GSK2636771

Name: GSK2636771
SKU: GC17109
Availability: InStock
Rating: 5 (30 reviews)

目录号 : GC17109

GSK2636771 是一种有效的三磷酸腺苷竞争性口服 PI3Kβ 抑制剂，对催化亚基 p110β 的 IC50 为 5.2 nmol/L，同时比 p110α 和 p110γ 显示出 >900 倍的选择性和 >10 倍的选择性p110δ.用 p110β 抑制剂 GSK2636771 和 AZD6482 处理 72 小时后，对照细胞的细胞活力明显低于 PTEN 突变体和 PTEN野生型 EEC 细胞。

GSK2636771 Chemical Structure

Cas No.:1372540-25-4

规格价格库存购买数量

10mM (in 1mL DMSO)	¥672.00	现货
5mg	¥525.00	现货
10mg	¥1,008.00	现货
50mg	¥2,510.00	现货
100mg	¥3,875.00	现货

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Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

GlpBio产品文献引用

Nature
610.7931 (2022): 366-372

Nature
618, 1017–1023 (2023)

Cell
183.7 (2020): 1867-1883

Cell Research
31, 1291–1307 (2021)

Cell Research
33, 273–287 (2023)

Cell Research
33, 546–561 (2023)

Molecular Cancer
21.1 (2022): 1-17

Molecular Cancer
21.1 (2022): 1-18

Cancer Cell
39 (2021): 1-16

Cell Host Microbe
30.8 (2022): 1124-1138

Cell Host Microbe
31.5 (2023): 766-780

Cell Host Microbe
31.3 (2023): 418-43

Cell Metabolism
34.2 (2022): 240-255

Ann Rheum Dis
82(4): 533-545 (2023)

Cell Mol Immunol
20, 264–276 (2023)

Adv Funct Mater
33.35 (2023): 2214998

产品描述实验参考方法化学性质产品文档

产品文档

Quality Control & SDS

View current batch:

Purity: >99.50%

实验参考方法

Kinase experiment [1]:
Preparation Method	Biochemical selectivity of GSK2636771 was tested using the PI3-Kinase HTRF Assay, as well as the entire panel of GSK in-house kinase selectivity assays. Affinity-enrichment-based chemoproteomics using kinobeads was performed. Briefly, 14 lipid and atypical kinases were enriched from a standard mixture of extracts derived from HeLa, K562, and Jurkat cells using a compound-derivatized bead matrix. The enriched proteins were identified by quantitative mass spectrometry analysis, enabling the simultaneous assessment of binding specificity, and potency for all detected affinity-captured proteins.
Applications	GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ with an apparent Ki value of 0.89 nmol/L (IC50 = 5.2 nmol/L), >900-fold selectivity over p110α and p110γ, and >10-fold selectivity over p110δ isoforms, while sparing other PI3K superfamily kinases.
Cell experiment [2]:
Cell lines	PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines
Preparation Method	Cell viability was determined after 72 hours of treatment with indicated concentrations of the p110β selective inhibitors GSK2636771 and AZD6482 in 3 p110β-reliant breast and prostate cancer cell lines, 7 PTEN wild-type EEC cells, and 17 PTEN-mutant EEC cells.
Reaction Conditions	1-10uM GSK2636771 for 72 hours
Applications	Upon 72 hours treatment with the p110β inhibitors GSK2636771 and AZD6482, cell viability was significantly more decreased in the control cells [ p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines] than in PTEN-mutant and PTEN wild-type EEC cells.
Animal experiment [3]:
Animal models	Female athymic nude mice (4-5-week-old)
Preparation Method	Female athymic nude mice were injected subcutaneously with ZR75-1/FR cells resuspended in matrigel. On the same date, mice were implanted subcutaneously with a 17β-estradiol pellet, and fulvestrant treatment was initiated. Four weeks after implantation, tumor-bearing mice were randomized to treatment with vehicle, GSK2636771 (30 mg/kg/d, orally), BYL719, or the combination, all with a fulvestrant treatment backbone.
Dosage form	GSK2636771 (30 mg/kg/d, orally)
Applications	Inhibition of ER/p110β or ER/p110α/βby GSK2636771 induced rapid tumor regression, whereas ER/p110α inhibition had no significant early effect on growth compared to continued ER inhibition alone.
References: [1]. Mateo J, Ganji G, et,al . A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017 Oct 1;23(19):5981-5992. doi: 10.1158/1078-0432.CCR-17-0725. Epub 2017 Jun 23. PMID: 28645941. [2]. Weigelt B, Warne PH, et,al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013 Jul 1;19(13):3533-44. doi: 10.1158/1078-0432.CCR-12-3815. Epub 2013 May 14. PMID: 23674493; PMCID: PMC3700760. [3]. Hosford SR, Dillon LM, et,al . Combined Inhibition of Both p110α and p110β Isoforms of Phosphatidylinositol 3-Kinase Is Required for Sustained Therapeutic Effect in PTEN-Deficient, ER+ Breast Cancer. Clin Cancer Res. 2017 Jun 1;23(11):2795-2805. doi: 10.1158/1078-0432.CCR-15-2764. Epub 2016 Nov 30. PMID: 27903677; PMCID: PMC5449270.

GSK2636771 is a potent adenosine triphosphate competitive oral inhibitor of PI3Kβ, with an IC50 of 5.2 nmol/L against the catalytic subunit, p110β, whilst showing >900-fold selectivity over p110α and p110γ, and >10-fold selectivity over p110δ^[3,4].

Upon 72 hours treatment with the p110β inhibitors GSK2636771 and AZD6482, cell viability was significantly more decreased in the control cells [ p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines] than in PTEN-mutant and PTEN wild-type EEC cells^[1]. GSK2636771 showed a certain inhibitory effect on several CRPC cell lines including C4-2B cell sublines, and BL140 showed a stronger inhibitory effect than GSK2636771^[6].

Inhibition of ER/p110β or ER/p110α/βby GSK2636771 induced rapid tumor regression, whereas ER/p110α inhibition had no significant early effect on growth compared to continued ER inhibition alone^[2]. To explore the therapeutic potential of simultaneously targeting Cx43 and PIK3CB/p110β, αCT1 is combined with TGX-221 or GSK2636771, two PIK3CB/p110β-selective inhibitors. These two different treatments synergistically inactivate PI3K and sensitize glioblastoma cells to temozolomide in vitro and in vivo^[5]. Combining anti-OX40 with GSK2636771, a PI3Kβ-selective inhibitor, delayed tumor growth and extended the survival of mice with PTEN-null melanomas^[7].

References:
[1]. Weigelt B, Warne PH, et,al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013 Jul 1;19(13):3533-44. doi: 10.1158/1078-0432.CCR-12-3815. Epub 2013 May 14. PMID: 23674493; PMCID: PMC3700760.
[2]. Hosford SR, Dillon LM, et,al. Combined Inhibition of Both p110α and p110β Isoforms of Phosphatidylinositol 3-Kinase Is Required for Sustained Therapeutic Effect in PTEN-Deficient, ER+ Breast Cancer. Clin Cancer Res. 2017 Jun 1;23(11):2795-2805. doi: 10.1158/1078-0432.CCR-15-2764. Epub 2016 Nov 30. PMID: 27903677; PMCID: PMC5449270.
[3]. Janku F, Yap TA, et,al. Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol. 2018 May;15(5):273-291. doi: 10.1038/nrclinonc.2018.28. Epub 2018 Mar 6. PMID: 29508857.
[4]. Mateo J, Ganji G, et,al. A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017 Oct 1;23(19):5981-5992. doi: 10.1158/1078-0432.CCR-17-0725. Epub 2017 Jun 23. PMID: 28645941.
[5]. Pridham KJ, Shah F, et,al. Connexin 43 confers chemoresistance through activating PI3K. Oncogenesis. 2022 Jan 12;11(1):2. doi: 10.1038/s41389-022-00378-7. PMID: 35022385; PMCID: PMC8755794.
[6]. He C, Duan S, et,al. Characterization of a novel p110β-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells. Prostate. 2017 Aug;77(11):1187-1198. doi: 10.1002/pros.23377. Epub 2017 Jun 20. PMID: 28631436; PMCID: PMC5527967.
[7]. Peng W, Williams LJ,et,al. Anti-OX40 Antibody Directly Enhances The Function of Tumor-Reactive CD8+ T Cells and Synergizes with PI3Kβ Inhibition in PTEN Loss Melanoma. Clin Cancer Res. 2019 Nov 1;25(21):6406-6416. doi: 10.1158/1078-0432.CCR-19-1259. Epub 2019 Aug 1. PMID: 31371342; PMCID: PMC7232853.

GSK2636771 是一种有效的三磷酸腺苷竞争性口服 PI3Kβ 抑制剂，对催化亚基 p110β 的 IC50 为 5.2 nmol/L，同时比 p110α 和 p110γ 显示出 >900 倍的选择性和 >10 倍的选择性p110δ^[3,4].

用 p110β 抑制剂 GSK2636771 和 AZD6482 处理 72 小时后，对照细胞 [p110β 依赖性 PTEN 缺陷型 PC3 前列腺癌细胞系以及 BT549 和 HCC70 乳腺癌细胞系] 的细胞活力明显低于 PTEN 突变体和 PTEN野生型 EEC 细胞^[1]。 GSK2636771对包括C4-2B细胞亚系在内的几种CRPC细胞系均表现出一定的抑制作用，其中BL140表现出比GSK2636771更强的抑制作用^[6]。

GSK2636771 抑制 ER/p110β 或 ER/p110α/β 可诱导肿瘤快速消退，而与单独持续抑制 ER 相比，ER/p110α 抑制对生长没有显着的早期影响^[2]。为了探索同时靶向 Cx43 和 PIK3CB/p110β 的治疗潜力，αCT1 与两种 PIK3CB/p110β 选择性抑制剂 TGX-221 或 GSK2636771 联合使用。这两种不同的治疗在体外和体内协同使 PI3K 失活并使胶质母细胞瘤细胞对替莫唑胺敏感^[5]。将抗 OX40 与 PI3Kβ 选择性抑制剂 GSK2636771 联合使用可延缓肿瘤生长并延长 PTEN 缺失黑色素瘤小鼠的生存期^[7]。

Cas No.	1372540-25-4	SDF
化学名	2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid
Canonical SMILES	CC1=C(C=CC=C1C(F)(F)F)CN2C(=NC3=C2C=C(C=C3C(=O)O)N4CCOCC4)C
分子式	C₂₂H₂₂F₃N₃O₃	分子量	433.42
溶解度	≥ 10.825mg/mL in DMSO	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。

溶解性数据

制备储备液
		1 mg	5 mg	10 mg
	1 mM	2.3072 mL	11.5362 mL	23.0723 mL
	5 mM	0.4614 mL	2.3072 mL	4.6145 mL
	10 mM	0.2307 mL	1.1536 mL	2.3072 mL

摩尔浓度计算器
稀释计算器
分子量计算器

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动物体内配方计算器 (澄清溶液)

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

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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

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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，注：如该浓度超过该批次药物DMSO溶解度，请先联系GLPBIO）；

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。

注意：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。

GSK2636771

Customer Reviews

B1

GlpBio产品文献引用

产品文档

Quality Control & SDS

实验参考方法

溶解性数据

摩尔浓度计算器

稀释计算器

分子量计算器

动物体内配方计算器 (澄清溶液)

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