Ralinepag (APD811)
(Synonyms: APD811) 目录号 : GC32476
An IP receptor agonist
Cas No.:1187856-49-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ralinepag is a prostaglandin I2 (PGI2) receptor (IP) agonist (Ki = 3 nM).1 It is selective for IP over the PGD2 receptor (DP1) and the PGE2 receptor subtypes EP1-4 (Kis = 2,600, 9,600, 611, 143, and 678 nM, respectively, in radioligand binding assays). Ralinepag induces cAMP accumulation in CHO-K1 cells expressing human recombinant IP (EC50 = 8.5 nM). In vivo, ralinepag (30 mg/kg) prevents increases in pulmonary arterial pressure and vessel wall thickness in a rat model of monocrotaline-induced pulmonary arterial hypertension.
1.Tran, T.-A., Kramer, B., Shin, Y.-J., et al.Discovery of 2-(((1r,4r)-4-(((4-chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralingepag): An orally active prostacyclin receptor agonist for the treatment of pulmonary arterial hypertensionJ. Med. Chem.60(3)913-927(2017)
| Cas No. | 1187856-49-0 | SDF | |
| 别名 | APD811 | ||
| Canonical SMILES | O=C(O)COC[C@H]1CC[C@H](COC(N(C2=CC=C(Cl)C=C2)C3=CC=CC=C3)=O)CC1 | ||
| 分子式 | C23H26ClNO5 | 分子量 | 431.91 |
| 溶解度 | DMSO : 125 mg/mL (289.41 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。 |
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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 | 2.3153 mL | 11.5765 mL | 23.153 mL |
| 5 mM | 0.4631 mL | 2.3153 mL | 4.6306 mL |
| 10 mM | 0.2315 mL | 1.1576 mL | 2.3153 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。
Safety, tolerability, and pharmacokinetics of the selective prostacyclin receptor agonist ralinepag in single and multiple dosing studies of an immediate-release oral formulation in healthy volunteers
Pulm Circ 2020 May 14;10(2):2045894020922814.PMID:32489643DOI:PMC7238799
Ralinepag (APD811), an oral, potent, and selective prostacyclin receptor (IP) agonist is being developed for treatment of pulmonary arterial hypertension. Two, single-center, randomized, double-blind, placebo-controlled, Phase 1 studies (single ascending dose and multiple ascending dose) evaluated an oral immediate-release capsule formulation of ralinepag in healthy subjects. Blood samples assessed plasma pharmacokinetics and safety and tolerability data monitored adverse events, vital signs, laboratory findings, physical examination, and electrocardiograms. Eighty-two healthy subjects (single ascending dose (n = 32) and multiple ascending dose (n = 50)) completed the studies. No clinically significant safety issues were observed, except one serious adverse event of atrial fibrillation considered moderate in intensity. In the single ascending dose study, ralinepag was tolerated up to 100 µg (single dose), but not 200 µg due to nausea and vomiting. Dose proportional mean ralinepag plasma exposure measures were observed. Maximum plasma concentrations were reached within 1.0-1.5 h post-dose and mean terminal elimination half-life values from 20.5-26.4 h. In the multiple ascending dose study, ralinepag tolerability decreased with increasing QD or BID dose. Dose proportional steady-state plasma exposure measures were observed where evaluable, with mean steady-state peak-to-trough ratios ranging from 3.34-4.49 (QD dosing) and 1.95-2.36 (BID dosing). Mean effective half-life values ranged from 17.5-18.4 h, reflecting ∼1.7-fold (QD dosing) and ∼2.6-fold (BID dosing) accumulation in plasma exposure. Safety and tolerability of oral immediate-release ralinepag was generally consistent with expectations for this drug class, but more individualized dose escalation appears warranted. Ralinepag exhibited favorable pharmacokinetic properties, with BID dosing producing desired minimal steady-state peak-to-trough fluctuation. Overall, results supported further clinical investigation of ralinepag and guided development of an extended-release formulation to facilitate QD dosing.