TK-129|西域试剂

TK-129,98.0%

产品编号：Bellancom-151483| 分子式：C₁₅H₂₃N₅O₂| 分子量：305.38

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-151483	￥1500.00	杭州北京（现货）
Bellancom-151483	￥2500.00	杭州北京（现货）
Bellancom-151483	￥5500.00	杭州北京（现货）
Bellancom-151483	￥9500.00	杭州北京（现货）

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TK-129

产品介绍

TK-129 是一种口服有效的、低毒的强效 KDM5B 抑制剂 (具有高亲和力; IC₅₀=44 nM)。TK-129 通过抑制 KDM5B 和阻断 KDM5B 相关的 Wnt 通路，来发挥心脏保护作用。TK-129 能在体外减少 Ang II 诱导的心脏成纤维细胞的活化，并在体内减少异丙肾上腺素诱导的心肌重塑和纤维化。TK-129 可用于心血管疾病的研究。

生物活性

TK-129 is an orally active, low-toxicity, potent KDM5B inhibitor (with high affinity; IC₅₀=44 nM). TK-129 exerts cardioprotective effects by inhibiting KDM5B and blocking the KDM5B-associated Wnt pathway. TK-129 reduces ang II-induced activation of cardiac fibroblasts in vitro and reduces isoprenaline-induced myocardial remodelling and fibrosis in vivo. TK-129 can be used in studies of cardiovascular disease.

体外研究

TK-129 mediates inhibition of KDM5B activity significantly reduces the activation, migration, and proliferation of myofibroblasts induced by Ang II in vitro.
TK-129 (10 μM; 48 h) shows low cytotoxicity in NRCFs and NRCMs.
TK-129 (0.1, 0.2, 0.3, 0.4, 0.5 μM; 48 h) can engage toand inhibit KDM5B activity in NRCFs.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay

Cell Line:	NRCFs and NRCMs
Concentration:	10 μM
Incubation Time:	48 h
Result:	Exhibited the cell survival rates were almost more than 90%.

Western Blot Analysis

Cell Line:	NRCFs
Concentration:	0.1, 0.2, 0.3, 0.4, 0.5 μM
Incubation Time:	48 h
Result:	Increased the expression level of KDM5B substrate H3K4me3 protein in a concentration-dependent manner.

体内研究
(In Vivo)

TK-129 (2 g/kg; p.o.; single) shows good bio-safety in mice.
TK-129 (50 mg/kg; p.o.; twice daily for 24 days) effectively reduces isoproterenol-induced pathological myocardial remodeling in vivo.
TK-129 (2 or 10 mg/kg; i.v. or p.o.; single) demonstrates favorable PK properties in vivo.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Wild C57BL/6 mice (8 to 10-week-old; half male and half female).
Dosage:	2 g/kg
Administration:	Oral gavage, single.
Result:	Exhibited all mice in the acute toxicity group survived and gained weight normally, after 2 weeks.

Animal Model:	C57BL/6 mice (isoproterenol (ISO)-induced).
Dosage:	50 mg/kg
Administration:	Oral gavage, twice daily for 24 days.
Result:	Alleviated myocardial remodeling induced by ISO in vivo.

Animal Model:

Male SD Rats (223.5-265.1 g).

Dosage:

2 mg/kg (for i.v.); 10 mg/kg (for p.o.).

Administration:

Intravenous injection or oral gavage; single.

Result:

1.19 Pharmacokinetic Parameters of TK-129 in Male SD Rats.

	PO (10 mg/kg)	IV (2 mg/kg)
CL (L/h/kg)	9.9	4.2
V_ss (L/kg)	33.4	2.7
T_1/2 (h)	2.4	0.4
T_max (h)	0.4	-
C_max (ng/mL)	709.7	1229.1
AUC_0-24 (ng/mL•h)	1038.2	479.6
F (%)	42.37	-

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Wild C57BL/6 mice (8 to 10-week-old; half male and half female).
Dosage:	2 g/kg
Administration:	Oral gavage, single.
Result:	Exhibited all mice in the acute toxicity group survived and gained weight normally, after 2 weeks.

Animal Model:	C57BL/6 mice (isoproterenol (ISO)-induced).
Dosage:	50 mg/kg
Administration:	Oral gavage, twice daily for 24 days.
Result:	Alleviated myocardial remodeling induced by ISO in vivo.

Animal Model:

Male SD Rats (223.5-265.1 g).

Dosage:

2 mg/kg (for i.v.); 10 mg/kg (for p.o.).

Administration:

Intravenous injection or oral gavage; single.

Result:

1.19 Pharmacokinetic Parameters of TK-129 in Male SD Rats.

	PO (10 mg/kg)	IV (2 mg/kg)
CL (L/h/kg)	9.9	4.2
V_ss (L/kg)	33.4	2.7
T_1/2 (h)	2.4	0.4
T_max (h)	0.4	-
C_max (ng/mL)	709.7	1229.1
AUC_0-24 (ng/mL•h)	1038.2	479.6
F (%)	42.37	-

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Wild C57BL/6 mice (8 to 10-week-old; half male and half female).
Dosage:	2 g/kg
Administration:	Oral gavage, single.
Result:	Exhibited all mice in the acute toxicity group survived and gained weight normally, after 2 weeks.

Animal Model:	C57BL/6 mice (isoproterenol (ISO)-induced).
Dosage:	50 mg/kg
Administration:	Oral gavage, twice daily for 24 days.
Result:	Alleviated myocardial remodeling induced by ISO in vivo.

Animal Model:

Male SD Rats (223.5-265.1 g).

Dosage:

2 mg/kg (for i.v.); 10 mg/kg (for p.o.).

Administration:

Intravenous injection or oral gavage; single.

Result:

1.19 Pharmacokinetic Parameters of TK-129 in Male SD Rats.

	PO (10 mg/kg)	IV (2 mg/kg)
CL (L/h/kg)	9.9	4.2
V_ss (L/kg)	33.4	2.7
T_1/2 (h)	2.4	0.4
T_max (h)	0.4	-
C_max (ng/mL)	709.7	1229.1
AUC_0-24 (ng/mL•h)	1038.2	479.6
F (%)	42.37	-

性状

Solid

溶解性数据

In Vitro:

DMSO : 100 mg/mL (327.46 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	3.2746 mL	16.3730 mL	32.7461 mL
5 mM	0.6549 mL	3.2746 mL	6.5492 mL
10 mM	0.3275 mL	1.6373 mL	3.2746 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (8.19 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (8.19 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (8.19 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (8.19 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (8.19 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (8.19 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。