DT2216 (i.p.; 7.5, 15 mg/kg; weekly for 60 days) of 15 mg/kg is more effective at suppressing the growth of MOLT-4 T-ALL xenografts in mice than 7.5 mg/kg[1]. Animal Model: CB17/Icr-Prkdcscid/IcrIcoCrl (CB-17 SCID) mice aged 5-6 weeks[1] Dosage: 7.5, 15 mg/kg Administration: i.p.; weekly for 60 days Result: Suppressed the growth of MOLT-4 T-ALL xenografts in mice.
In Vitro
DT2216 (62.5, 125 nM; 72 hours) kills MOLT-4 cells[1]. ABT263 (0.001-10 μM; 72 hour) shows highly toxic to MOLT-4 cells with an EC50 of 0.052 μM[1]. DT2216 (0.1, 0.3 μM; 24 hours) kills MOLT-4 cells by caspase-3-mediated induction of apoptosis in a BCL-2 homologous antagonist killer (BAK)- and BCL-2-associated X protein (BAX)-dependent manner[1]. Apoptosis Analysis[1] Cell Line: MOLT-4 cells Concentration: 62.5, 125 nM Incubation Time: 72 hours Result: Killed MOLT-4 cells. Cell Cytotoxicity Assay[1] Cell Line: MOLT-4 cells Concentration: 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 72 hours Result: Showed highly toxic to MOLT-4 cells with an EC50 of 0.052 μM. Western Blot Analysis[1] Cell Line: MOLT-4 cells Concentration: 0.1, 0.3 μM Incubation Time: 24 hours Result: Killed MOLT-4 cells by caspase-3-mediated induction of apoptosis in a BCL-2 homologous antagonist killer (BAK)- and BCL-2-associated X protein (BAX)-dependent manner.
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Khan S, et al. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat Med. 2019 Dec;25(12):1938-1947.
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