58053-83-1

Usage

Uses

Used in Pharmaceutical Industry:
17β-hydroxy Wortmannin is used as a research tool for studying the role of PI3K in various cellular processes, including signal transduction, cell growth, and survival. Its ability to inhibit PI3K and mTOR makes it a valuable compound for investigating the underlying mechanisms of these pathways and their potential as therapeutic targets.
Used in Cancer Research and Treatment:
17β-hydroxy Wortmannin is used as an inhibitor of PI3K and mTOR for the study of their roles in cancer cell growth and proliferation. Its potent inhibition of these enzymes has made it a promising candidate for the development of targeted cancer therapies, particularly for prostate cancer. 17β-hydroxy Wortmannin has demonstrated the ability to prevent the growth of LNCap prostate cancer cells, with an IC50 value of 1.46 μM.
Used in Drug Design and Modification:
The 17-hydroxyl group present in 17β-hydroxy Wortmannin has been utilized for further chemical modifications, such as pegylation and conjugation with rapamycin. These modifications aim to improve the compound's pharmacokinetic properties, solubility, and overall efficacy as a therapeutic agent. By enhancing the properties of 17β-hydroxy Wortmannin, researchers can develop more effective drugs for the treatment of various diseases, including cancer.

Upstream product

• 108-24-7 acetic anhydride 
• 182203-32-3 (3S,3aS,5R,5bR,6S,11bR)-3,5-Dihydroxy-6-methoxymethyl-3a,5b-dimethyl-2,3,3a,4,5,5b,6,11b-octahydro-1H-7,10-dioxa-cyclopenta[j]acephenanthrylene-8,11-dione 
• 2899-95-8 (8S,9S,10R,11S,13S,14S,17R)-17-((R)-1,2-dihydroxyethyl)-11,17-dihydroxy-10,13-dimethyl-6,7,8, 9,10,11,12,13,14,15,16, 17-dodecahydro-1H-cyclopenta[a] phenanthrene-3 (2H)-one 
• 182203-12-9 Benzoic acid (3aS,6aS,7S,9aS,9bS,11bS)-6a,11b-dimethyl-2-oxo-1,3a,4,6,6a,7,8,9,9a,9b,10,11b-dodecahydro-2H-3,5-dioxa-cyclopenta[a]pyren-7-yl ester 
• 182203-16-3 Benzoic acid (1S,8S,9R,10R,11S,13S,14S,17S)-9,11-dihydroxy-1-hydroxymethyl-10,13-dimethyl-3-oxo-1,3,8,9,10,11,12,13,14,15,16,17-dodecahydro-2-oxa-cyclopenta[a]phenanthren-17-yl ester 
• 182203-20-9 C₂₇H₃₀O₆ 
• 182203-18-5 Benzoic acid (1S,8S,9R,10R,11S,13S,14S,17S)-9,11-dihydroxy-1-methoxymethyl-10,13-dimethyl-3-oxo-1,3,8,9,10,11,12,13,14,15,16,17-dodecahydro-2-oxa-cyclopenta[a]phenanthren-17-yl ester 
• 182203-03-8 C₂₆H₃₁NO₆Se 
• 182203-30-1 Benzoic acid (3S,3aS,5R,5bR,6S,11bR)-5-hydroxy-6-methoxymethyl-3a,5b-dimethyl-8,11-dioxo-2,3,3a,4,5,5b,11,11b-octahydro-1H,6H,8H-7,10-dioxa-cyclopenta[j]acephenanthrylen-3-yl ester 
• 182203-26-5 C₃₀H₃₆O₈ 
• 182203-28-7 C₂₈H₂₈O₈ 
• 182203-22-1 C₂₇H₃₂O₈ 

Downstream Products

• 19545-26-7 wortmannin 

Relevant academic research and scientific papers

Enantioselective Total Synthesis of (+)-Wortmannin

A concise and enantioselective total synthesis of the potent PI3K inhibitor (+)-wortmannin is described. A Pd-catalyzed cascade reaction was first developed to connect a synthon derived from Hajos-Parrish ketone to a furan moiety. The subsequent Friedel-Crafts alkylation of the β-position of a furan ring to an epoxide was optimized to establish the C10 quaternary center. (+)-Wortmannin was eventually accomplished by transformations following a late-stage oxidation of the furan allylic position. Kinome profiling and in vitro enzymatic assays were performed on 17-β-hydroxy-wortmannin and an epoxide analogue.

ANALOGS OF 17-HYDROXYWORTMANNIN AS PI3K INHIBITORS

The present invention relates to compounds of Formula (I): wherein R1, R2, R3, and R8 are defined herein, useful as P13K inhibitors.

Pegylated wortmannin and 17-hydroxywortmannin conjugates as phosphoinositide 3-kinase inhibitors active in human tumor xenograft models

Phosphoinositide 3-kinase (PI3K) is an important target for cancer chemotherapy due to the deregulation of its signaling pathway in a wide spectrum of human tumors. Wortmannin and its analogues are potent PI3K inhibitors whose therapeutic use has been impeded by inherent defects such as instability and toxicity. Pegylation of wortmannin and 17-hydroxywortmannin gives rise to conjugates with improved properties, including a higher therapeutic index. Pegylated 17-hydroxywortmannin (8, PWT-458) has been selected for further development.

Water soluble wortmannin derivatives

This invention relates to soluble derivatives of wortmannin that utilizes water-soluble polymers as carriers for a drug and includes compounds having the structures as described within the specification.

The first chemical synthesis of wortmannin by starting from hydrocortisone

The first chemical synthesis of wortmannin, a potent and specific inhibitor of PI 3-kinases, was achieved by starting from commercially available and optically pure hydrocortisone.

Studies on the mechanism of phosphatidylinositol 3-kinase inhibition by wortmannin and related analogs

Wortmannin, a fungal metabolite, was identified as a potent inhibitor (IC50 = 4.2 nM) of phosphatidylinositol 3-kinase (PI 3-kinase). Due to the importance of PI 3-kinase in several intracellular signaling pathways, structure-activity studies on wortmannin analogs were performed in an effort to understand the structural requirements necessary for PI 3-kinase inhibition. Since wortmannin is an irreversible inhibitor of PI 3-kinase, it was postulated that covalent attachment at the electrophilic C-21 site was a possible mode of action for PI 3-kinase inhibition. We have prepared various wortmannin analogs which address the possibility of this mechanism. Of particular interest are compounds which affect the C-21 position of wortmannin either sterically or electronically. Our results support the conclusion that nucleophilic addition by the kinase onto the C-21 position of wortmannin is required for inhibition of PI 3-kinase by wortmannin analogs. Additionally, we have prepared several D-ring analogs of wortmannin, and their activities are reported herein. We conclude that the wortmannin D ring is an important recognition site since modifications have such a dramatic effect on inhibitor potency. Finally, the identification of 17β- hydroxywortmannin represents the first reported subnanomolar inhibitor of PI 3-kinase. These studies, along with in vivo antitumor experiments, suggest that the mechanism of PI 3-kinase inhibition correlates to the associated toxicity observed with wortmannin-based inhibitors of PI 3-kinase.