MK-0249|cas:862309-06-6|西域试剂

MK-0249,99.50%

产品编号：Bellancom-U00076| CAS NO：862309-06-6| 分子式：C₂₃H₂₄F₃N₃O₂| 分子量：431.45

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	包装	价格	库存与货期	购买量	操作
Bellancom-U00076		￥5800.00	杭州北京（现货）
Bellancom-U00076		￥19500.00	杭州北京（现货）

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MK-0249

产品介绍

MK-0249 (Compound 1) 是一种有效的、选择性的、具有口服活性的 histamine H₃ 受体拮抗剂，对人体H₃ 受体的IC₅₀ 值为 1.7 nM。

生物活性

MK-0249 (Compound 1) is a potent, selective and orally active histamine H₃ receptor antagonist, with an IC₅₀ of 1.7 nM for human H3.

体外研究

MK-0249 (Compound 1) shows very good hepatic clearance values (CLh e 11 mL/min/kg), and is a substrate for rat P-gp but not for human P-gp.
MK-0249 displays potent binding affinity to human, rat, and rhesus H₃ receptors with K_i values of 6.8 ± 1.3 nM, 33 ± 3 nM, and 4.3 ± 1.2 nM, respectively.
MK-0249 shows high intrinsic activity.

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

体内研究

MK-0249 (Compound 1) (0-30 mg/kg; p.o.; once) elevates histamine levels in the rat brain in a dose-dependent manner.
MK-0249 (10 mg/kg; p.o.; once) shows markedly higher brain penetrability and a lower plasma Occ90 value in mdr1a (-/-) mice than in mdr1a (+/+) mice.
MK-0249 shows rodent brain permeability and is significantly limited by P-gp mediated efflux in rodents, whereas the extent of P-gp mediated efflux in humans should be very small or negligible.

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

Animal Model:	SD rats
Dosage:	3, 10 and 30 mg/kg
Administration:	Oral administration, once
Result:	Showed a statistically significant increase in tele-methylhistamine levels at 30 mg/kg.

Animal Model:	P-gp-deficient mdr1a (-/-) and wild type mdr1a (+/+) CF-1 mice
Dosage:	10 mg/kg
Administration:	Oral administration, once
Result:	The brain-to-plasma ratio in mdr1a (-/-) mice (b/p = 14) was remarkably higher than that in SD rats (b/p = 1.1) and mdr1a (+/+) mice (b/p = 0.8).

Animal Model:

Male Sprague-Dawley rats, male Beagle dogs, and male rhesus monkeys

Dosage:

1 or 3 mg/kg

Administration:

IV or PO (Pharmacokinetic Analysis)

Result:

Pharmacokinetic Parameters of 1 in Rats, Dogs, and Rhesus Monkeys^a

iv (1 mg/kg)

po (3 mg/kg)

CL_p
(mL/min/kg)

V_dss
(L/kg)

t_1/2
(h)

C_max
(µM)

AUC_0-∞
(µM h)

F^b
(%)

rat

4.4

5.5

1.01

6.35

dog

9.7

9.9

1.8

11.8

>100

体内研究

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

Animal Model:	SD rats
Dosage:	3, 10 and 30 mg/kg
Administration:	Oral administration, once
Result:	Showed a statistically significant increase in tele-methylhistamine levels at 30 mg/kg.

Animal Model:	P-gp-deficient mdr1a (-/-) and wild type mdr1a (+/+) CF-1 mice
Dosage:	10 mg/kg
Administration:	Oral administration, once
Result:	The brain-to-plasma ratio in mdr1a (-/-) mice (b/p = 14) was remarkably higher than that in SD rats (b/p = 1.1) and mdr1a (+/+) mice (b/p = 0.8).

Animal Model:

Male Sprague-Dawley rats, male Beagle dogs, and male rhesus monkeys

Dosage:

1 or 3 mg/kg

Administration:

IV or PO (Pharmacokinetic Analysis)

Result:

Pharmacokinetic Parameters of 1 in Rats, Dogs, and Rhesus Monkeys^a

iv (1 mg/kg)

po (3 mg/kg)

CL_p
(mL/min/kg)

V_dss
(L/kg)

t_1/2
(h)

C_max
(µM)

AUC_0-∞
(µM h)

F^b
(%)

rat

4.4

5.5

1.01

6.35

dog

9.7

9.9

1.8

11.8

>100

性状

Solid

溶解性数据

In Vitro:

DMSO : 50 mg/mL (115.89 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.3178 mL	11.5888 mL	23.1777 mL
5 mM	0.4636 mL	2.3178 mL	4.6355 mL
10 mM	0.2318 mL	1.1589 mL	2.3178 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: ≥ 1.25 mg/mL (2.90 mM); Clear solution

此方案可获得 ≥ 1.25 mg/mL (2.90 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 12.5 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: ≥ 1.25 mg/mL (2.90 mM); Clear solution

此方案可获得 ≥ 1.25 mg/mL (2.90 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 12.5 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: ≥ 1.25 mg/mL (2.90 mM); Clear solution

此方案可获得 ≥ 1.25 mg/mL (2.90 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 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。