Desethyl KBT-3022
目录号 : GC32663
DesethylKBT-3022是新型抗血小板药物KBT-3022的主要活性代谢物。
Cas No.:101001-72-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Desethyl KBT-3022 is the main active metabolite of the new antiplatelet agent, KBT-3022.
Pretreatment with desethyl KBT-3022 0.1, 0.3 and 1 mg/kg, i.v. prolongs the time required to achieve thrombotic occlusion in the femoral artery and inhibits collagen-induced platelet aggregation in whole blood ex vivo, each in a dose-dependent manner. Desethyl KBT-3022 inhibits the thrombin-induced aggregation of washed platelets in a concentration-dependent manner 1-40 μM[1].
[1]. Shimazawa M, et al. Antithrombotic effects in a rat model of aspirin-insensitive arterial thrombosis of desethyl KBT-3022, the main active metabolite of a new antiplatelet agent, KBT-3022. Eur J Pharmacol. 1997 Jun 11;328(2-3):183-9.
| Cas No. | 101001-72-3 | SDF | |
| Canonical SMILES | O=C(O)CN1C(C2=NC(C3=CC=C(OC)C=C3)=C(C4=CC=C(OC)C=C4)S2)=CC=C1 | ||
| 分子式 | C23H20N2O4S | 分子量 | 420.48 |
| 溶解度 | Soluble 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3782 mL | 11.8912 mL | 23.7823 mL |
| 5 mM | 0.4756 mL | 2.3782 mL | 4.7565 mL |
| 10 mM | 0.2378 mL | 1.1891 mL | 2.3782 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The mechanism of action of KBT-3022, a new antiplatelet agent
Gen Pharmacol 1997 Feb;28(2):229-35.PMID:9013200DOI:10.1016/s0306-3623(96)00190-5.
1. The mechanism of action of a new antiplatelet agent, KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and its active main metabolite, Desethyl KBT-3022, was investigated. 2. KBT-3022 and Desethyl KBT-3022 inhibited cyclooxygenase from ovine seminal gland with IC50 values of 0.69 and 0.43 microM, respectively. 3. At concentrations higher than those required for cyclooxygenase inhibition, Desethyl KBT-3022 inhibited cAMP-phosphodiesterase, specific binding of U46619, and release of phosphatidic acid from thrombin-stimulated platelets. 4. Oral administration of KBT-3022 inhibited the production of thromboxane B2 during blood coagulation more potently than the production of 6-keto-prostaglandin F1 alpha from aortic strips in guinea pigs. 5. These findings suggest that KBT-3022 may inhibit platelet activation principally via the inhibition of cyclooxygenase by Desethyl KBT-3022.
[Determination of the main metabolite (Desethyl KBT-3022) of a new antiplatelet agent, KBT-3022 in plasma by gas chromatography]
Yakugaku Zasshi 1992 Jun;112(6):414-7.PMID:1432594DOI:10.1248/yakushi1947.112.6_414.
A highly sensitive, accurate and reproducible gas chromatographic method for the determination of a main metabolite, 2-[4,5-bis(4-methoxy-phenyl)thiazol-2-yl] pyrrol-ylacetic acid (Desethyl KBT-3022) of a new antiplatelet agent, ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate (KBT-3022), in the human or dog plasma has been developed. Desethyl KBT-3022 in the plasma was extracted with a mixture of n-hexane and dichloromethane (1:1), and was derivatized using pentafluorobenzyl bromide. The obtained pentafluorobenzyl derivative of Desethyl KBT-3022 in the plasma was separated by high-performance liquid chromatography. After the separation, the pentafluorobenzyl derivative of Desethyl KBT-3022 was detected by gas chromatography. Gas chromatography was performed with a Ultra 1 column (12 m x 0.22 mm i.d., film thickness 0.33 microns), using an electron capture detector. 2-[2-(4,5-Bis(4-methoxyphenyl)thiazol-2-yl)pyrrol-l-yl]propionic acid was used as an internal standard. The detection limit of Desethyl KBT-3022 in the plasma was 0.2 ng/ml. The coefficients of variation were below 5.3%. This method was applied to the determination of the plasma concentration of Desethyl KBT-3022 after oral administration of KBT-3022 to dogs.
Effect of KBT-3022, a new diphenylthiazole derivative, on platelet functions
J Pharm Pharmacol 1995 Sep;47(9):768-74.PMID:8583391DOI:10.1111/j.2042-7158.1995.tb06739.x.
The effects of KBT-3022 and its metabolite Desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo. KBT-3022 and Desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid. Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid. These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.
Antithrombotic effects in a rat model of aspirin-insensitive arterial thrombosis of Desethyl KBT-3022, the main active metabolite of a new antiplatelet agent, KBT-3022
Eur J Pharmacol 1997 Jun 11;328(2-3):183-9.PMID:9218700DOI:10.1016/s0014-2999(97)83044-0.
The antithrombotic effect of Desethyl KBT-3022, which is the main active metabolite of the new antiplatelet agent, KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl] pyrrol-1-ylacetate; a cyclooxygenase inhibitor), was determined using a photochemically induced arterial thrombosis model in the rat femoral artery. Pretreatment with Desethyl KBT-3022 (0.1, 0.3 and 1 mg/kg, i.v.) prolonged the time required to achieve thrombotic occlusion in the femoral artery and inhibited collagen-induced platelet aggregation in whole blood ex vivo, each in a dose-dependent manner. In all 6 rats used, particularly at the highest dose (1 mg/kg, i.v.) tested, cyclic variations in blood flow were hardly ever observed and complete cessation of blood flow did not occur during the 30-min observation time. BM-13505 (1, 3 and 10 mg/kg, i.v.), a thromboxane A2 receptor antagonist, also prolonged the time to occlusion, but cyclic variations in blood flow did occur. On the other hand, aspirin (10 and 30 mg/kg, i.v.) had little effect in terms of preventing thrombosis, although it inhibited collagen-induced platelet aggregation to the same extent as did Desethyl KBT-3022. Desethyl KBT-3022 inhibited the thrombin-induced aggregation of washed platelets in a concentration-dependent manner (1-40 microM), whereas aspirin and BM-13505 did not. These findings suggest that the potent antithrombotic effect of Desethyl KBT-3022 may be attributable in part to its additional ability to inhibit thrombin-induced platelet aggregation. Accordingly, thromboxane A2 and thrombin may be important thrombotic mediators in this rat model.
Inhibitory effects of the new anti-platelet agent KBT-3022 and its metabolite on rabbit neutrophil function in vitro
Jpn J Pharmacol 1996 Apr;70(4):291-302.PMID:8847836DOI:10.1254/jjp.70.291.
The effects of the new anti-platelet agent KBT-3022, ethyl 2-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate, and its metabolite Desethyl KBT-3022 on rabbit neutrophil function were investigated in comparison with the effects of acetylsalicylic acid (ASA), ticlopidine hydrochloride (TP), cilostazol (CIL) and indomethacin (IM). The adhesion and migration of neutrophils induced by formyl-methionyl-leucyl-phenylalanine (fMLP) were inhibited by all the compounds tested, their rank order of potency being KBT-3022 = Desethyl KBT-3022 > TP = CIL = IM > ASA. KBT-3022, Desethyl KBT-3022, CIL and IM all suppressed fMLP-induced increases in the intracellular free Ca2+ concentration ([Ca2+]i) in neutrophils, their potencies correlating with their inhibitory effects on fMLP-induced adhesion and migration. KBT-3022 (1 microM), Desethyl KBT-3022 (1-10 microM) and CIL (10 microM) but not IM significantly inhibited both neutrophil migration and the increase in [Ca2+]i induced by leukotriene B4 (LTB4). KBT-3022 (1 microM) and Desethyl KBT-3022 (1 microM) suppressed the increase in [Ca2+]i induced by complement C5a. Although KBT-3022 and Desethyl KBT-3022 did not influence [3H]LTB4 and [125I]C5a specific binding, [3H]fMLP specific binding was inhibited by Desethyl KBT-3022 (IC50: 1.9 microM). Neutrophil adhesion and superoxide anion production stimulated by phorbol 12-myristate 13-acetate were partially inhibited by KBT-3022 (1 microM) and Desethyl KBT-3022 (1-10 microM). These results suggest that KBT-3022 and Desethyl KBT-3022 have a wider spectrum of action and are more potent inhibitors of neutrophil activation than ASA, TP, CIL and IM.