GSK 3008348 hydrochloride是一种针对整合素αvβ6（IC50=1.50nM）的小分子拮抗剂。GSK 3008348 hydrochloride还可抑制αvβ1（IC50=2.83nM）、αvβ3（IC50=12.53nM）、αvβ5（IC50=4.00nM）、αvβ8（IC50=2.26nM）的活性。
Cas No.:1629249-40-6
Sample solution is provided at 25 µL, 10mM.
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GSK 3008348 hydrochloride is a small molecule antagonist targeting integrin αvβ6 (IC50=1.50nM). GSK 3008348 hydrochloride also inhibits the activity of αvβ1 (IC50=2.83nM), αvβ3 (IC50=12.53nM), αvβ5 (IC50=4.00nM), and αvβ8 (IC50=2.26nM)[1-2]. GSK 3008348 hydrochloride can be used in research related to pulmonary fibrosis and various cancers[3-4].
In vitro, PK-15 cells were treated with GSK 3008348 hydrochloride (100nM) 1 hour before viral infection. GSK 3008348 hydrochloride significantly inhibited FMDV viral RNA (vRNA) replication and virus production[5]. NHBE cells were incubated with GSK 3008348 hydrochloride (0.26nM) for 2-24 hours. At 2 hours. GSK 3008348 hydrochloride induced the internalization of αvβ6 integrin from the cell surface; at 24 hours, GSK 3008348 hydrochloride significantly reduced the total intracellular level of αvβ6 integrin[6].
In vivo, a mouse model of bleomycin-induced pulmonary fibrosis was treated with GSK 3008348 hydrochloride (prophylactic study: 15mg/kg; s.c. osmotic pump; for 14 days; therapeutic study: 3mg/kg; intranasal inhalation; twice daily for 14 days). GSK 3008348 hydrochloride inhibited the activation of TGF-β and demonstrated a prolonged duration of action[7].
References:
[1] Procopiou PA, Anderson NA, Barrett J, et al. Discovery of ( S)-3-(3-(3,5-Dimethyl-1 H-pyrazol-1-yl)phenyl)-4-(( R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem. 2018 Sep 27;61(18):8417-8443.
[2] Han Z, Ma Y, Cao G, et al. Integrin αVβ1 regulates procollagen I production through a non-canonical transforming growth factor β signaling pathway in human hepatic stellate cells. Biochem J. 2021 May 14;478(9):1689-1703.
[3] Maden CH, Fairman D, Chalker M, et al. Safety, tolerability and pharmacokinetics of GSK3008348, a novel integrin αvβ6 inhibitor, in healthy participants. Eur J Clin Pharmacol. 2018 Jun;74(6):701-709.
[4] Maher TM, Simpson JK, Porter JC, et al. A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor. Respir Res. 2020 Mar 26;21(1):75.
[5] Tang J, Abdullah SW, Li P, et al. Heat Shock Protein 60 Is Involved in Viral Replication Complex Formation and Facilitates Foot and Mouth Virus Replication by Stabilizing Viral Nonstructural Proteins 3A and 2C. mBio. 2022 Oct 26;13(5):e0143422.
[6] Hryczanek HF, Barrett J, Barrett TN, et al. Core Modifications of GSK3335103 toward Orally Bioavailable αvβ6 Inhibitors with Improved Synthetic Tractability. J Med Chem. 2024 Nov 14;67(21):19689-19715.
[7] John AE, Graves RH, Pun KT, et al. Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis. Nat Commun. 2020 Sep 16;11(1):4659.
GSK 3008348 hydrochloride是一种针对整合素αvβ6（IC50=1.50nM）的小分子拮抗剂。GSK 3008348 hydrochloride还可抑制αvβ1（IC50=2.83nM）、αvβ3（IC50=12.53nM）、αvβ5（IC50=4.00nM）、αvβ8（IC50=2.26nM）的活性[1-2]。GSK 3008348 hydrochloride可用于肺纤维化和多种癌症的相关研究[3-4]。
在体外，GSK 3008348 hydrochloride（100nM）处理在病毒感染前1小时PK-15细胞。GSK 3008348 hydrochloride显著抑制FMDV的病毒RNA（vRNA）复制和病毒产生[5]。GSK 3008348 hydrochloride（0.26nM）孵育NHBE细胞2-24小时。在2小时，GSK 3008348 hydrochloride可诱导细胞表面的αvβ6整合素发生内化；24小时，GSK 3008348 hydrochloride可显著降低细胞内的总αvβ6整合素水平[6]。
在体内，GSK 3008348 hydrochloride（预防性研究：15mg/kg；s.c. osmotic pump；14天；治疗性研究：3mg/kg；吸入；一天两次；持续14天）处理博来霉素诱导肺纤维化的小鼠模型。GSK 3008348 hydrochloride抑制TGF-β的激活，并具有持久的作用时间[7]。
| Cell experiment [1]: | |
Cell lines | PK-15 cells (porcine kidney cell line) |
Preparation Method | PK-15 cells were pretreated with GSK 3008348 hydrochloride (100nM) prior to or concurrently with FMDV infection. |
Reaction Conditions | 100nM; 1 hour before infection. |
Applications | GSK 3008348 hydrochloride suppressed viral RNA (vRNA) replication and virus production when added prior to or concurrently with virus infection. GSK 3008348 hydrochloride inhibited FMDV replication by blocking the viral entry step. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6 mice with bleomycin-induced lung fibrosis |
Preparation Method | In prophylactic studies, GSK 3008348 hydrochloride was administered via subcutaneously implanted osmotic mini-pumps at 15mg/kg/day for 14 days post-bleomycin. In therapeutic studies, mice were dosed twice daily by intranasal (i.n.) inhalation of 3mg/kg from day 14 to day 28 post-bleomycin. |
Dosage form | 3 or 15mg/kg; s.c. osmotic pump; i.n. inhalation; daily or twice for 14days. |
Applications | GSK 3008348 hydrochloride was evaluated for its effect on TGF-β pathway biomarkers (e.g., Smad2 levels in lung tissue and BAL cells) in a murine model of lung fibrosis. |
References: | |
| Cas No. | 1629249-40-6 | SDF | |
| Canonical SMILES | O=C(O)C[C@@H](C1=CC(N2N=C(C)C=C2C)=CC=C1)CN3C[C@H](CCC(N4)=CC=C5C4=NCCC5)CC3.[x].Cl | ||
| 分子式 | C29H37N5O2.xHCl | 分子量 | |
| 溶解度 | DMSO : 11.66 mg/mL | 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。 | ||
| 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。
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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