CAS NO: | 1429639-50-8 |
规格: | ≥98% |
包装 | 价格(元) |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 459.56 |
Formula | C22H29N5O4S |
CAS No. | 1429639-50-8 |
Storage | -20℃ for 3 years in powder form |
-80℃ for 2 years in solvent | |
Solubility (In vitro) | DMSO: 91 mg/mL (198.0 mM) |
Water: <1 mg/mL | |
Ethanol: <1 mg/mL | |
Other info | Chemical Name: (S)-1-(4-(7,7-dimethyl-4-(3-methylmorpholino)-6,6-dioxido-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea InChi Key: IZLPVLBNRGPOHA-AWEZNQCLSA-N InChi Code: InChI=1S/C22H29N5O4S/c1-5-23-21(28)24-16-8-6-15(7-9-16)19-25-18-17(13-32(29,30)22(18,3)4)20(26-19)27-10-11-31-12-14(27)2/h6-9,14H,5,10-13H2,1-4H3,(H2,23,24,28)/t14-/m0/s1 SMILES Code: O=C(NCC)NC1=CC=C(C2=NC(N3[C@@H](C)COCC3)=C4C(C(C)(C)S(C4)(=O)=O)=N2)C=C1 |
Synonyms | CZ415; CZ-415; CZ 415. |
In Vitro | In vitro activity: CZ415 shows no genotoxic potential and has very good cell permeability. Treatment of CZ415 leads to inhibition of phosphorylation for downstream targets of mTORC1 and mTORC2(IC50=14.5 nM for pS6RP and IC50=14.8 nM for pAKT). The immunosuppressive effect of CZ415 is measured by detecting secreted IFNγ after 18 h in stimulated human whole blood, and the resulting IC50 was 226 nM. CZ415 shows no genotoxic potential. It is neither mutagenic in a bacterial mutation assay (Ames test) nor does it show genotoxicity in the mouse lymphoma assay (MLA), in either the presence or absence of rat-liver S9 mix.
Kinase Assay: IC50 & Target: 14.5 nM (pS6RP), 14.8 nM (pAKT), 226 nM (IFNγ)
Cell Assay: Cells are seeded in 90 μL DMEM containing 2% FCS at 4x104 cells/well (for pS6RP S240/244 assay) or 8x104 cells/well (for pAKT S473 assay) in a 96well U-bottom plate. The plate is then incubated for 1h in a humidified incubator (37oC, 5% CO2) to allow cells to adhere. CZ415: 3 μM start, 8 points 1:3 dilution steps, n=2. Positive control: 1 μM PI-103 (n=8). Negative control: DMSO (n=8). 10 μL of 10x compound concentration in 1% DMSO/99% (DMEM 2% FCS) are added to the cells followed by 2 h incubation in a humidified incubator (37oC, 5% CO2). Cells are lysed by addition of 10 μL 5x Complete Lysis Buffer and gentle shaking at 4°C for 15 min. |
In Vivo | In vivo studies show that CZ415 has moderate clearance and good oral bioavailability. In an anti-CD3 mouse model CZ415 efficiently inhibits mTOR downstream signaling and, in a CIA mouse model, shows significant antiinflammatory effects. With its extraordinary selectivity, drug-like properties and proven efficacy in vivo, CZ415 represents an ideal molecule for the pharmacological investigation of mTOR pathophysiological role in vivo. |
Animal model | Male SD rats |
Formulation & Dosage | Formulated in 5% DMSO/95% (10% Kleptose in saline); 1 mg/kg; i.v. injection |
References | ACS Med Chem Lett. 2016 Jun 10;7(8):768-73. |