Tadalafil
(Synonyms: 他达那非; IC-351) 目录号 : GC17074
Tadalafil是一种有效、可逆且具有选择性的磷酸二酯酶5（PDE5）小分子抑制剂，IC50为1.8nM。Tadalafil还能够抑制PDE11（IC50为11nM）。
Cas No.:171596-29-5
Sample solution is provided at 25 µL, 10mM.
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Tadalafil is an effective, reversible and selective small molecule inhibitor of phosphodiesterase 5 (PDE5) with an IC50 of 1.8nM. Tadalafil can also inhibit PDE11 (IC50 of 11nM) [1-2]. PDE is a key protein that regulates intracellular cyclic nucleotide turnover and smooth muscle tension [3]. Tadalafil can be used to treat erectile dysfunction and improve pulmonary arterial hypertension [4].
In vitro, different concentrations of Tadalafil (0.2, 0.1, 0.05 and 0.025μg/ml; 0.5ml; 2h) were applied to semen samples collected from normal human sperm groups and weak sperm groups. At a concentration of 0.025μg/ml, sperm motility significantly increased [5]. Tadalafil (1, 3 and 10μM; 48h) increased the expression of CYP3A protein in human liver cells, while the CYP3A activity did not increase accordingly [6].
In vivo, Tadalafil (0.09mg/200g body weight/day; gavage; 2 months) significantly improved erectile function in streptozotocin-induced diabetic rats, increased the percentage of smooth muscle and elastic tissue area, and significantly reduced fibrous tissue [7]. Tadalafil (1mg/kg/day; 4 weeks; i.p.) treatment alleviated cardiac hypertrophy and pulmonary edema in mice with myocardial infarction (MI), reduced the area of fibrosis and decreased cell apoptosis [8].
References:
[1] Blount MA, Beasley A, Zoraghi R, et al. Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol. 2004;66(1):144-152.
[2] Card, G.L., England, B.P., Suzuki, Y., et al. Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure 12(12), 2233-2247 (2004).
[3] Gratzke C, Ückert S, Kedia G, et al. In vitro effects of PDE5 inhibitors sildenafil, vardenafil and tadalafil on isolated human ureteral smooth muscle: a basic research approach[J]. Urological research, 2007, 35(1): 49-54.
[4] Coward R M, Carson C C. Tadalafil in the treatment of erectile dysfunction[J]. Therapeutics and clinical risk management, 2008, 4(6): 1315-1330.
[5] Yang Y, Ma Y, Yang H, et al. Effect of acute tadalafil on sperm motility and acrosome reaction: in vitro and in vivo studies. Andrologia. 2014;46(4):417-422.
[6] Ring B J, Patterson B E, Mitchell M I, et al. Effect of tadalafil on cytochrome P450 3A4–mediated clearance: studies in vitro and in vivo[J]. Clinical pharmacology & therapeutics, 2005, 77(1): 63-75.
[7] Blount MA, Beasley A, Zoraghi R, et al. Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol. 2004;66(1):144-152.
[8] Salloum F N, Chau V Q, Hoke N N, et al. Tadalafil prevents acute heart failure with reduced ejection fraction in mice[J]. Cardiovascular drugs and therapy, 2014, 28(6): 493-500.
Tadalafil是一种有效、可逆且具有选择性的磷酸二酯酶5（PDE5）小分子抑制剂，IC50为1.8nM。Tadalafil还能够抑制PDE11（IC50为11nM）[1-2]。PDE是调节细胞内环核苷酸周转和平滑肌张力的关键蛋白质 [3]。Tadalafil可用于治疗勃起功能障碍和改善肺动脉高压 [4]。
在体外，不同浓度的Tadalafil（0.2、0.1、0.05和0.025μg/ml; 0.5ml; 2h）处理人正常精子组和弱精子组收集的精液样品，在0.025μg/ml浓度下精子活力显著增加 [5]。Tadalafil（1、3和10μM; 48h）增加了在人肝细胞中CYP3A蛋白的表达，而CYP3A活性没有相应增加 [6]。
在体内，Tadalafil（0.09mg/200g weight/d; gavage; 2 months）显著改善链脲佐菌素诱导的糖尿病大鼠的勃起功能，增加了平滑肌和弹性组织的面积百分比，并显著减少纤维组织 [7]。Tadalafil（1mg/kg/day; 4 weeks; i.p.）治疗减轻了心肌梗死（MI）小鼠的心脏肥大和肺水肿，减少了纤维化面积以及细胞凋亡 [8]。
| Cell experiment [1]: | |
Cell lines | Hepatocyte |
Preparation Method | The liver cell monolayers cultured in 6-well plates (approximately 100 million cells per well) were incubated in triplicate with Tadalafil (1, 3 or 10μM), solvent control (0.1% dimethyl sulfoxide), or known inducers (1μg/ml 3-methylcholanthrene or 10μM rifampicin) in HMM for 48 hours. The culture medium was removed, and the cells were rinsed with HMM. Then, the cells were incubated with midazolam (10μM) or 7-ethoxyrosanidin red (2μM) in HMM containing 3mM salicylamide for 30 minutes. The cells were collected, and the content of CYP3A4 immunoreactive protein in the liver cell cultures was determined by Western blot analysis. |
Reaction Conditions | 1, 3 and 10μM; 48h |
Applications | Tadalafil significantly increased the expression of CYP3A protein in human liver cell. |
| Animal experiment [2]: | |
Animal models | Albino rats |
Preparation Method | The rats were divided into 4 groups: group 1, (n = 8), controls that received nothing; group 2 (n = 8), sham control rats that received 1mL peanut oil daily by gastric gavage; group 3 (n = 16) induced diabetic rats; and group 4 (n = 16), induced diabetic rats that received 0.09mg/200g weight Tadalafil daily, equivalent to 5mg for humans, for 2 months by gastric gavage mixed with 1mL peanut oil. The rats were euthanized a day after the last dose of Tadalafil, intracavernosal pressure (ICP) and mean arterial pressure (MAP) were estimated, and rats were carefully dissected. A small fragment (2mm2) from the middle of the shaft of the penis was selected for electron microscopy (EM). The rest was fixed in fresh 2% formaldehyde in 0.1M phosphate buffer (pH 7.4), dehydrated, and embedded in paraffin. Sections of 5μm thickness were cut and subjected to hematoxylin and eosin, orcein, and Masson trichrome stains to be examined by light microscopy. |
Dosage form | 0.09mg/200g body weight per day for 2 months; gavage |
Applications | Tadalafil significantly improved the erectile function of streptozotocin-induced diabetic rats, increased the percentage of smooth muscle and elastic tissue area, and significantly reduced fibrous tissue. |
References: | |
| Cas No. | 171596-29-5 | SDF | |
| 别名 | 他达那非; IC-351 | ||
| 化学名 | (6R,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-methyl-2,3,12,12a-tetrahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4(6H,7H)-dione | ||
| Canonical SMILES | O=C1N(C)CC(N([C@@H]2C(C=C3)=CC4=C3OCO4)[C@]1([H])CC5=C2NC6=CC=CC=C56)=O | ||
| 分子式 | C22H19N3O4 | 分子量 | 389.4 |
| 溶解度 | ≥ 16.6 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5681 mL | 12.8403 mL | 25.6805 mL |
| 5 mM | 513.6 μL | 2.5681 mL | 5.1361 mL |
| 10 mM | 256.8 μL | 1.284 mL | 2.5681 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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