JAK1-IN-3
(Synonyms: Golidocitinib; AZD4205) 目录号 : GC33036
JAK1-IN-3是一种高选择性、口服活性的Janus激酶1（JAK1）抑制剂，IC50值为73nM。
Cas No.:2091134-68-6
Sample solution is provided at 25 µL, 10mM.
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JAK1-IN-3, is a highly selective, orally active Janus kinase 1 (JAK1) inhibitor with an IC50 value of 73nM[1-3]. JAK1-IN-3 has an IC50>14.7µM for JAK2[1]. JAK1-IN-3 suppresses the activation of Signal Transducer and Activator of Transcription 3 (STAT3) by inhibiting the phosphorylation of tyrosine by JAK[4]. JAK1-IN-3 can also inhibit tumor growth and demonstrates favorable drug metabolism and pharmacokinetic (DMPK) properties[2, 5].
In vitro, H1975 cells were treated with Osimertinib (250nM), JAK1-IN-3 (5µM), or both for 48 hours. The combination treatment of JAK1-IN-3 and Osimertinib significantly enhanced the inhibitory effect on cell growth compared with monotherapy[6].
In vivo, in female NCr nude mice bearing tumors, the combination treatment with JAK1-IN-3 (50mg/kg) and Osimertinib (2.5mg/kg) via oral administration showed greater tumor growth inhibition than either JAK1-IN-3 or Osimertinib alone[2].
References:
[1] Annika Birgitta Margareta ÅSTRAND, et al. Compounds and methods for inhibiting jak. WO2017050938A1.
[2] Su Q, Banks E, Bebernitz G, et al. Discovery of (2R)-N-[3-[2-[(3-Methoxy-1-methyl-pyrazol-4-yl)amino]pyrimidin-4-yl]-1H-indol-7-yl]-2-(4-methylpiperazin-1-yl)propenamide (AZD4205) as a Potent and Selective Janus Kinase 1 Inhibitor. J Med Chem. 2020;63(9):4517-4527.
[3] Song Y, Malpica L, Cai Q, et al. Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study. Lancet Oncol. 2024;25(1):117-125.
[4] Edirisinghe DT, Kaur J, Lee YQ, et al. The role of the tumour microenvironment in lung cancer and its therapeutic implications. Med Oncol. 2025;42(6):219. Published 2025 May 23.
[5] Qureshy Z, Johnson DE, Grandis JR. Targeting the JAK/STAT pathway in solid tumors. J Cancer Metastasis Treat. 2020;6:27.
[6] Kim Y, Jeon E, Ahn H, Kang J, Sim T. Identification of Thieno[3,2-d]pyrimidine derivatives as potent and selective Janus Kinase 1 inhibitors. Eur J Med Chem. 2025;286:117308.
JAK1-IN-3是一种高选择性、口服活性的Janus激酶1（JAK1）抑制剂，IC50值为73nM[1-3]。JAK1-IN-3对JAK2的IC50>14.7µM[1]。JAK1-IN-3通过抑制JAK介导的酪氨酸磷酸化，抑制信号转导及转录激活因子3（STAT3）的激活[4]。JAK1-IN-3还能够抑制肿瘤生长，并表现出良好的药物代谢和药代动力学（DMPK）特性[2, 5]。
在体外，H1975细胞分别用奥希替尼（250nM）、JAK1-IN-3（5µM）或两者联合处理48小时。与单独治疗相比，JAK1-IN-3与奥希替尼的联合治疗显著增强了对细胞生长的抑制效果[6]。
在体内，对携带肿瘤的雌性NCr裸鼠使用JAK1-IN-3（50mg/kg）和奥希替尼（2.5mg/kg）联合口服给药，联合治疗比单独使用JAK1-IN-3或奥希替尼显示出更强的肿瘤生长抑制效果[2]。
| Cell experiment [1]: | |
Cell lines | H1975 cells |
Preparation Method | Cells were incubated at 37°C in a humidified 5% CO2 incubator. All media were supplemented with 10% Fetal Bovine Serum (FBS) and 1% penicillin/streptomycin. H1975 cells were treated with Osimertinib (250nM), JAK1-IN-3 (5µM), or both for 48h. Cell viability was quantified using the assay kit. |
Reaction Conditions | 5µM; 48h |
Applications | The combination treatment of JAK1-IN-3 and Osimertinib resulted in significantly enhanced cell growth inhibition compared to single-agent treatment. |
| Animal experiment [2]: | |
Animal models | female NCr nude mice |
Preparation Method | NCI-H1975 cells were implanted subcutaneously in female NCr nude mice. Ten days after cell implantation, mice were randomized into groups of six to eight mice (average tumor volume, 189mm3; range, 152 to 250mm3) and dosed orally with either vehicle (20% Captisol), JAK1-IN-3 (Quaque Die), Osimertinib (Bis in Die), or the combination of JAK1-IN-3 plus Osimertinib at the indicated doses and schedules for 18 days. |
Dosage form | 2.5mg/kg (JAK1-IN-3), 50mg/kg (Osimertinib); orally |
Applications | In the combination-treated groups, the addition of JAK1-IN-3 enhanced the antitumor activity of Osimertinib compared to treatment with Osimertinib alone. When JAK1-IN-3 was administered as a single agent, JAK1-IN-3 had only weak antitumor activity relative to vehicle control treatment. On the last day of treatment, the inhibition of tumor growth of the combination treatments was statistically significant compared to single-agent Osimertinib. |
References: | |
| Cas No. | 2091134-68-6 | SDF | |
| 别名 | Golidocitinib; AZD4205 | ||
| Canonical SMILES | C[C@@H](N1CCN(C)CC1)C(NC2=C3C(C(C4=NC(NC5=CN(C)N=C5OC)=NC=C4)=CN3)=CC=C2)=O | ||
| 分子式 | C25H31N9O2 | 分子量 | 489.57 |
| 溶解度 | DMSO: 250 mg/mL (510.65 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 | 2.0426 mL | 10.213 mL | 20.4261 mL |
| 5 mM | 0.4085 mL | 2.0426 mL | 4.0852 mL |
| 10 mM | 0.2043 mL | 1.0213 mL | 2.0426 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
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet