| Identification | Back Directory | [Name]
CZ415 | [CAS]
1429639-50-8 | [Synonyms]
CZ415
CS-2392
CZ 415;CZ-415
CZ415 (Free base)
(S)-1-(4-(7,7-dimethyl-4-(3-methylmorpholino)-6,6-dioxido-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea
Urea, N-[4-[5,7-dihydro-7,7-dimethyl-4-[(3S)-3-methyl-4-morpholinyl]-6,6-dioxidothieno[3,4-d]pyrimidin-2-yl]phenyl]-N'-ethyl- | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C22H29N5O4S | [MDL Number]
MFCD30533321 | [MOL File]
1429639-50-8.mol | [Molecular Weight]
459.56 |
| Chemical Properties | Back Directory | [Boiling point ]
611.4±55.0 °C(Predicted) | [density ]
1.287±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:73.67(Max Conc. mg/mL);160.3(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:6):0.1(Max Conc. mg/mL);0.22(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);65.28(Max Conc. mM)
Ethanol:10.0(Max Conc. mg/mL);21.76(Max Conc. mM) | [form ]
A crystalline solid | [pka]
13.79±0.46(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
CZ415 is an inhibitor of mammalian target of rapamycin (mTOR; Kd = 6.3 nM). It is 1,000-fold selective for mTOR over a panel of 285 kinases. CZ415 inhibits phosphorylation of S6 ribosomal protein (S6RP) and Akt in HEK293T cells (IC50s = 14.5 and 14.8 nM, respectively). It inhibits IFN-γ secretion in IL-2, anti-CD3, and anti-CD28 antibody-stimulated human whole blood (IC50 = 226 nM). CZ415 (10 mg/kg) reduces fore paw joint erythema and swelling in a mouse model of collagen-induced arthritis. It also inhibits intratumor mTOR activity and reduces tumor growth in an OCC-1 oral cavity carcinoma mouse xenograft model when administered at a dose of 20 mg/kg. | [Uses]
CZ415 is a selective and potent ATP-competitive mTOR inhibitor (1). It demonstrated in vivo efficacy in a semitherapeutic collagen induced arthritis (CIA) mouse model. | [in vivo]
CZ415 is a highly selective mTOR inhibitor showing in vivo efficacy in a collagen induced arthritis (CIA) model. For full characterization of CZ415 and to enable improved dose predictions, the pharmacokinetic (PK) profile is assessed in rat. PK and oral bioavailability are determined after of 1 mg/kg intravenous (iv) bolus and 3 mg/kg oral (po) administration. The observed plasma clearance, corresponding to 45% liver blood flow, suggests that sufficient levels of free compound are circulating in the animal over time. The oral uptake is rapid with a Tmaxmax of 0.5 h and bioavailability F = 44% indicates very good absorption from the gut[1]. | [IC 50]
mTOR: 8.07 (pIC50); mTORC1; mTORC2 | [References]
[1] ANDREW D. CANSFIELD. CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model[J]. ACS Medicinal Chemistry Letters, 2016, 7 8: 768-773. DOI: 10.1021/acsmedchemlett.6b00149
[2] JING XIE. Targeting mTOR by CZ415 Inhibits Head and Neck Squamous Cell Carcinoma Cells.[J]. Cellular Physiology and Biochemistry, 2018, 46 2: 676-686. DOI: 10.1159/000488724 |
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