Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto

A compound, alkyl technology, applied in the field of inhibiting T lymphocyte activity and related therapy through 3-deoxyflavonoids, can solve the problem of not being a therapeutic candidate

Inactive Publication Date: 2005-09-14
SYNORX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, clotrimazole is also a potent inhibitor of cytochrome P-450-mediated responses in many mammals, so it is not an ideal therapeutic candidate

Method used

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  • Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto
  • Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto
  • Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0098] Kv1.3 channels were inhibited using the patch clamp method described by Fanger (2000) J. Biol Chem. 276:12249. It can be found from Figure 1 below that at a concentration of 20 μM, luteolin blocked about 25% of the Kv1.3 channel current, and at a concentration of 100 μM, luteolin blocked 100% of the Kv1.3 channel current. The curves are also shown in FIG. 1 . The results clearly demonstrate that luteolin and related 3-deoxyflavonoids are effective in blocking Kv1.3 channels and thus in the treatment of autoimmune diseases.

Embodiment 2

[0099] Example 2 The effect of 3-deoxyflavonoids on the cytotoxicity of T lymphocytes

[0100] A cytotoxic T lymphocyte line (CTL-named CTL264) specific for a peptide antigen (aa 264-272, known as peptide 264) derived from the tumor suppressor protein p53 was used as a target to test luteolin whether it has any effect on CTL cytotoxicity of 264 peptide-pulsed T2 target cells. T2 target cells were pulsed with 264 peptide for 2 hours, labeled with Calceln-AM, and washed three times after 30 minutes. The mixture of T2 cells and CTL264 was incubated for 4 hours. 100 [mu]l of the supernatant was transferred to a 96-well flat bottom microtiter plate and the fluorescence (538 nm) was read to measure calcein released due to cell lysis. We unexpectedly found that luteolin significantly inhibited CTL cytotoxicity against 264-pulsed T2 target cells in a concentration-dependent manner (Fig. 2).

Embodiment 3

[0102]In cytotoxic T lymphocytes, spontaneous calcein release was determined by incubation of target cells in RPMI-10. Maximum calcein release was determined by incubation of target cells in Triton X-100. Data are recorded as the average of three determinations. Figure 3 shows inhibition of calcein release by 3-deoxyflavonoids luteolin and 3',4',5',5,7-quercetin.

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Abstract

The present invention discloses 3-deoxyflavonoid compounds and methods for inhibiting T cell activity and treating diseases and disorders (eg, autoimmune diseases, inflammatory diseases, diabetes, ALS, MS, rheumatoid arthritis, etc.). In some cases, the potency and/or duration of action of luteolin and/or other 3-deoxyflavonoid compounds can be increased by administering these compounds together with rutin, rutin analogs, and/or rutin derivatives. Furthermore, in some cases, first-pass metabolism of luteolin or other 3-deoxyflavonoid compounds can be avoided by administering these compounds parenterally (eg, sublingually, bucally, intranasally, injection, etc.).

Description

[0001] related application [0002] This application claims U.S. Provisional Application 60 / 317.666, filed September 6, 2002, and U.S. Provisional Application, filed August 30, 2002, titled "Parental Administration of 3-Deoxyflavonoids to Avoid First Pass Metabolism" (application serial number to be assigned), the entire contents of which are incorporated herein by reference. field of invention [0003] The present invention relates generally to chemical compositions, formulations and methods of medical treatment, and more particularly to the use of certain substituted 3-deoxyflavonoid compounds for the treatment of autoimmune or inflammatory diseases in mammalian patients Immunosuppressive therapy. Background of the invention [0004] Flavonoids are polyphenolic compounds that are commonly found in foods of plant origin. More than 4000 structurally unique flavonoids have been identified in plant sources (Harborne et al., 1975 The Flavonolds, Academic Press, New York; Cody...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61K31/353A61K31/36A61K31/661A61K31/7048A61P3/10A61P21/00A61P37/06C07D311/30C07D311/32C07D311/36C07D407/04C07D493/04C07F9/655
CPCA61K31/353C07D407/04C07D311/36C07D493/04C07D311/30C07D311/32A61K31/352C07F9/65522A61P21/00A61P37/06A61P3/10
Inventor 托马斯·P·莱希V·J·拉贾迪雅克沙
Owner SYNORX
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