์—ฐ๊ตฌ์šฉ

TH5487 OGG1 inhibitor

์ œํ’ˆ ๋ฒˆํ˜ธS8913

TH5487 is a selective active-site inhibitor of 8-oxoguanine DNA glycosylase 1 (OGG1) with IC50 of 342 nM.
TH5487 OGG1 inhibitor Chemical Structure

ํ™”ํ•™ ๊ตฌ์กฐ

๋ถ„์ž๋Ÿ‰: 541.18

๋ฐ”๋กœ๊ฐ€๊ธฐ

ํ’ˆ์งˆ ๊ด€๋ฆฌ (Quality Control)

๋ฐฐ์น˜: ์ˆœ๋„: 99.99%
99.99

ํ™”ํ•™ ์ •๋ณด, ๋ณด๊ด€ ๋ฐ ์•ˆ์ •์„ฑ (Chemical Information, Storage & Stability)

๋ถ„์ž๋Ÿ‰ 541.18 ํ™”ํ•™์‹

C19H18BrIN4O2

๋ณด๊ด€ (์ˆ˜๋ น์ผ๋กœ๋ถ€ํ„ฐ) 3 years -20ยฐC powder
CAS ๋ฒˆํ˜ธ 2304947-71-3 -- ์›์•ก ๋ณด๊ด€

๋™์˜์–ด N/A Smiles C1CN(CCC1N2C3=C(C(=CC=C3)Br)NC2=O)C(=O)NC4=CC=C(C=C4)I

์šฉํ•ด๋„ (Solubility)

In vitro
๋ฐฐ์น˜:

DMSO : 10 mg/mL (18.47 mM)
(์ˆ˜๋ถ„์œผ๋กœ ์˜ค์—ผ๋œ DMSO๋Š” ์šฉํ•ด๋„๋ฅผ ๊ฐ์†Œ์‹œํ‚ฌ ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ์‹ ์„ ํ•˜๊ณ  ๋ฌด์ˆ˜ DMSO๋ฅผ ์‚ฌ์šฉํ•˜์‹ญ์‹œ์˜ค.)

Water : Insoluble

Ethanol : Insoluble

๋ชฐ๋†๋„ ๊ณ„์‚ฐ๊ธฐ

์งˆ๋Ÿ‰ ๋†๋„ ๋ถ€ํ”ผ ๋ถ„์ž๋Ÿ‰
ํฌ์„ ๊ณ„์‚ฐ๊ธฐ ๋ถ„์ž๋Ÿ‰ ๊ณ„์‚ฐ๊ธฐ

In vivo
๋ฐฐ์น˜:

์ƒ์ฒด ๋‚ด ์ œํ˜• ๊ณ„์‚ฐ๊ธฐ (ํˆฌ๋ช…ํ•œ ์šฉ์•ก)

1๋‹จ๊ณ„: ์•„๋ž˜ ์ •๋ณด ์ž…๋ ฅ (๊ถŒ์žฅ: ์‹คํ—˜ ์ค‘ ์†์‹ค์„ ๊ณ ๋ คํ•˜์—ฌ ์ถ”๊ฐ€ ๋™๋ฌผ ํฌํ•จ)

mg/kg g ฮผL

2๋‹จ๊ณ„: ์ƒ์ฒด ๋‚ด ์ œํ˜• ์ž…๋ ฅ (์ด๊ฒƒ์€ ๊ณ„์‚ฐ๊ธฐ์ผ ๋ฟ ์ œํ˜•์ด ์•„๋‹™๋‹ˆ๋‹ค. ์šฉํ•ด๋„ ์„น์…˜์— ์ƒ์ฒด ๋‚ด ์ œํ˜•์ด ์—†๋Š” ๊ฒฝ์šฐ ๋จผ์ € ๋‹น์‚ฌ์— ๋ฌธ์˜ํ•˜์‹ญ์‹œ์˜ค.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

๊ณ„์‚ฐ ๊ฒฐ๊ณผ:

์ž‘์—… ๋†๋„: mg/ml;

DMSO ์›์•ก ์ค€๋น„ ๋ฐฉ๋ฒ•: mg ์•ฝ๋ฌผ ์‚ฌ์ „ ์šฉํ•ด ฮผL DMSO ( ์›์•ก ๋†๋„ mg/mL, ๋†๋„๊ฐ€ ํ•ด๋‹น ์•ฝ๋ฌผ ๋ฐฐ์น˜์˜ DMSO ์šฉํ•ด๋„๋ฅผ ์ดˆ๊ณผํ•˜๋Š” ๊ฒฝ์šฐ ๋จผ์ € ๋‹น์‚ฌ์— ๋ฌธ์˜ํ•˜์‹ญ์‹œ์˜ค. )

์ƒ์ฒด ๋‚ด ์ œํ˜• ์ค€๋น„ ๋ฐฉ๋ฒ•: ์ทจํ•˜๋‹ค ฮผL DMSO ์›์•ก, ๋‹ค์Œ ์ถ”๊ฐ€ฮผL PEG300, ํ˜ผํ•ฉํ•˜๊ณ  ํˆฌ๋ช…ํ•˜๊ฒŒ ํ•œ ๋‹ค์Œ ์ถ”๊ฐ€ฮผL Tween 80, ํ˜ผํ•ฉํ•˜๊ณ  ํˆฌ๋ช…ํ•˜๊ฒŒ ํ•œ ๋‹ค์Œ ์ถ”๊ฐ€ ฮผL ddH2O, ํ˜ผํ•ฉํ•˜๊ณ  ํˆฌ๋ช…ํ•˜๊ฒŒ ํ•ฉ๋‹ˆ๋‹ค.

์ƒ์ฒด ๋‚ด ์ œํ˜• ์ค€๋น„ ๋ฐฉ๋ฒ•: ์ทจํ•˜๋‹ค ฮผL DMSO ์›์•ก, ๋‹ค์Œ ์ถ”๊ฐ€ ฮผL ์˜ฅ์ˆ˜์ˆ˜ ๊ธฐ๋ฆ„, ํ˜ผํ•ฉํ•˜๊ณ  ํˆฌ๋ช…ํ•˜๊ฒŒ ํ•ฉ๋‹ˆ๋‹ค.

์ฐธ๊ณ : 1. ๋‹ค์Œ ์šฉ๋งค๋ฅผ ์ถ”๊ฐ€ํ•˜๊ธฐ ์ „์— ์•ก์ฒด๊ฐ€ ํˆฌ๋ช…ํ•œ์ง€ ํ™•์ธํ•˜์‹ญ์‹œ์˜ค.
2. ์šฉ๋งค๋ฅผ ์ˆœ์„œ๋Œ€๋กœ ์ถ”๊ฐ€ํ•ด์•ผ ํ•ฉ๋‹ˆ๋‹ค. ๋‹ค์Œ ์šฉ๋งค๋ฅผ ์ถ”๊ฐ€ํ•˜๊ธฐ ์ „์— ์ด์ „ ์ถ”๊ฐ€์—์„œ ์–ป์€ ์šฉ์•ก์ด ํˆฌ๋ช…ํ•œ ์šฉ์•ก์ธ์ง€ ํ™•์ธํ•ด์•ผ ํ•ฉ๋‹ˆ๋‹ค. ์™€๋™, ์ดˆ์ŒํŒŒ ๋˜๋Š” ๋œจ๊ฑฐ์šด ๋ฌผ ์ค‘ํƒ•๊ณผ ๊ฐ™์€ ๋ฌผ๋ฆฌ์  ๋ฐฉ๋ฒ•์„ ์‚ฌ์šฉํ•˜์—ฌ ์šฉํ•ด๋ฅผ ๋„์šธ ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค.

์ž‘์šฉ ๋ฉ”์ปค๋‹ˆ์ฆ˜ (Mechanism of Action)

Targets/IC50/Ki
OGG1
(Cell-free assay)
342 nM
์‹œํ—˜๊ด€ ๋‚ด(In vitro)

TH5487 increases the melting temperature of OGG1 in human cells. This compound impaires repair of genomic 8-oxoG induced by KBrO3. It preventes OGG1 binding to its genomic substrate in living cells.

์ƒ์ฒด ๋‚ด(In vivo)

To assess whether TH5487 could down-regulate chemotactic (C-C and C-X-C) mediators in vivo, we challenge mouse lungs with TNFα and profile the gene expression of proinflammatory mediators. This compound is efficacious in vivo, suggesting that it could be used for the treatment of inflammatory conditions.

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