ASP6432
目录号 : GC35409
ASP6432 是一种有效选择性的 1 型溶血磷脂酸受体 (LPA1) 拮抗剂， 在人 LPA1 和大鼠 LPA1 的 IC50 值分别为 11 nM 和 30 nM。
Cas No.:1282549-08-9
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ASP6432 is a potent and selective type 1 lysophosphatidic acid receptor (LPA1) antagonist with IC50s of 11 nM and 30 nM for human LPA1 and rat LPA1, respectively[1]. IC50: 11 nM (human LPA1), 30 nM (rat LPA1)[1]
ASP6432 inhibits the LPA-induced proliferation of human prostate stromal cells[1].
[1]. Sakamoto K, et al. Effect of ASP6432, a Novel Type 1 Lysophosphatidic Acid Receptor Antagonist, on Urethral Function and Prostate Cell Proliferation. J Pharmacol Exp Ther. 2018 Aug;366(2):390-396.
| Cas No. | 1282549-08-9 | SDF | |
| Canonical SMILES | O=C(C1=CSC(CN(C(C2=CC(OC)=C(C)C(OC)=C2)=O)CCCC3=CC=CC=C3)=N1)[N-]S(=O)(NCC)=O.[K+] | ||
| 分子式 | C26H31KN4O6S2 | 分子量 | 598.78 |
| 溶解度 | DMSO: 250 mg/mL (417.52 mM) | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6701 mL | 8.3503 mL | 16.7006 mL |
| 5 mM | 0.334 mL | 1.6701 mL | 3.3401 mL |
| 10 mM | 0.167 mL | 0.835 mL | 1.6701 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。
ASP6432, a type 1 lysophosphatidic acid receptor antagonist, reduces urethral function during urine voiding and improves voiding dysfunction
Eur J Pharmacol 2019 Mar 15;847:83-90.PMID:30658116DOI:10.1016/j.ejphar.2019.01.014.
Current pharmacotherapies for voiding dysfunctions are in need of improvement. Lysophosphatidic acid (LPA) is a phospholipid that contracts the urethra by activating type 1 LPA receptors (LPA1). However, the role of LPA1 in regulating urethral tonus during urine voiding which primarily affects the voiding function has not been investigated. To elucidate the role of LPA1 in the regulation of urethral tonus during urine voiding, we investigated the effects of ASP6432, a novel LPA1 antagonist, and the α1-adrenoceptor antagonist tamsulosin on urethral perfusion pressure (UPP) at the filling phase (UPPbase) and the minimum UPP at the voiding phase (UPPnadir) in anesthetized rats under isovolumetric conditions. We further evaluated the effects of ASP6432 and tamsulosin on voiding dysfunction characterized by changes in post-void residual urine (PVR) and voiding efficiency (VE) induced by the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) in conscious rats using single cystometry. ASP6432 dose-dependently decreased UPPbase and UPPnadir, while tamsulosin reduced UPPbase but did not change UPPnadir. ASP6432 dose-dependently suppressed the L-NAME-induced increase in PVR and decrease in VE, whereas tamsulosin did not affect either PVR or VE. We demonstrate that ASP6432 reduced UPPnadir and ameliorated L-NAME-induced voiding dysfunction, neither of which were affected by tamsulosin. Our study results suggest that LPA1 has a significant role in regulating urethral tonus during urine voiding, and highlight the potential of ASP6432 for improving voiding dysfunctions associated with various lower urinary tract diseases.
Effect of ASP6432, a Novel Type 1 Lysophosphatidic Acid Receptor Antagonist, on Urethral Function and Prostate Cell Proliferation
J Pharmacol Exp Ther 2018 Aug;366(2):390-396.PMID:29884626DOI:10.1124/jpet.118.247908.
Current pharmacotherapies for lower urinary tract symptoms associated with benign prostate hyperplasia (LUTS/BPH) are in need of improvement. Lysophosphatidic acid (LPA) is a phospholipid with various biologic functions. However, its exact role in the lower urinary tract and its target receptor subtype have not been fully elucidated. We investigated the role of LPA and the type 1 LPA receptor (LPA1) in urethral/prostatic contractile function and prostate cell proliferation by pharmacologically characterizing ASP6432 (potassium 1-(2-{[3,5-dimethoxy-4-methyl-N-(3-phenylpropyl)benzamido]methyl}-1,3-thiazole-4-carbonyl)-3-ethyl-2,2-dioxo-2λ6-diazathian-1-ide), a novel LPA1 antagonist. ASP6432 exhibited potent and selective antagonistic activity against LPA1 in cells expressing LPA receptor subtypes. In isolated rat tissue strips and anesthetized rats, ASP6432 concentration-/dose-dependently inhibited LPA-induced urethra and prostate contractions. In addition, in anesthetized rats, ASP6432 maximally decreased the urethral perfusion pressure (UPP) in the absence of exogenous LPA stimulation by 43% from baseline, whereas tamsulosin, an α1-adrenoceptor antagonist, reduced UPP by 22%. Further, in human prostate stromal cells, ASP6432 significantly and concentration-dependently suppressed LPA-induced bromodeoxyuridine incorporation. These results demonstrate a pivotal role for LPA and LPA1 in the regulation of urethral tonus and prostate cell proliferation. The potent urethral relaxation and inhibition of prostatic stromal cell growth indicate the potential of ASP6432 as a novel therapeutic agent for LUTS/BPH.
Modulation of urinary frequency via type 1 lysophosphatidic acid receptors: Effect of the novel antagonist ASP6432 in conscious rats
Eur J Pharmacol 2019 Jun 15;853:11-17.PMID:30853531DOI:10.1016/j.ejphar.2019.03.011.
Bladder dysfunctions associated with benign prostatic hyperplasia are not sufficiently alleviated by current pharmacotherapies. Lysophosphatidic acid (LPA) is a phospholipid with diverse biological effects. LPA modulates prostate and urethral contraction via the type 1 LPA (LPA1) receptor, suggesting the potential of the LPA1 receptor as a therapeutic target. However, the role of LPA and the LPA1 receptor in bladder function has not been studied in vivo. We investigated the effects of LPA and the novel LPA1 receptor antagonist ASP6432 (potassium 1-(2-{[3,5-dimethoxy-4-methyl-N-(3-phenylpropyl)benzamido]methyl}- 1,3-thiazole-4-carbonyl)- 3-ethyl-2,2-dioxo-2λ6-diazathian-1-ide) on the micturition reflex in conscious rats using cystometry. Intravenous infusion of LPA decreased the micturition interval and threshold pressure with no apparent changes in baseline pressure or maximum intravesical pressure. ASP6432 inhibited the LPA-induced decrease in MI. In contrast, ASP6432 had no effect on the LPA-induced decrease in threshold pressure. Similarly, ASP6432 had no effect on either baseline pressure or maximum intravesical pressure. We also evaluated the effect of ASP6432 on the urinary frequency induced by the nitric oxide synthase inhibitor L-Nω-nitro arginine methyl ester (L-NAME). Intravenous L-NAME administration decreased the micturition interval. ASP6432 dose-dependently reversed the L-NAME-induced decrease in micturition interval. Our findings demonstrate for the first time that LPA causes bladder overactivity in rats. ASP6432 inhibited the LPA- and L-NAME-induced decrease in micturition interval, suggesting a significant role for the LPA1 receptor in regulating the functional capacity of the bladder. Our results also suggest the potential of ASP6432 as a novel therapy for the treatment of bladder dysfunction associated with lower urinary tract diseases.