GNE-477dual PI3K/mTOR inhibitor CAS# 1032754-81-6 |
- AZD8055
Catalog No.:BCC3629
CAS No.:1009298-09-2
- PP242
Catalog No.:BCC3682
CAS No.:1092351-67-1
- Torin 1
Catalog No.:BCC3676
CAS No.:1222998-36-8
- Everolimus (RAD001)
Catalog No.:BCC3594
CAS No.:159351-69-6
- Temsirolimus
Catalog No.:BCC3678
CAS No.:162635-04-3
- Rapamycin (Sirolimus)
Catalog No.:BCC3592
CAS No.:53123-88-9
Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
| Cas No. | 1032754-81-6 | SDF | Download SDF |
| PubChem ID | 25207689 | Appearance | Powder |
| Formula | C21H28N8O3S2 | M.Wt | 504.63 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 16.67 mg/mL (33.03 mM; Need ultrasonic) | ||
| Chemical Name | 5-[7-methyl-6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine | ||
| SMILES | CC1=C(SC2=C1N=C(N=C2N3CCOCC3)C4=CN=C(N=C4)N)CN5CCN(CC5)S(=O)(=O)C | ||
| Standard InChIKey | AKKCGLXULFRAET-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C21H28N8O3S2/c1-14-16(13-27-3-5-29(6-4-27)34(2,30)31)33-18-17(14)25-19(15-11-23-21(22)24-12-15)26-20(18)28-7-9-32-10-8-28/h11-12H,3-10,13H2,1-2H3,(H2,22,23,24) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | GNE-477 is a potent and efficacious dual PI3K (IC50=4 nM)/mTOR(Ki=21 nM) inhibitor.In Vitro:GNE-477 (Compound 8) has improved potency in the MCF7.1 cell proliferation assay with an EC50 of 143 nM[1].In Vivo:GNE-477 also exhibits stasis in a PC3 tumor growth inhibition study. In an experiment evaluating the tumor growth inhibition of a PC3 tumor xenograft over 14 days, stasis is achieved at a 20 mg/kg QD dose and significant inhibition is observed with doses as low as 1 mg/kg QD. GNE-477 is generally well tolerated during this study as demonstrated by acceptable levels of weight loss comparable to that observed with the animals in the vehicle cohort[1]. References: | |||||
GNE-477 Dilution Calculator
GNE-477 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9816 mL | 9.9082 mL | 19.8165 mL | 39.633 mL | 49.5412 mL |
| 5 mM | 0.3963 mL | 1.9816 mL | 3.9633 mL | 7.9266 mL | 9.9082 mL |
| 10 mM | 0.1982 mL | 0.9908 mL | 1.9816 mL | 3.9633 mL | 4.9541 mL |
| 50 mM | 0.0396 mL | 0.1982 mL | 0.3963 mL | 0.7927 mL | 0.9908 mL |
| 100 mM | 0.0198 mL | 0.0991 mL | 0.1982 mL | 0.3963 mL | 0.4954 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
IC50: 4 and 21 nmol/L for PI3K and mTOR, respectively
GNE-477 is a potent dual PI3K/mTOR inhibitor. Owing to the common association with oncogenic malignancies, the PI3K/AKT/mTOR signaling pathway is regarded as an attractive area of research for the identification of oral small molecule inhibitors.
In vitro: GNE-477 was found to inhibit PI3K-α, β, δ, and γ with IC50s of 4, 86, 6, and 15 nM, respectively. [1].
In vivo: A direct comparison of GNE-477 with its des-methyl analog revealed that the trend of reduced in vivo clearance in rats is also observed in dogs and mice. The clearance improvement was significant in dogs where the des-methyl analog was cleared at two-thirds the rate of hepatic blood flow while GNE-477 had low clearance. In an study evaluating the tumor growth inhibition of a PC3 tumor xenograft10 over 14 days, stasis was achieved at a 20 mg/kg QD dose of GNE-477 and significant inhibition was found with doses as low as 1 mg/kg QD. GNE-477 was generally well tolerated during this study as shown by acceptable levels of weight loss comparable to that in the vehicle cohort [1].
Clinical trial: N/A
Reference:
[1] Heffron TP,Berry M,Castanedo G,Chang C,Chuckowree I,Dotson J,Folkes A,Gunzner J,Lesnick JD,Lewis C,Mathieu S,Nonomiya J,Olivero A,Pang J,Peterson D,Salphati L,Sampath D,Sideris S,Sutherlin DP,Tsui V,Wan NC,Wang S,Wong S,Zhu BY. Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor. Bioorg Med Chem Lett.2010 Apr 15;20(8):2408-11.
- BAY 80-6946 (Copanlisib)
Catalog No.:BCC4986
CAS No.:1032568-63-0
- L-655,240
Catalog No.:BCC7156
CAS No.:103253-15-2
- MK-2206 dihydrochloride
Catalog No.:BCC1274
CAS No.:1032350-13-2
- D-Arabinose
Catalog No.:BCN3791
CAS No.:10323-20-3
- A939572
Catalog No.:BCC5305
CAS No.:1032229-33-6
- Fmoc-Cys(Trt)-OH
Catalog No.:BCC3479
CAS No.:103213-32-7
- Fmoc-Tyr(3,5-I2)-OH
Catalog No.:BCC3264
CAS No.:103213-31-6
- Pranlukast
Catalog No.:BCC4827
CAS No.:103177-37-3
- 14-Norpseurotin A
Catalog No.:BCN7262
CAS No.:1031727-34-0
- UNC 3230
Catalog No.:BCC5618
CAS No.:1031602-63-7
- 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile hydrobromide
Catalog No.:BCC8648
CAS No.:103146-26-5
- ABT-046
Catalog No.:BCC1326
CAS No.:1031336-60-3
- GDC-0980 (RG7422)
Catalog No.:BCC4992
CAS No.:1032754-93-0
- PTIQ
Catalog No.:BCC7953
CAS No.:1032822-42-6
- GSK1292263
Catalog No.:BCC3786
CAS No.:1032823-75-8
- LDK378
Catalog No.:BCC3691
CAS No.:1032900-25-6
- Taltirelin
Catalog No.:BCC5271
CAS No.:103300-74-9
- Pre-schisanartanin B
Catalog No.:BCN5846
CAS No.:1033288-92-4
- 3-Oxo-4-aza-5-alpha-androstane-17β-carboxylic acid
Catalog No.:BCC8641
CAS No.:103335-55-3
- L-364,373
Catalog No.:BCC7445
CAS No.:103342-82-1
- 1-Methyl-L-4,5-dihydroorotic acid
Catalog No.:BCC8472
CAS No.:103365-69-1
- GNE-493
Catalog No.:BCC8048
CAS No.:1033735-94-2
- Itol A
Catalog No.:BCN5847
CAS No.:1033747-78-2
- GNF-5837
Catalog No.:BCC3668
CAS No.:1033769-28-6
Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor.[Pubmed:20346656]
Bioorg Med Chem Lett. 2010 Apr 15;20(8):2408-11.
Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modification resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor.
