iJak-381
(Synonyms: iJak381; iJak 381; iJak-381; GDC-0214; GDC 0214; GDC0214;) 目录号 : GB62277iJAK-381是一种新型的小分子抑制剂，选择性靶向Janus激酶（JAK）家族，包括JAK1、JAK2、JAK3和TYK，在1mM ATP下IC50值分别为8.52、53.4、5998和240nM。
Cas No.:1831144-46-7
Sample solution is provided at 25 µL, 10mM.
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iJAK-381 is a novel, small-molecule inhibitor selectively targeting the Janus kinase (JAK) family, including JAK1, JAK2, JAK3 and TYK with IC50 values of 8.52, 53.4, 5998 and 240nM respectively at 1mM ATP[1]. In preclinical species, iJAK-381 is retained in the lung and is rapidly cleared in the circulation[2].
In vivo, iJak-381 (10.7mg/kg) administered via dry powder inhalation in Ovalbumin-induced asthma mice model reduced total BAL cells, eosinophils, and expression of IL-13-dependent genes also inhibited pSTAT6 and pSTAT3 induction[1]. Thin film freezing (TFF)-iJak-381 powders (0.5mg/kg) were delivered via intratracheal administration into each Sprague−Dawley rat with a single dose. Four formulations of TFF-iJak-381 were tested: F20 (80% iJak-381, 20% lactose), F21 (80% iJak-381, 20% leucine), F22 (80% iJak-381, 10% lactose, 10% leucine), and micronized iJak-381 blended with micronized leucine. The formulation F20, which contains 80% iJak-381 and 20% lactose, provided enhanced lung targeting with reduced systemic exposure compared to micronized iJak-381[3].
References:
[1] Dengler H S, X M, Peng I, et al. Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma. Sci Transl Med. 2018 Nov 21;10(468):eaao2151.
[2] Braithwaite I E, Cai F, Tom J A, et al. Inhaled JAK inhibitor GDC-0214 reduces exhaled nitric oxide in patients with mild asthma: A randomized, controlled, proof-of-activity trial. J Allergy Clin Immunol. 2021 Sep;148(3):783-789.
[3] Moon C, Sahakijpijarn S, Maier E Y, et al. Inhaled JAK Inhibitor GDC-0214 Nanoaggregate Powder Exhibits Improved Pharmacokinetic Profile in Rats Compared to the Micronized Form: Benefits of Thin Film Freezing. Mol Pharm. 2024 Feb 5;21(2):564-580.
iJAK-381是一种新型的小分子抑制剂，选择性靶向Janus激酶（JAK）家族，包括JAK1、JAK2、JAK3和TYK，在1mM ATP下IC50值分别为8.52、53.4、5998和240nM[1]。在临床前动物实验中，iJAK-381会在肺部留存，并在血液循环中被快速清除[2]。
在体内实验中，通过干粉吸入的方式给予卵清蛋白诱导的哮喘小鼠模型iJak-381（10.7mg/kg），可减少支气管肺泡灌洗液（BAL）中的总细胞数、嗜酸性粒细胞数量，并抑制IL-13依赖性基因的表达，同时还能抑制pSTAT6和pSTAT3的诱导[1]。将薄膜冷冻（TFF）-iJak-381粉末（0.5mg/kg）通过气管内给药的方式单次给予每只Sprague−Dawley大鼠。对四种TFF-iJak-381制剂进行了测试：F20（含80%的iJak-381和20%的乳糖）、F21（含80%的iJak-381和20%的亮氨酸）、F22（含80%的iJak-381、10%的乳糖和10%的亮氨酸）以及与微粉化亮氨酸混合的微粉化iJak-381。其中，含有80% iJak-381和20%乳糖的F20制剂相比微粉化iJak-381，具有更好的肺部靶向性，且全身暴露量更低[3]。
| Animal experiment [1]: | |
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Animal models |
Guinea pigs |
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Preparation Method |
Guinea pigs were immunized twice with OVA (day 0 and 7). On day 28, animals received a single OVA challenge. One hour before the OVA challenge, animals received either air or iJak-381 (1.3 and 6.2mpk) at the indicated dose via dry powder in halation (DPI) system. Twenty-four hours after the final challenge, lungs, spleens, and plasma were collected. |
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Dosage form |
1.3 and 6.2mpk; DPI; day 0, 7 and 28 |
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Applications |
DPI iJak-381 administration resulted in a dose dependent reduction of inflammation, with very few remaining tissue infiltrates. The lung-restricted exposure of iJak-381 in guinea pigs was observed. |
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References: |
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| Cas No. | 1831144-46-7 | SDF | |
| 别名 | iJak381; iJak 381; iJak-381; GDC-0214; GDC 0214; GDC0214; | ||
| Canonical SMILES | O=C(C1=C2N=CC=CN2N=C1)NC3=CN(CC(N4CCC(N(CCC#N)C)CC4)=O)N=C3C5=CC(Cl)=CC=C5OC(F)F | ||
| 分子式 | C28H28ClF2N9O3 | 分子量 | 612.0388 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at-20℃ |
| 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 | 1.6339 mL | 8.1694 mL | 16.3388 mL |
| 5 mM | 0.3268 mL | 1.6339 mL | 3.2678 mL |
| 10 mM | 0.1634 mL | 0.8169 mL | 1.6339 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。
Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet