GDC-0152

製品コードS7010 バッチS701003

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H34N6O3S
分子量 498.64 CAS No. 873652-48-3
Solubility (25°C)* 体外 DMSO 99 mg/mL (198.54 mM)
Ethanol 99 mg/mL (198.54 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
30%propylene glycol 5%Tween80 65%D5W
5.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of clarified propylene glycol stock solution of 16.67 mg/ml to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 GDC-0152 is a potent antagonist of XIAP-BIR3, ML-IAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 28 nM, 14 nM, 17 nM and 43 nM in cell-free assays, respectively; less affinity shown to cIAP1-BIR2 and cIAP2-BIR2. Phase 1.
in vitro GDC-0152 can block protein−protein interactions that involve IAP proteins and pro-apoptotic molecules. Using transiently transfected HEK293T cells, GDC-0152 is shown to disrupt XIAP binding to partially processed caspase-9 and to disrupt the association of ML-IAP, cIAP1, and cIAP2 with Smac. In melanoma SK-MEL28 cells, the endogenous association of ML-IAP and Smac is effectively also abolished by GDC-0152. GDC-0152 lead to a decrease in cell viability in the MDA-MB-231 breast cancer cell line, while having no effect on normal human mammary epithelial cells (HMEC). GDC-0152 is found to activate caspases 3 and 7 in a dose- and time-dependent manner. GDC-0152 is shown to induce rapid degradation of cIAP1 in A2058 melanoma cells. It effectively induces degradation of cIAP1 at concentrations as low as 10 nM, consistent with its affinity for cIAP1.
in vivo GDC-0152 has moderate predicted hepatic clearance based on metabolic stability assays conducted using human liver microsomes. Plasma−protein binding of GDC-0152 is moderate and comparable among mice (88−91%), rats (89−91%), dogs (81−90%), monkeys (76−85%), and humans (75−83%) over the range of concentrations investigated (0.1−100 μM); higher plasma−protein binding is observed in rabbits (95−96%). GDC-0152 does not preferentially distribute to red blood cells with blood−plasma partition ratios ranging from 0.6 to 1.1 in all species tested. The pharmacokinetics for GDC-0152 is achieved with a C max of 53.7 μM and AUC of 203.5 h•μM. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Fluorescence polarization-based competition assay
Inhibition constants ( Ki ) for the antagonists are determined by addition of the IAP protein constructs to wells containing serial dilutions of the antagonists or the peptide AVPW, and the Hid-FAM probe or AVP-diPhe-FAM probe, as appropriate, in the polarization buffer. Samples are read after a 30-minute incubation. Fluorescence polarization values are plotted as a function of the antagonist concentration, and the IC50 values are obtained by fitting the data to a 4-parameter equation using software. Ki values for the antagonists are determined from the IC50 valued.
細胞アッセイ 細胞株 MDA-MB-231, Normal human mammary epithelial cells (HMECs)
濃度 ~1 μM
反応時間 72 h
実験の流れ MDA-MB-231 breast carcinoma cells and HMECs are treated with the indicated concentrations of GDC-0152. Cell death is assessed using the CellTiter-Glo luminescent cell viability assay 72 h following the start of treatment.
動物実験 動物モデル human-tumor xenograft mouse models of MDA-MB-231 breast cancer
投薬量 10, 50, or 100 mg/kg
投与方法 oral gavage

カスタマーフィードバック

, , PLoS One, 2015, 10(5):e0128647.

Data from [Data independently produced by , , Cell Death Dis, 2016, 7(8):e2325]

Data from [Data independently produced by , , Endocr Relat Cancer, 2018, 25(3):295-308]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore [ Nat Commun, 2023, 14(1):1461] PubMed: 37015934
Protein folding stress potentiates NLRP1 and CARD8 inflammasome activation [ Cell Rep, 2023, 42(1):111965] PubMed: 36649711
In vitro analysis reveals necroptotic signaling does not provoke DNA damage or HPRT mutations [ Cell Death Dis, 2020, 11(8):680] PubMed: 32826875
Smac Mimetics Can Provoke Lytic Cell Death That Is Neither Apoptotic Nor Necroptotic [ Apoptosis, 2020, 21] PubMed: 32440848
EBV(LMP1)-induced metabolic reprogramming inhibits necroptosis through the hypermethylation of the RIP3 promoter. [ Theranostics, 2019, 9(9):2424-2438] PubMed: 31131045
HTiP: High-Throughput Immunomodulator Phenotypic Screening Platform to Reveal IAP Antagonists as Anti-cancer Immune Enhancers [ Cell Chem Biol, 2019, 26(3):331-339] PubMed: 30639259
WX20120108, a novel IAP antagonist, induces tumor cell autophagy via activating ROS-FOXO pathway. [ Acta Pharmacol Sin, 2019, 10.1038/s41401-019-0253-5] PubMed: 31316176
Enteroendocrine Progenitor Cell-Enriched miR-7 Regulates Intestinal Epithelial Proliferation in an Xiap-Dependent Manner. [ Cell Mol Gastroenterol Hepatol, 2019, 10.1016/j] PubMed: 31756561
Inhibitor of Apoptosis Proteins Determines Glioblastoma Stem-Like Cell Fate in an Oxygen-Dependent Manner [ Stem Cells, 2019, 37(6):731-742] PubMed: 30920104
SMAC Mimetics Induce Autophagy-Dependent Apoptosis of HIV-1-Infected Resting Memory CD4+ T Cells. [ Cell Host Microbe, 2018, 24(5):689-702] PubMed: 30344003

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。