Synonym
GNE-477; GNE477; GNE 477
IUPAC/Chemical Name
5-(7-methyl-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine
InChi Key
AKKCGLXULFRAET-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
NC1=NC=C(C2=NC(N3CCOCC3)=C4C(C(C)=C(CN5CCN(S(=O)(C)=O)CC5)S4)=N2)C=N1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
GNE-477 is a potent and efficacious dual PI3K (IC50=4 nM)/mTOR(Ki=21 nM) inhibitor.
In vitro activity:
GNE-477 exerted an obvious inhibitory effect on U87 and U251 cells, and the effect on the viability of the two cell lines was dose-dependent (Figures 1B,C).
Reference: Front Pharmacol. 2021 Jul 26;12:659511. https://pubmed.ncbi.nlm.nih.gov/34381355/
In vivo activity:
Tumor growth curve results, Figure 4A, demonstrated that intraperitoneal (i.p.) injection of GNE-477, at 10 or 50 mg/kg (daily, for 3 weeks), potently inhibited RCC1 xenograft tumor growth in nude mice.
Reference: Aging (Albany NY). 2020 May 18;12(10):9489-9499. https://pubmed.ncbi.nlm.nih.gov/32421688/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
20.8 |
41.29 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
504.63
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Wang Y, Shen H, Sun Q, Zhao L, Liu H, Ye L, Xu Y, Cai J, Li Y, Gao L, Tan Y, Liu B, Chen Q. The New PI3K/mTOR Inhibitor GNE-477 Inhibits the Malignant Behavior of Human Glioblastoma Cells. Front Pharmacol. 2021 Jul 26;12:659511. doi: 10.3389/fphar.2021.659511. PMID: 34381355; PMCID: PMC8350478.
2. Ye X, Ruan JW, Huang H, Huang WP, Zhang Y, Zhang F. PI3K-Akt-mTOR inhibition by GNE-477 inhibits renal cell carcinoma cell growth in vitro and in vivo. Aging (Albany NY). 2020 May 18;12(10):9489-9499. doi: 10.18632/aging.103221. Epub 2020 May 18. PMID: 32421688; PMCID: PMC7288912.
In vitro protocol:
1. Wang Y, Shen H, Sun Q, Zhao L, Liu H, Ye L, Xu Y, Cai J, Li Y, Gao L, Tan Y, Liu B, Chen Q. The New PI3K/mTOR Inhibitor GNE-477 Inhibits the Malignant Behavior of Human Glioblastoma Cells. Front Pharmacol. 2021 Jul 26;12:659511. doi: 10.3389/fphar.2021.659511. PMID: 34381355; PMCID: PMC8350478.
2. Ye X, Ruan JW, Huang H, Huang WP, Zhang Y, Zhang F. PI3K-Akt-mTOR inhibition by GNE-477 inhibits renal cell carcinoma cell growth in vitro and in vivo. Aging (Albany NY). 2020 May 18;12(10):9489-9499. doi: 10.18632/aging.103221. Epub 2020 May 18. PMID: 32421688; PMCID: PMC7288912.
In vivo protocol:
1. Wang Y, Shen H, Sun Q, Zhao L, Liu H, Ye L, Xu Y, Cai J, Li Y, Gao L, Tan Y, Liu B, Chen Q. The New PI3K/mTOR Inhibitor GNE-477 Inhibits the Malignant Behavior of Human Glioblastoma Cells. Front Pharmacol. 2021 Jul 26;12:659511. doi: 10.3389/fphar.2021.659511. PMID: 34381355; PMCID: PMC8350478.
2. Ye X, Ruan JW, Huang H, Huang WP, Zhang Y, Zhang F. PI3K-Akt-mTOR inhibition by GNE-477 inhibits renal cell carcinoma cell growth in vitro and in vivo. Aging (Albany NY). 2020 May 18;12(10):9489-9499. doi: 10.18632/aging.103221. Epub 2020 May 18. PMID: 32421688; PMCID: PMC7288912.
1. Heffron, T.P., Berry, M., Castanedo, G., et al. Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor Bioorg. Med. Chem. Lett. 20(8), 2408-2411 (2010).
2. Wang Y, Shen H, Sun Q, Zhao L, Liu H, Ye L, Xu Y, Cai J, Li Y, Gao L, Tan Y, Liu B, Chen Q. The New PI3K/mTOR Inhibitor GNE-477 Inhibits the Malignant Behavior of Human Glioblastoma Cells. Front Pharmacol. 2021 Jul 26;12:659511. doi: 10.3389/fphar.2021.659511. PMID: 34381355; PMCID: PMC8350478.
3. Ye X, Ruan JW, Huang H, Huang WP, Zhang Y, Zhang F. PI3K-Akt-mTOR inhibition by GNE-477 inhibits renal cell carcinoma cell growth in vitro and in vivo. Aging (Albany NY). 2020 May 18;12(10):9489-9499. doi: 10.18632/aging.103221. Epub 2020 May 18. PMID: 32421688; PMCID: PMC7288912.
