Jianbin, Xu

OBJECTIVEDiabetic nephropathy (DN) is the main cause of end-stage renal disease, and there are no targeted treatment options at present. The efficacy of the new immunosuppressive drug (5R)-5-hydroxytriptolide (LLDT8) in improving kidney inflammation has been demonstrated in multiple studies. The present study was intended to investigate the preventive and therapeutic effects of LLDT8 on DN and to reveal its potential pharmacological mechanisms.METHODSThe effects of LLDT8 on liver and kidney functions, and urine microprotein of Streptozotocin (STZ) induced DN mice were detected. The protective effect of LLDT8 on the kidney tissue was observed by pathological staining and transmission electron microscopy. Cell culture experiments were performed to detect the effects of LLDT8 on the expression of chemokines and epithelial-mesenchymal transition (EMT) in high glucose-induced TCMK1 cells using real-time polymerase chain reaction (RT-PCR) and western blot (WB) techniques and to detect the influence of LLDT8 on the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells.RESULTSIn animal experiments, treatment with high-dose LLDT8 (0.25 mg/kg/2d) reduced 24 h urinary albumin excretion, improved structural kidney damage, and delayed fibrosis progression in DN mice. Immunofluorescence results showed that LLDT8 intervention reduced macrophage infiltration in kidney tissues of DN mice. PCR and WB results of kidney tissues showed reduced expressions of chemokines CCL2 and M-CSF1 in the LLDT8 intervention group compared to the DN group. In cellular assays, LLDT8 treatment reduced chemokine secretion in high glucose-induced TCMK1 cells, but had no effect on EMT of TCMK1 cells. LLDT8 treatment reduced the secretion of pro-inflammatory and pro-fibrotic factors in high glucose-induced RAW264.7 cells.CONCLUSIONSThe present study suggests that LLDT8 could effectively inhibit the secretion of pro-inflammatory and pro-fibrotic factors by macrophages, which could alleviate high glucose-induced renal tissue injury and slow down the process of tissue fibrosis and DN.

100 Deals associated with 5(R)-Hydroxytriptolide

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External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acquired Immunodeficiency Syndrome	Phase 2	China	Shanghai Pharmaceuticals Holding Co., Ltd.	18 Dec 2019
Acquired Immunodeficiency Syndrome	Phase 2	China	Shanghai Institute of Materia Medica Chinese Academy of Sci	18 Dec 2019
Rheumatoid Arthritis	Phase 1	China	Shanghai Institute of Materia Medica Chinese Academy of Sci	22 Jun 2020
Rheumatoid Arthritis	Phase 1	China	Shanghai Pharmaceuticals Holding Co., Ltd.	22 Jun 2020
Diabetic Nephropathies	Preclinical	China	Shanghai Pudong New District Zhoupu Hospital	01 Jan 2024