Use of T0901317 as a PARP1 inhibitor

A use, technology of trifluoroethyl, applied in the field of application of PARP1 inhibitors

Active Publication Date: 2018-06-26
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Existing studies believe that elevated cholesterol is clearly related to the incidence of tumors, but there is no evidence for cholesterol-related drugs in this regard

Method used

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  • Use of T0901317 as a PARP1 inhibitor
  • Use of T0901317 as a PARP1 inhibitor
  • Use of T0901317 as a PARP1 inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 Detection by Cell-Free PARP1 Enzymatic Reaction System

[0027] The PARP1 activity detection kit was used to construct a cell-free PARP1 enzymatic reaction system, which can activate the activity of PARP1 enzyme in vitro.

[0028] The PARP1 activity detection kit used in the examples was purchased from Trevigen Company, produced in the United States, and the model number is 4676-096-K.

[0029] PARP1 activity detection kit includes buffer, PARP1 recombinant protein, NAD + , single-strand break DNA, recombinant histone 1 (Histone H1).

[0030] Configure the cell-free PARP1 enzymatic reaction system according to the PARP1 activity detection kit. The specific operation steps are as follows: add 50ng PARP1 recombinant protein (PARP1protein) to the buffer solution with a final concentration of 10mmol / L NAD + , The final concentration is 20mg / mL after single-strand break DNA. The final concentration of each component of the buffer solution in the reaction system ...

Embodiment 2

[0037] Embodiment 2 utilizes in vitro cell experiment to detect

[0038] In the in vitro cell experiment, HepG2 (derived from American Type Culture Collection) cells were selected as experimental cells. The inventors treated HepG2 cells with different concentrations of T09013171. For treatment methods, see Huang D, Yang C, WangY, Liao Y, & Huang K. PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPAR gamma in cardiac fibroblasts. Cardiovascular research, 2009, 81(1): 98-107 .

[0039] HepG2 cells were stimulated with T0901317 (iii, 1 μmol / L, 3 μmol / L, 5 μmol / L) or nicotinic acid (iv, 1 μmol / L, 5 μmol / L, 10 μmol / L) for 24 hours, and the concentrations in the above brackets were final concentration.

[0040] PARP1 activity was detected using a PARP1 activity detection kit (purchased from Trevigen, produced in the United States, model number 4676-096-K). For specific methods, refer to the instructions of the kit. Among them, 3AB (10 mmol / L) was used...

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Abstract

The invention relates to N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1- hydroxyl-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide (T0901317 for short) serving as a PARP-1 (poly(ADP-ribose)polymerase-1) inhibitor. The T0901317 belongs to a cholesterol analogue and does not have a cytotoxic effect like that of a usual tumor drug or other PARP-1 inhibitors, and the safety of the T0901317 can be expected. The T0901317 can be widely applied by serving as the medicine for curing cholesterol related diseases such as cardiovascular diseases and tumors.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxyl-1-(trifluoromethyl ) Ethyl]phenyl]-benzenesulfonamide, a hydroxylated cholesterol analogue, as a PARP1 inhibitor. Background technique [0002] N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxyl-1-(trifluoromethyl)ethyl]phenyl]-benzene Sulfonamide, CAS number is 293754-55-9, abbreviated as T0901317, chemical formula is C 17 h 12 f 9 NO 3 S, the molecular weight is 481.33. T0901317 is a potent and selective LXR and FXR agonist. [0003] The above-mentioned compounds all belong to hydroxylated cholesterol analogs and have the effect of lowering cholesterol. In the current research, it is mainly used as an agonist of the liver X receptor (LXR), that is, to activate LXR, such as activating the gene LXRα (liver X receptor α subtype), so the above drugs are widely used in LXR-related research middle. [0004] Poly ADP-rib...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/18A61P9/00A61P35/00A61P3/06
Inventor 黄恺张冯筱黄丹
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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