GDC-0077 (RG6114)是一种高效且选择性的PI3Kα抑制剂，IC50值为0.038nM。
Cas No.:2060571-02-8
Sample solution is provided at 25 µL, 10mM.
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GDC-0077 (RG6114) is a potent and selective PI3Kα inhibitor with an IC50 of 0.038nM. GDC-0077 is > 300-fold more selective for PI3Kα over the other class I PI3K isoforms (β, δ, and γ) and > 2000-fold more selective over PIK family members. GDC-0077 binds to the ATP binding site of PI3K and inhibits the phosphorylation of PIP2 to PIP3[1]. GDC-0077 achieves precise targeting of PIK3CA-mutated tumors through a dual-action mechanism: selectively inhibiting PI3Kα activity and inducing the degradation of mutant p110α protein[2]. GDC-0077 is commonly used in the study of breast cancer.
GDC-0077 (0.3μM, 2 to 3 weeks) significantly inhibited proliferation in PIK3CA-mutant cell lines compared to the control. GDC-0077 combined with cobimetinib showed an increased cytotoxic response in four of five colorectal cancer cell lines[3].
GDC-0077 (25mg/kg/day, 25 days, i.g.) markedly enhanced the antitumor efficacy of the palbociclib-fulvestrant combination, elevating the mean tumor growth inhibition (TGI) from 71% to 106%[4].
References:
[1] Hong R, Edgar K, Song K, et al. Abstract PD4-14: GDC-0077 is a selective PI3Kalpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies[J]. Cancer research, 2018, 78(4_Supplement): PD4-14-PD4-14.
[2] Zhu R, Zhang H, Zhang F. Mechanistic optimization of inavolisib combined with CDK4/6 inhibitors in the treatment of PIK3CA-mutated breast tumors[J]. Frontiers in Immunology, 2025, 16: 1693927.
[3] Song K W, Ong C C, Lin E, et al. KRAS codon-specific mutations differentially toggle PI3K pathway signaling and alter sensitivity to inavolisib (GDC-0077)[J]. Molecular Cancer Therapeutics, 2025, 24(12): 1890-1901.
[4] Song K W, Edgar K A, Hanan E J, et al. RTK-dependent inducible degradation of mutant PI3Kα drives GDC-0077 (Inavolisib) efficacy[J]. Cancer discovery, 2022, 12(1): 204-219.
GDC-0077 (RG6114)是一种高效且选择性的PI3Kα抑制剂，IC50值为0.038nM。GDC-0077对PI3Kα的选择性比其他I类PI3K亚型（β、δ和γ）高300倍以上，对PIK家族成员的选择性高2000倍以上。GDC-0077与PI3K的ATP结合位点结合，抑制PIP2磷酸化为PIP3[1]。GDC-0077通过双重作用机制实现对PIK3CA突变肿瘤的精准靶向：选择性抑制PI3Kα活性并诱导突变型p110α蛋白的降解[2]。GDC-0077常用于乳腺癌的研究。
与对照组相比，GDC-0077（0.3μM，2～3周）显著抑制了PIK3CA突变细胞系的增殖。GDC-0077与cobimetinib联合用药在五种结直肠癌细胞系中的四种中显示出增强的细胞毒性反应[3]。
GDC-0077（25mg/kg/天，25天，灌胃）显著增强了palbociclib-fulvestrant联合用药的抗肿瘤疗效，使平均肿瘤生长抑制率（TGI）从71%提高到106%[4]。
| Cell experiment [1]: | |
Cell lines | PIK3CA-mutant cell lines |
Preparation Method | Twelve-well plates were seeded with 10,000 to 20,000 cells/well in a volume of 1mL and incubated at 37°C under 5% CO2 for 24 hours. Compounds (DMSO, 0.3μM GDC-0077, 0.3μM cobimetinib, or a combination of the two drugs) were added the next day at indicated concentration for 2 to 3 weeks. The medium was replaced weekly with fresh medium containing the drugs. Then the medium was aspirated and 100μL of 0.5% crystal violet was added for 15 minutes. The dye was discarded and the cells were washed with PBS for 5 to 10 minutes five times. PBS was then aspirated and the cells were imaged using GelCount. |
Reaction Conditions | 0.3μM, 2 to 3 weeks |
Applications | GDC-0077 significantly inhibited proliferation in PIK3CA-mutant cell lines compared to the control. |
| Animal experiment [2]: | |
Animal models | PIK3CA-mutated breast cancer mouse model |
Preparation Method | HCC1954 tumor cells (5×106) were inoculated in the 2/3 mammary fat pads of female NCR nude mice, whereas WHIM20 and HCI-003 tumors (50mm3) were engrafted in 2/3 mammary fat pads in female NOD-SCID gamma mice. Tumor Volume (mm3) = (Length × Width2) × 0.5. Mice for efficacy studies were distributed into 8 to 10 mice/group with a mean tumor volume of 200 to 250mm3 at the initiation of dosing. Tumor growth inhibition as a percentage of vehicle control (%TGI) was calculated as the percentage of the AUC (Area Under the Curve) for the respective dose group per day in relation to the vehicle, using the following formula: %TGI = 100 × (1 – AUCdose/AUCvehicle). The PI3K inhibitors taselisib, GDC-0941, GDC-0077, and BYL719 were formulated in methylcellulose Tween vehicle consisting of 0.5% (w/v) methylcellulose, 0.2% (w/v) polysorbate 80 (Tween-80) and dosed orally by gavage daily. Tumor sizes and mouse body weights were recorded twice weekly, and mice with tumor volume exceeding 2,000mm3 or body weight loss of 20% of starting weight were promptly euthanized. |
Dosage form | 25mg/kg/day, 25 days, i.g. |
Applications | GDC-0077 markedly enhanced the antitumor efficacy of the palbociclib-fulvestrant combination, elevating the mean tumor growth inhibition (TGI) from 71% to 106%. |
References: | |
| Cas No. | 2060571-02-8 | SDF | |
| 别名 | GDC-0077; RG6114 | ||
| Canonical SMILES | C[C@@H](C(N)=O)NC1=CC=C(C2=NC(N3[C@H](C(F)F)COC3=O)=CN2CCO4)C4=C1 | ||
| 分子式 | C18H19F2N5O4 | 分子量 | 407.37 |
| 溶解度 | DMSO : ≥ 180 mg/mL (441.86 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 | 2.4548 mL | 12.2739 mL | 24.5477 mL |
| 5 mM | 491 μL | 2.4548 mL | 4.9095 mL |
| 10 mM | 245.5 μL | 1.2274 mL | 2.4548 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。
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