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Aryl hydrocarbon receptor antagonists and methods of use

A technology of aromatic hydrocarbon receptors and modulators, applied in biochemical equipment and methods, pharmaceutical formulations, anti-tumor drugs, etc., can solve problems such as detection and treatment difficulties

Pending Publication Date: 2021-08-13
美真达治疗公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cancer or malignancy rapidly metastasizes and grows in an uncontrolled manner, making timely detection and treatment extremely difficult

Method used

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  • Aryl hydrocarbon receptor antagonists and methods of use
  • Aryl hydrocarbon receptor antagonists and methods of use
  • Aryl hydrocarbon receptor antagonists and methods of use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1373] Example 1: High-throughput screening to identify novel aryl hydrocarbon receptor (the AHR) antagonist

[1374] Screening principle

[1375] With dioxin responsive element (DRE) firefly luciferase reporter constructs were transfected HepG2 hepatocellular carcinoma cells. Luciferase Transcriptional activation aryl hydrocarbon receptor (the AHR) agonists VAF347. Add AHR antagonist inhibition and result in loss of signal analysis of luciferase transcription. The aim of this study was to discover new AHR antagonist.

[1376] HepG2 cells transfected

[1377] Firefly luciferase reporter element hepatocellular carcinoma cell line HepG2 reaction dioxin constructs were transfected using TransIT transfection system. Prior to transfection, HepG2 cells (Sigma) in Eagle's Modified Essential Medium (Sigma) + 2mM glutamine (Sigma) + 1% non-essential amino acids (Sigma) + 10% fetal bovine serum (Hyclone) to 90% the culture confluency and harvested and counted (BioradTC20 cell counter). The ...

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PUM

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Abstract

The disclosure relates to aryl hydrocarbon receptor antagonists as well as methods of modulating aryl hydrocarbon receptor activity and expanding hematopoietic stem cells by culturing hematopoietic stem or progenitor cells in the presence of these agents. Additionally, the disclosure provides methods of treating various pathologies, such as cancer, by administration of these aryl hydrocarbon receptor antagonists. Additionally, the disclosure provides methods of treating various pathologies in a patient by administration of expanded hematopoietic stem cells. The disclosure further provides kits containing aryl hydrocarbon receptor antagonists that can be used for the expansion of hematopoietic stem cells. The disclosure further relates to pharmaceutical compositions comprising the compounds and methods of treating or preventing a disease in which aryl hydrocarbon receptor plays a role.

Description

<000369>The present application claims priority to US Application for US Application No. 62 / 882, 838, filed on August 5, 2019, filed on September 4, 2018, which is incorporated herein by reference. Technical field [0002] The present invention relates to a method for treating or preventing a disease-proof disease, for example, an aromatic hydrocarbon receptor antagonist, treatment or prevention of aromatic hydrocarbon receptor, and treats various hematopoietic changes and by administration of amplified hematopoietic stem cells. Aromatic hydrocarbon receptor antagonists treat various diseases such as cancer. Background technique <00072>Although hematopoietic stem cells have significant treatment potential, it is difficult to obtain a sufficient number of these cells. In particular, hematopoietic stem cells rapidly differentiate during the ex vivo culture process, limiting hematopoietic stem cells (HSCs) as a treatment mode, because of the loss of multi-potential. [0...

Claims

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Application Information

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IPC IPC(8): C07D213/74C07D413/14A61P35/00A61K31/519A61P7/00C07D237/20C07D239/24C07D239/42C07D239/48C07D239/84C07D251/46C07D251/48C07D253/065C07D277/42C07D277/82C07D295/205C07D307/52C07D307/68C07D401/04C07D417/12C07D475/08C07D487/04C07D487/12C07D495/04C07D513/04C07D249/06C07D257/04C07D401/12C07D403/10C07D405/04C07D413/04
CPCC07D495/04C07D277/82C07D295/205C07D239/48C07D213/74C07D277/42C07D251/46C07D475/08C07D417/12C07D239/42C07D239/84C07D487/04C07D253/065C07D239/24C07D401/04C07D307/68C07D307/52C07D487/12C07D237/20C07D251/48C07D513/04C07D249/06C07D257/04C07D403/10C07D405/04C07D401/12C07D413/04C07D413/14A61P35/00A61P7/00A61K45/06G01N2500/10A61K31/5375A61P37/00A61P25/00C07D261/08C07D498/04C07D277/22C07D213/75C12N5/0647C12N2501/999C12N2501/2301C12N2501/2303C12N2501/2306C12N2501/2311C12N2501/22C12N2501/125C12N2501/145C12N2501/14C12N2501/26A61K31/167A61K31/277A61K31/343A61K31/366A61K31/381A61K31/4035A61K31/415A61K31/4155A61K31/416A61K31/4162A61K31/4184A61K31/4192A61K31/4196A61K31/42A61K31/421A61K31/422A61K31/423A61K31/425A61K31/426A61K31/427A61K31/428A61K31/429A61K31/4365A61K31/437A61K31/44A61K31/4412A61K31/443A61K31/4436A61K31/4439A61K31/444A61K31/454A61K31/4545A61K31/47A61K31/4704A61K31/4709A61K31/50A61K31/501A61K31/505A61K31/519A61K31/5377A61K31/55A61K35/28C07C233/81C07C255/60C07D207/34C07D209/44C07D213/82C07D215/38C07D231/56C07D235/18C07D237/24C07D249/04C07D249/12C07D275/04C07D277/28C07D295/135C07D307/91C07D401/14C07D405/12C07D409/12C07D413/12C07D417/04C07D471/04C07D471/14C07D495/14G01N33/5073
Inventor A.博伊塔诺M.库克K.A.冈卡尔维斯M.霍班
Owner 美真达治疗公司
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