2. PROTAC PI3K/Akt/mTOR Apoptosis
  3. PROTACs mTOR PI3K Apoptosis
  4. GP262

GP262 是一种靶向 PI3Kγ、PI3K 和 mTOR 的 PI3K/mTOR PROTAC 降解剂，在 MDA-MB-231 细胞中的 DC50 分别为 42.23 nM和 45.4 nM。GP262 可诱导 p110α 和 p110γ 的降解其 DC50 分别为 42.23 nM、227.4 nM 和 45.4 nM。GP262 在体外表现出显著的抗增殖活性并能诱导细胞凋亡 (apoptosis)。GP262 高效调控 PI3K/AKT/mTOR 信号通路，并通过泛素-蛋白酶体系统实现靶蛋白降解。GP262 在体内显示出抑制肿瘤生长的能力及良好的生物安全性。GP262 可用于白血病和三阴性乳腺癌 (TNBC) 的研究。
(粉色: mTOR 和 PI3K 配体 (HY-203618)；蓝色: VHL 配体 (HY-125845)；黑色: 连接子)。

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GP262

GP262 Chemical Structure

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规格 价格 是否有货 数量
5 mg ￥4560
3 - 4 周
10 mg 询价 3 - 4 周
25 mg 询价 3 - 4 周
50 mg 询价 3 - 4 周
100 mg 询价 3 - 4 周
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Customer Review

GP262 相关抗体

Top Publications Citing Use of Products

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PI3Kα PI3Kβ PI3Kγ PI3Kδ PI3KC2α PI3KC2β PI3KC2γ Vps34 PI3K PI3KC3 p120γ

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

GP262 is a PI3K/mTOR PROTAC degrader targeting PI3Kγ, PI3Kα and mTOR with DC50 values of 42.23 nM, 227.4 nM and 45.4 nM, respectively in MDA-MB-231 cells. GP262 induces degradation of p110α and p110γ with a DC50 of 227.4 and 42.23 nM. GP262 efficient modulates the PI3K/AKT/mTOR pathway, achieving degradation through the ubiquitin-proteasome system (UPS). GP262 also exhibits robust antiproliferative activity and induces apoptosis in vitro. GP262 exhibits tumor growth suppression capability and biosafety profile. GP262 can be used for leukemia and triple-negative breast cancer (TNBC) [1].
(Pink: mTOR and PI3K ligand (HY-203618); Blue: VHL ligand (HY-125845); Black: linker).

IC50 & Target[1]

p110α

227.4 nM (DC50)

p110γ

42.23 nM (ED50)

mTOR

45.4 nM (Kd)

体外研究
(In Vitro)

GP262 (0-5 μM，0-24 小时) 能有效降低 MDA-MB-231 细胞中 PI3K 和 mTOR 的水平，且该降解作用可被 26S 蛋白酶体抑制所减弱、能被高浓度竞争剂 (MG132 (HY-13259) 和 VH032 (HY-120217)) 所阻断，并依赖于对 VH L的招募[1]。
GP262 (8-1000 nM) 能显著抑制细胞增殖并诱导程序性细胞死亡 (凋亡)，在 MDA-MB-231、MCF-7 和 MDA-MB-361 细胞中均显示出剂量依赖性的生长抑制，其 IC50 值分别为 68.0 nM、161.6 nM 和 124.2 nM，最大抑制率 (Imax) 分别达到 65.4%、83.4% 和 97.7%；在 200 nM 浓度下能抑制 MDA-MB-231 细胞的克隆形成能力，在 MCF-7 细胞中对 mTOR 和 PI3Kα 有抑制能力并且 IC50 值为 167.6 和 40.0 nM[1]。
GP262 (8-5000 nM，24 小时) 在 THP-1 细胞中呈现出浓度依赖性的 PI3Kγ 蛋白水平降低，并在 OCI-AML3 (IC50 = 44.3 nM) 和 THP-1 细胞 (IC50 = 48.3 nM) 中表现出抗增殖效应[1]。
GP262 (1000 nM，12 小时) 使 MDA-MB-231 细胞的凋亡率增加至 32.1%[1]。
GP262 (0.03125-2 μM) 与 PI3Kα 和 mTOR 的解离常数 (Kd) 分别为 0.867 μM 和 0.479 μM[1]。
GP262 能诱导多聚泛素化依赖的蛋白酶体降解途径[1]。
GP262 对 PI3K 家族和 mTOR 激酶表现出优异的选择性，从而在 MDA-MB-231 细胞中引发了广泛的转录组改变，包括多个与细胞周期调控、癌症相关过程及凋亡相关的差异表达基因，这些改变共同表明其对细胞周期相关通路具有显著的富集效应和深远影响[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

GP262 相关抗体:

Western Blot Analysis[1]

Cell Line: MDA-MB-231 cells
Concentration: 8, 40, 200, 1000 and 5000 nM
Incubation Time: 0, 3, 6, 9, 12 and 24 h
Result: Induced degradation of p110α with a DC50 of 227.4 nM and a Dmax of 71.3%.
Induced degradation of p110γ with a DC50 of 42.23 nM and a Dmax of 88.6%.
Induced degradation of mTOR with a DC50 of 45.4 nM and a Dmax of 74.9%.
Significantly inhibited AKT activation (p-AKT) without affecting the total AKT protein levels.
Reduced p85, p-GSK and p-4EBP1 protein level.
Induced time-dependent proteolysis of mTOR and p110α at 1 μM, exhibiting significant degradation within 12 h and maximal efficiency by 24 h, and this effect was markedly attenuated upon 26S proteasome inhibition and was also inhibited by siRNA-mediated VHL knockdown (500 nM, 24 h).

Western Blot Analysis[1]

Cell Line: THP-1 cells
Concentration: 8, 40, 200, 1000 and 5000 nM
Incubation Time: 24 h
Result: Demonstrated concentration-dependent reduction of PI3Kγ protein levels (DC50 = 88.4 nM) with >70% maximal degradation efficiency achieved after 24-h treatment.
药代动力学
(Parmacokinetics)
Species Dose Route Indicator value
Rat[1] 15 mg/mL i.p. T1/2 8.25 h
Rat[1] 5 mg/mL i.v. ClF_obs 10.5 mL/min/kg
Rat[1] 15 mg/mL i.p. Tmax 7.00 h
Rat[1] 5 mg/mL i.v. T1/2 7.6 h
Rat[1] 15 mg/mL i.p. Cmax 816 ng/mL
Rat[1] 5 mg/mL i.v. C0 50993 ng/mL
Rat[1] 15 mg/mL i.p. AUClast 11068 ng·h/mL
Rat[1] 5 mg/mL i.v. AUClast 7848 ng·h/mL
Rat[1] 15 mg/mL i.p. AUCinf 12469 ng·h/mL
Rat[1] 5 mg/mL i.v. AUC0-inf 8073 ng·h/mL
Rat[1] 15 mg/mL i.p. MRTINF_obs 11.1 h
Rat[1] 5 mg/mL i.v. MRTINF_obs 2.68 h
Rat[1] 15 mg/mL i.p. F 51.5 %
Rat[1] 5 mg/mL i.v. Vd 6.96 L/kg
体内研究
(In Vivo)

GP262 (15 或2 5 mg/kg，腹腔注射，每日一次，连续给药 20 天) 在 MDA-MB-231 三阴性乳腺癌异种移植 NOD-SCI 小鼠模型中能有效降低肿瘤组织中的靶蛋白 (PI3K 和 mTOR) 水平显著抑制肿瘤生长，并且展现出优异的安全性和耐受性未引起显著的全身毒性或器官损伤[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: MDA MB-231 cells induced-female NOD-SCID mice (60-70 days old, 22-24 g)[1]
Dosage: 15 or 25 mg/kg
Administration: i.p., daily for 20 consecutive days
Result: Showed 57.8% tumor growth inhibition at 15 mg/kg and 79.2% tumor growth inhibition at 25 mg/kg.
Maintained body weight fluctuations within 10%.
Reduced PI3K and mTOR protein expression.
Decreased expression of the proliferation marker KI67.
Showed no significantly inflammatory infiltration, necrosis, or structural abnormalities in major organs (heart, liver, and kidney).
分子量

1073.31

Formula

C56H72N12O8S
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

GP262 相关分类

  • 摩尔计算器

  • 稀释计算器

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

GP262GP 262GP-262PROTACsmTORPI3KApoptosisMammalian target of RapamycinPhosphoinositide 3-kinasePROTACapoptosisLeukemiatriple-negative breast cancerInhibitorinhibitorinhibit

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