Cipemastat is a potent, competitive inhibitor of human collagenases 1, 2 and 3 with K_is of 3.0, 4.4 and 3.4 nM, respectively.

Cipemastat (Ro 32-3555) is a potent, competitive inhibitor of human matrix metalloproteinases. Cipemastat is selective for collagenase 1, 2 and 3 relative to related matrix metalloproteinases. Cipemastat is also a potent inhibitor of rat collagenase (IC₅₀=44.7±3.4 nM (n=4)). In vitro cartilage degradation ± inhibited IL-1a induced cartilage degradation in vitro in a concentration-dependent manner with an IC₅₀=60 nM. The inhibition is not mediated by a cytotoxic action on explant chondrocytes. Cipemastat, at all concentrations tested, fail to modify glucose utilization when compared to explants cultured in the presence of IL-La alone^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

The amount of hydroxyproline in non-implanted cartilage is 119.3±4.2 nM/mg and this decreases in cartilages implanted in vehicle-dosed animals to 53.6±7.1 nM/mg over a fourteen day period. Animals administered Cipemastat orally at doses of 2.5, 5, 10 and 25 mg/kg show statistically increased levels of implanted cartilage hydroxypro-line. Fourteen days after the second challenge injection of P. acnes, the area of cartilage most consistently affected by pannus is the lateral femoral condyle, which is the area analysed. In non-arthritic animals the mean cartilage area is 0.17±0.02 mm² (n=5). In arthritic animals there is a significant decrease to a mean area of 0.086±0.01 mm² (n=10). The group of animals dosed with Cipemastat (50 mg/kg, p.o.) show a significantly greater area of cartilage with a mean value of 0.126±0.012 mm² (n=9). The pannus area in vehicle-dosed animals is 0.099±0.017 mm² and in Cipemastat dosed animals 0.102±0.019 mm². Adjuvant arthritis injection of adjuvant induced two phases of swelling of the injected paw in vehicle-dosed rats. The primary swelling phase occurred between days 0 to 5 and induced an increase in paw volume of 1.9±0.1 mL; the secondary phase occurrs between day 9 to 14 and there was an increase in paw swelling of 0.98±0.08 mL. The group of animals dosed with dexamethasone (0.1 mg/kg) shows a significant reduction in both primary (0.2±0.03 mL) and secondary inflammation (0.07±0.08 mL) paw swelling as well as total inhibition of the lesion score^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

436.55

C₂₂H₃₆N₄O₅

190648-49-8

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 100 mg/mL (229.07 mM; Need ultrasonic)

*

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 (5.73 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.73 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 (5.73 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.73 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 (5.73 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.73 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。

• [1]. E J Lewis, et al. Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo. Br J Pharmacol. 1997 May; 121(3): 540–546.

Rats^[1]
Cipemastat (Ro 32-3555) is formulated in 5% succinylated gelatin and the volume administered to rats is 10 mL/kg, p.o. Female, AHH/R strain rats are used. Rats are anaesthetized in an isoflurane-closed system, and an intra-articular injection of 20 mL of the P. acnes/Freund’s incomplete adjuvant emulsion made into the right hind knee. Twenty-eight days later the injection is repeated with the same volume and concentration of antigen to induce the monoarthritis. Animals are orally dosed once daily with either 5% succinylated gelatin as the control vehicle or Cipemastat (50 mg/kg) starting on day 1 after challenge injection. Groups of eight female AHH/R rats are used in these experiments. The animals are dosed twice daily with either 50, 25 or 10 mg/kg Cipemastat, dexamethasone (0.1 mg/kg, s.c. once/day) or vehicle control (10 mL/kg, p.o., b.i.d.). The arthritis is induced by injection into the right hind paws with 0.1 mL of a 5 mg/mL homogenized suspension of Mycobacterium tuberculosis in liquid paraffin. The volume of both the right and left hind paws is measured by water plethysmography by immersing the paw up to the hair line of the ankle. Paw volumes are determined every two or three days^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. E J Lewis, et al. Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo. Br J Pharmacol. 1997 May; 121(3): 540–546.