195883-06-8

Basic information

• Product Name: Omtriptolide
• Synonyms: OMTRIPTOLIDE;Unii-D36elm729p
• CAS NO: 195883-06-8
• Molecular Formula: C₂₄H₂₈O₉
• Molecular Weight: 460.476
• Mol File: 195883-06-8.mol

Chemical Properties

• Melting Point: 109-111 ºC
• Boiling Point: 691.4±55.0 °C(Predicted)
• Appearance: /
• Density: 1.49
• PKA: 4.36±0.17(Predicted)
• CAS DataBase Reference: Omtriptolide(CAS DataBase Reference)
• NIST Chemistry Reference: Omtriptolide(195883-06-8)
• EPA Substance Registry System: Omtriptolide(195883-06-8)

Safety Data

• Hazardous Substances Data: 195883-06-8(Hazardous Substances Data)

Usage

Uses

Antineoplastic.

Upstream product

• 108-30-5 succinic acid anhydride 
• 38748-32-2 triptolide 

Downstream Products

• 195883-07-9 triptolide succinate tris salt 

Relevant articles and documents

Albumin-conjugated drug is irresistible by single gene mutation of endocytic system: Verification by genome-wide CRISPR-Cas9 loss-of-function screens

Albumin-conjugated drugs attain KRAS mutant cancer targeting through KRAS-enhanced macropinocytosis and intensified lysosomal degradation due to reduced neonatal Fc receptor (FcRn) expression. The cytosolic delivery of active payloads relies on endocytosis and subsequent intracellular processing of albumin delivery vehicles, wherein complex regulatory mechanisms and molecular machineries are closely involved. Despite the obvious merit of KRAS targeting, could such an endocytic process involving extra molecular regulators also bring about extra vulnerabilities to albumin-conjugated drugs, particularly, unexpected drug resistance? To assess such risks, here we performed an unbiased drug resistance mechanism comparison in pancreatic cancer, between free triptolide (TP, a potent cytotoxin) and albumin-conjugated TP, using genome-wide CRISPR-Cas9 loss-of-function screens. GTF2H5, a subunit of GTF2H transcription factor complex, was the only hit identified regardless of forms of TP treatment. With drug efficacy tests on GTF2H5 knockout clones, we further concluded that GTF2H5 deficiency conferred drug resistance primarily due to the pharmacological mechanism of action (MoA) of TP. In addition, molecules previously considered to be able to affect endocytosis and intracellular processing were not enriched during the screening with albumin-conjugated TP. With the aid of genome-wide CRISPR-Cas9 loss-of-function screens, we conclude that the pharmacological resistance of the active payload, rather than any potential loss-of-function mutations in endocytic molecular machineries, is the solely crucial drug resistance mechanism of albumin-conjugated drugs.

Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation

Triptolide, a key ingredient from the traditional Chinese medicinal plant thunder god vine, which has been used to treat inflammation and autoimmune diseases for centuries, has been shown to be an irreversible inhibitor of the XPB subunit of the transcription factor TFIIH and initiation of RNA polymerase II mediated transcription. The clinical development of triptolide over the past two decades has been limited by its toxicity and low water solubility. Herein, we report the development of a glucose conjugate of triptolide, named glutriptolide, which was intended to target tumor cells overexpressing glucose transporters selectively. Glutriptolide did not inhibit XPB activity in vitro but demonstrated significantly higher cytotoxicity against tumor cells over normal cells with greater water solubility than triptolide. Furthermore, it exhibited remarkable tumor control in vivo, which is likely due to sustained stepwise release of active triptolide within cancer cells. These findings indicate that glutriptolide may serve as a promising lead for developing a new mechanistic class of anticancer drugs.

COMPOUND AND USE THEREOF

A compound represented by formula (I), or an isomer, a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate, a solvate, a metabolite, pharmaceutically acceptable salts or a prodrug thereof.

TRIPTOLIDE ANTIBODY CONJUGATES

The antibody-drug conjugates provided herein including embodiments thereof, include the compound triptolide attached to a cancer-specific antibody (e.g., cetuximab) and are, inter alia, useful as highly effective anti-cancer therapeutics. The conjugates provided herein are capable of targeting cancer cells and thereby specifically deliver triptolide to the cancer cell.

Preparation method and application of triptolide-carboxylation chitosan coupling drug

The invention discloses a preparation method and application of a triptolide-carboxylation chitosan coupling drug. The preparation method comprises the following steps: (1) synthesis of intermediate carboxylation triptolide (TP-L); and (2) synthesis of the triptolide-carboxylation chitosan coupling drug (TP-L-CChit). The triptolide-carboxylation chitosan coupling drug (TP-L-CChit) prepared by themethod, as a pro-drug, has application for preparing drugs for treating rheumatoid arthritis, tumors and Alzheimer's disease; the drug is simple in method, easy for production preparation, high in yield and rich and easily obtained in raw materials, the product is high in water solubility, long in biological half life period, high in availability, free of toxic or side effect and good in curativeeffect and is innovation for preparing drugs for treating rheumatoid arthritis, tumors and Alzheimer's disease, and the economic and social benefits are obvious.

GLUCOSE CONJUGATES OF TRIPTOLIDE, ANALOGS AND USES THEREOF

Provided are compounds generated by conjugation of triptolide with glucose to form glucose-triptolide conjugates, provides compounds with effective anti -proliferative activity and improved tolerability as compared to naturally occurring triptolide compounds.

Treatment of acute myeloid leukemia

The invention is directed to the use of an ester derivatives of triptolide, tripdiolide, 16-hydroxytriptolide, a pharmaceutically acceptable salt thereof, or a combination thereof, for the manufacture of a medicament comprising the triptolide prodrug for the treatment of acute myeloid leukemia.

METHOD FOR TREATMENT OF INFLAMMATORY DISORDERS USING TRIPTOLIDE COMPOUNDS

Inflammatory disorders, including obliterative airway disease, renal fibrosis, diabetic nephropathy, and liver fibrosis are treated with immunosuppressive triptolide compounds, in particular triptolide compounds effective to inhibit TGF-β production in a patient afflicted with such a disorder.