GDC-0326 |
| Catalog No.GC19161 |
GDC-0326은 Ki가 0.2nM인 강력하고 선택적인 PI3Kα 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1282514-88-8
Sample solution is provided at 25 µL, 10mM.
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GDC-0326 is a potent and selective PI3Kα inhibitor with a Ki of 0.2 nM.
GDC-0326 is highly selective over other kinases. In a panel of 235 kinases, only one is inhibited by >50% by GDC-0326 when tested at 1 uM. GDC-0326 is not an inhibitor of cytochrome P450 enzymes tested (IC50>10 uM against 3A4, 2C9 1A2, 2C19, 2D6), is highly permeable in MDCK cells and has thermodynamic solubility of 82 ug/mL at pH 7.4[1].
GDC-0326 is highly stable in human and rat liver microsomes, and there is a good correlation with in vivo rat clearance. It is found to have consistently low clearance and high oral bioavailability across species tested, enabling significant sustained free drug levels. Daily administration of GDC-0326 orally at 0.78, 1.56, 3.25, 6.25, or 12.5 mg/kg results in dose-dependent increase in TGI (73%, 79%, 83%, 101%, and 110%, respectively) and tumor regressions (6 PRs out of 10 animal at 6.25 and 12.5 mg/kg) when compared to vehicle treated mice. Daily administration of GDC-0326 orally at 0.78, 1.56, 3.25, 6.25, or 12.5 mg/kg also results in dose-dependent increase in TGI (73%, 97%, 97%, 122%, and 121%, respectively) in the KPL-4 xenograft model. Notably, maximum efficacy of GDC-0326 is observed at 6.25 mg/kg in the KPL-4 model based on TGI and tumor regressions (9 PRs and 1 CR out of 10 animal treated) when compared to vehicle treated mice. Doses of GDC-0326 up to 12.5 mg/kg are well tolerated based on less than 10% body weight loss (data not shown)[1].
References:
[1]. Heffron TP, et al. The Rational Design of Selective Benzoxazepin Inhibitors of the α-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of (S)-2-((2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)oxy)propanamide (GDC-0326). J Med Chem. 2016 Feb 11;59(3):985-1002.
Animal experiment: | Rats: Male Sprague-Dawley rats are dosed intravenously with 1 mg/kg of GDC-0326 prepared in 60% PEG400/10% Ethanol. Male Sprague-Dawley rats are dosed PO with 5 mg/kg of GDC-0326 in 0.5% methylcellulose with 0.2% Tween 80 (MCT)[1]. Mice: Female NCR nude mice are dosed intravenously with 1 mg/kg of GDC-0326 prepared in 60% PEG400/10% Ethanol and PO at 25 mg/kg in 0.5% methylcellulose with 0.2% Tween 80 (MCT)[1]. |
References: [1]. Heffron TP, et al. The Rational Design of Selective Benzoxazepin Inhibitors of the α-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of (S)-2-((2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)oxy)propanamide (GDC-0326). J Med Chem. 2016 Feb 11;59(3):985-1002. | |
| Cas No. | 1282514-88-8 | SDF | |
| Canonical SMILES | C[C@H](OC1=CC=C2C3=NC(C4=NC=NN4C(C)C)=CN3CCOC2=C1)C(N)=O | ||
| Formula | C19H22N6O3 | M.Wt | 382.42 |
| Solubility | DMSO : ≥ 83.3 mg/mL (217.82 mM) | 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. |
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| 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 | 2.6149 mL | 13.0746 mL | 26.1493 mL |
| 5 mM | 0.523 mL | 2.6149 mL | 5.2299 mL |
| 10 mM | 0.2615 mL | 1.3075 mL | 2.6149 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 38 reference(s) in Google Scholar.)
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