GDC-0941 (Synonyms: GDC-0941) |
Catalog No.GC10816
One-Click Copy Product Info
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GDC-0941은 경구용이고 p110α, p110β, p110δ, p110γ에 대한 IC₅₀가 각각 3 nM, 33 nM, 3 nM, 75 nM인 고능력 및 선택적 클래스 I PI3K 범-억제제다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 957054-30-7
Sample solution is provided at 25 µL, 10mM.
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GDC-0941은 경구용이고 p110α, p110β, p110δ, p110γ에 대한 IC₅₀가 각각 3 nM, 33 nM, 3 nM, 75 nM인 고능력 및 선택적 클래스 I PI3K 범-억제제다. GDC-0941은 PI3K 발현을 억제해서 AKT 신호전달경로를 차단하고 일반적으로 AKT 인산화 및 AKT 하위 단백질들의 인산화 수준을 감소시킨다[2]. GDC-0941은 세포 및 동물 모델에서 종양 진행을 억제하기 위해 일반적으로 사용되고 있어 표적 종양 치료를 위한 병용 요법 개발에도 활용되고 있다[3].
체외 실험에서 GDC-0941을 96시간 처리하면 U87MG, PC3, MDA-MB-361 세포의 생존력을 현저하게 억제해서 IC₅₀가 각각 0.95 μM, 0.28 μM, 0.72 μM였다[4]. 10 μM GDC-0941로 Daoy 세포를 48시간 처리하면 증식이 현저하게 억제되고 세포사멸이 유도되고 세포 주기가 정지된다[5]. GDC-0941(1 μM)을 18시간 처리하면 갑상선암 세포에서 저산소 유도 HIF-1α 및 HIF-2α 발현과 HIF 활성을 억제하였다[6].
체내 실험에서 GDC-0941을 50 mg/kg/일 용량으로 15주간 경구 투여하면 MMTV-neu 쥐 유선 조직 내 p-Akt-S473 및 Ki-67 수준을 현저하게 감소시켜 종양 발생을 지연시키고 무종양 생존 기간을 연장하였다[7]. 100 mg/kg/일 용량으로 2주간 경구 투여할 때 종양 혈관에는 영향을 주지 않으면서 RIP1-Tag2 쥐의 종양 성장을 억제하였다[8].
References:
[1] Sarker D, Ang J E, Baird R, et al. First-in-human phase I study of pictilisib (GDC-0941), a potent pan–class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors[J]. Clinical cancer research, 2015, 21(1): 77-86.
[2] Chen H, Cheng M, Gao P, et al. GDC-0941 activates integrin linked kinase (ILK) expression to cause resistance to GDC-0941 in breast cancer by the tumor necrosis factor (TNF)-α signaling pathway[J]. Bioengineered, 2022, 13(4): 10944-10955.
[3] Usman M W, Gao J, Zheng T, et al. Macrophages confer resistance to PI3K inhibitor GDC-0941 in breast cancer through the activation of NF-κB signaling[J]. Cell death & disease, 2018, 9(8): 809.
[4] Folkes A J, Ahmadi K, Alderton W K, et al. The identification of 2-(1 H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno [3, 2-d] pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer[J]. Journal of medicinal chemistry, 2008, 51(18): 5522-5532.
[5] Ehrhardt M, Craveiro R B, Holst M I, et al. The PI3K inhibitor GDC-0941 displays promising in vitro and in vivo efficacy for targeted medulloblastoma therapy[J]. Oncotarget, 2014, 6(2): 802.
[6] Burrows N, Babur M, Resch J, et al. GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1α (HIF-1α) pathways[J]. The journal of clinical endocrinology & metabolism, 2011, 96(12): E1934-E1943.
[7] Wang J, Zhang Y, Xiao Y, et al. Boosting immune surveillance by low-dose PI3K inhibitor facilitates early intervention of breast cancer[J]. American journal of cancer research, 2021, 11(5): 2005.
[8] Soler A, Figueiredo A M, Castel P, et al. Therapeutic benefit of selective inhibition of p110α PI3-kinase in pancreatic neuroendocrine tumors[J]. Clinical Cancer Research, 2016, 22(23): 5805-5817.
| 세포 실험 [1]: | |
세포 라인 | Daoy 세포 |
제조 방법 | Daoy 세포는 L-글루타민, 1mM 피루브산나트륨(PAA), 1% 페니실린/스트렙토마이신(Invitrogen) 및 10 % 태아 소 혈청(FBS)이 포함된 Dulbecco Modified Eagle Medium (DMEM)에서 37 °C, 5 % CO₂ 조건으로 배양하였습니다. 2.5×10³ 개의 Daoy 세포를 96-웰 판에 파동한 후 0, 1, 2, 5, 10 μM 농도의 GDC-0941로 48시간 처리하였습니다. MTS 시약을 첨가하고 490 nm에서 흡광도를 측정하였습니다. |
반응 조건 | 0, 1, 2, 5 및 10μM; 48 시간 동안 |
응용 분야 | GDC-0941 처리는 용량 의존적으로 Daoy 세포의 생존력을 현저하게 억제하였습니다. |
| 동물 실험 [2]: | |
동물 모형 | 암컷 MMTV-neu 쥐 |
제조 방법 | 10주령 암컷 MMTV-neu 쥐에게 GDC-0941(50 mg/kg) 또는 대조 용매(0.5 % 히드록시프로필메틸셀룰로오스에 0.1 % Tween 80 포함)를 관위 투여로 1일 1회 종양이 만져질 때까지 투여하였습니다. 무종양 중앙 생존 시간을 T(50)으로 기록하였습니다. 처리 15주 후 각 그룹에서 4–5마리를 희생시키고 네 번째 쌍의 정상적으로 보이는 유선 지방엽(MFP)을 적출해 면역조직화학 분석을 실시하였습니다. |
제형 | 50mg/kg/일, 15 주 동안; p.o. |
응용 분야 | GDC-0941 처리는 쥐 유선 조직 내 p-Akt-S473 및 Ki-67 수준을 현저하게 감소시켰습니다. |
References: | |
| Cas No. | 957054-30-7 | SDF | |
| Synonyms | GDC-0941 | ||
| Chemical Name | 4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine | ||
| Canonical SMILES | CS(=O)(=O)N1CCN(CC1)CC2=CC3=C(S2)C(=NC(=N3)C4=C5C=NNC5=CC=C4)N6CCOCC6 | ||
| Formula | C23H27N7O3S2 | M.Wt | 513.64 |
| Solubility | ≥ 25.7mg/mL in DMSO, ≥ 3.59 mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9469 mL | 9.7344 mL | 19.4689 mL |
| 5 mM | 389.4 μL | 1.9469 mL | 3.8938 mL |
| 10 mM | 194.7 μL | 973.4 μL | 1.9469 mL |
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Quality Control & SDS
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- Purity: ≥98% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)