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Enzymes for Research, Diagnostic and Industrial Use

SL-01

Cat No.
CEI-0887
Description
SL-01 is a p53-Mdm2 interaction inhibitor with IC50 of 3.18 μM.
CAS No.
26049-94-5
Molecular Weight
331.79
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Targets
p53, Mdm2
IC50
3.18 μM
Molecular Formula
C18H18ClNO3
Chemical Name
Carbamic acid, N-[(1S)-3-chloro-2-oxo-1-(phenylmethyl)propyl]-, phenylmethyl ester
Solubility
DMSO 50 mg/mL heat ; Water mg/mL; Ethanol 15 mg/mL heat
In vitro
SL-01 inhibits the proliferation of lung carcinoma cell lines NCI-H460 and A549, hepatocellular carcinoma cell lines Bel7402 and HepG2, and colon adenocarcinoma cell line HCT-116 with IC50s of 20, 20, 8, 6 and 20 μM, respectively, which are higher than that of gemcitabine. SL-01 induces the cancer cells to apoptosis showing chromatin condensation and externalization of phosphatidylserine. In concentrations of SL-01 from 2 to 8 μM, the percentages of apoptotic cells are increased from 16.8% to 39.6%, for NCI-H460 cells.
In vivo
SL-01 effectively inhibits human hepatocellular carcinoma HepG2 xenograft growth after 20 days of oral administration (Table 6 and Figure 2A). The rates of inhibition by 21.5, 17.2 and 12.9 μmol⁄kg of SL-01 once per day are 58.0%, 42.1% and 31.8%, respectively. In human colon adenocarcinoma HCT-116 xenografts, the rates of inhibition by SL-01 are 69.3%, 47.8% and 39.1% after 16 days of oral administration at 25.8, 21.5 and 17.2 μmol⁄kg, respectively. SL-01 is well tolerated by mice with no significant loss in body mass or other apparent signs of toxicity. The SL-01 induces NCI-H460 cells apoptosis in vivo. After 3 weeks treatment, the percentages of TUNEL staining positive cells in NCI-H460 xenografts treated by 10, 20 and 30 μmol/kg of SL-01 are 25.6%, 41.7% and 54.3%, respectively. SL-01 significantly increases the expression of cleaved caspase-9 and cleaved caspase-3. The percentages of increase in cleaved PARP by 10, 20, 30 μmol/kg of SL-01 are 42.3%, 109.3% and 133.2%, respectively. SL-01-treated cancer tissues exhibits the activation of Bax/Bcl-2 ratio.
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