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 activehistamineH3receptorantagonist, with anIC50of 1.7 nM for human H3[1]. |
| IC50& Target | human H3receptor 1.7 nM (IC50) | rhesus H3receptor 4.3 nM (Ki) | human H3receptor 6.8 nM (Ki) | rat H3receptor 33 nM (Ki) |
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体外研究
(In Vitro) | 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[1].
MK-0249 displays potent binding affinity to human, rat, and rhesus H3receptors with Kivalues of 6.8 ± 1.3 nM, 33 ± 3 nM, and 4.3 ± 1.2 nM, respectively[1].
MK-0249 shows high intrinsic activity[1].
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体内研究
(In Vivo) | MK-0249 (Compound 1) (0-30 mg/kg; p.o.; once) elevates histamine levels in the rat brain in a dose-dependent manner[1].
MK-0249 (10 mg/kg; p.o.; once) shows markedly higher brain penetrability and a lower plasma Occ90 value inmdr1a(-/-) mice than inmdr1a(+/+) mice[1].
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[1].
| Animal Model: | SD rats[1] | | 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-deficientmdr1a(-/-) and wild typemdr1a(+/+) CF-1 mice[1] | | Dosage: | 10 mg/kg | | Administration: | Oral administration, once | | Result: | The brain-to-plasma ratio inmdr1a(-/-) mice (b/p = 14) was remarkably higher than that in SD rats (b/p = 1.1) andmdr1a(+/+) mice (b/p = 0.8). |
| Animal Model: | Male Sprague-Dawley rats, male Beagle dogs, and male rhesus monkeys[1] | | Dosage: | 1 or 3 mg/kg | | Administration: | IV or PO (Pharmacokinetic Analysis) | | Result: | Pharmacokinetic Parameters of 1 in Rats, Dogs, and Rhesus Monkeysa[1]
| | iv (1 mg/kg) | | | | po (3 mg/kg) | | | CLp
(mL/min/kg) | Vdss
(L/kg) | t1/2
(h) | | Cmax
(μM) | AUC0-∞
(μM h) | Fb
(%) | | rat | 12 | 4.4 | 5.5 | | 1.01 | 6.35 | 65 | | dog | 19 | 9.7 | 9.9 | | 1.8 | 11.8 | >100 | | 862309-06-6 | | 运输条件 | Room temperature in continental US; may vary elsewhere. | | 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
| | 溶解性数据 | In Vitro: DMSO : 50 mg/mL(115.89 mM;Need ultrasonic) 配制储备液 | 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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin 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 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 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。 *以上所有助溶剂都可在本网站选购。
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