Synonym
GNE493; GNE-493; GNE 493
IUPAC/Chemical Name
2-(2-(2-aminopyrimidin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol
InChi Key
LEXMMFPAPDGYGZ-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H20N6O2S/c1-17(2,24)12-7-11-13(26-12)15(23-3-5-25-6-4-23)22-14(21-11)10-8-19-16(18)20-9-10/h7-9,24H,3-6H2,1-2H3,(H2,18,19,20)
SMILES Code
CC(O)(C1=CC2=NC(C3=CN=C(N)N=C3)=NC(N4CCOCC4)=C2S1)C
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, not in water
Shelf Life
>2 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-493 is a potent, selective, and orally available dual pan-PI3-kinase/mTOR inhibitor with IC50s of 3.4 nM, 12 nM, 16 nM, 16 nM and 32 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR.
In vitro activity:
In other primary prostate cancer cells (priCa-2 and priCa-3) and immortalized cell lines (LNCaP and PC-3), treatment with GNE-493 (250 nM) significantly increased the relative caspase-3 activity (Fig. 2G). In addition, the TUNEL positively stained nuclei ratio (Fig. 2H) was significantly increased, confirming apoptosis activation.
Reference: Cell Death Discov. 2022 Mar 16;8(1):120. https://pubmed.ncbi.nlm.nih.gov/35296639/
In vivo activity:
Figure 6A showed that in nude mice GNE-493 administration potently inhibited growth of the priCa-1 xenograft tumors. In addition, TBAR activity was significantly enhanced in GNE-493-treated tumor tissues (Fig. 6H), supporting oxidative injury response. Therefore GNE-493 oral administration blocked Akt-mTOR signaling, downregulated SphK1, induced ceramide accumulation, and oxidative injury in priCa-1 xenograft tissues.
Reference: Cell Death Discov. 2022 Mar 16;8(1):120. https://pubmed.ncbi.nlm.nih.gov/35296639/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
20.0 |
53.70 |
| DMF:PBS (pH 7.2) (1:1) |
0.5 |
1.34 |
| DMSO |
45.0 |
120.82 |
| Ethanol |
1.1 |
2.95 |
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
372.45
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. Jin L, Zhang W, Yao MY, Tian Y, Xue BX, Tao W. GNE-493 inhibits prostate cancer cell growth via Akt-mTOR-dependent and -independent mechanisms. Cell Death Discov. 2022 Mar 16;8(1):120. doi: 10.1038/s41420-022-00911-y. PMID: 35296639; PMCID: PMC8927604.
In vitro protocol:
1. Jin L, Zhang W, Yao MY, Tian Y, Xue BX, Tao W. GNE-493 inhibits prostate cancer cell growth via Akt-mTOR-dependent and -independent mechanisms. Cell Death Discov. 2022 Mar 16;8(1):120. doi: 10.1038/s41420-022-00911-y. PMID: 35296639; PMCID: PMC8927604.
In vivo protocol:
1. Jin L, Zhang W, Yao MY, Tian Y, Xue BX, Tao W. GNE-493 inhibits prostate cancer cell growth via Akt-mTOR-dependent and -independent mechanisms. Cell Death Discov. 2022 Mar 16;8(1):120. doi: 10.1038/s41420-022-00911-y. PMID: 35296639; PMCID: PMC8927604.
1: Sutherlin DP, Sampath D, Berry M, Castanedo G, Chang Z, Chuckowree I, Dotson J, Folkes A, Friedman L, Goldsmith R, Heffron T, Lee L, Lesnick J, Lewis C, Mathieu S, Nonomiya J, Olivero A, Pang J, Prior WW, Salphati L, Sideris S, Tian Q, Tsui V, Wan NC, Wang S, Wiesmann C, Wong S, Zhu BY. Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer. J Med Chem. 2010 Feb 11;53(3):1086-97. doi: 10.1021/jm901284w. PubMed PMID: 20050669.
