DCH36_06

Research use only, not for human use.

DCH36_06 as a bona fide is a potent p300/CBP inhibitor

DCH36_06 as a bona fide is a potent p300/CBP inhibitor(In Vitro):DCH36_06 mediated p300/CBP inhibition leading to hypoacetylation on H3K18 in leukemic cells. The suppression of p300/CBP activity retarded cell proliferation in several leukemic cell lines.In addition, DCH36_06 arrested cell cycle at G1 phase and induced apoptosis via activation of capase3, caspase9 and PARP that elucidated the molecular mechanism of its anti-proliferation activity. In transcriptome analysis, DCH36_06 altered downstream gene expression and apoptotic pathways-related genes verified by real-time PCR. (In Vivo):DCH36_06 blocked the leukemic xenograft growth in mice supporting its potential for in vivo use that underlies the therapeutic potential for p300/CBP inhibitors in clinical translation.

DCH36_06 (6.7-20 μM; 24-48 hours) treatment arrests cell cycle at G1 phase and induces apotosis in a dose-dependent manner in leukemic cells.DCH36_06 (5-10 μM; 24 hours) treatment significantly activates the cleavage of pro-caspase 3, pro-caspase 9 and PARP1 at dose-dependent manner.DCH36_06 shows potent antiproliferative activity against tested leukemia cell lines (CEM, MOLT3, MOLT4, Jurkat, MV4-11, THP-1, RS4; 11, KOPN8, Kasumi-1 and K562 cells) in a dose-dependent manner with IC50 values at single-digit micromolar range. Cell Cycle Analysis Cell Line:MV4-11 cells Concentration:6.7 μM, 20 μM Incubation Time:24 hours, 48 hours Result:Dose-dependently arrested cell cycle at G1 phase.Apoptosis Analysis Cell Line:MV4-11 cells Concentration:6.7 μM, 20 μM Incubation Time:24 hours, 48 hours Result:Significantly induced apoptosis.Western Blot Analysis Cell Line:MV4-11 cells Concentration:5 μM, 10 μM Incubation Time:24 hours Result:Significantly activated the cleavage of pro-caspase 3, pro-caspase 9 and PARP1 at dose-dependent manner.

DCH36_06 (25-50 mg/kg; intraperitoneal injection; every two days; for 20 days) blocks the leukemic xenograft growth in mice. Animal Model:MV4-11 xenograft nude miceDosage:25 mg/kg, 50 mg/kg Administration:Intraperitoneal injection; every two days; for 20 days Result:The tumor growth rate showed significant reduction in dose-dependent manner.

DCH36_06? | (5E)-1-(3-chloro-4-methylphenyl)-5-[(2E)-3-(furan-2-yl)prop-2-en-1-ylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione

Apoptosis

Apoptosis

LysRs

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593273-05-3

372.83

C18H13ClN2O3S

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (335.27 mM)

Cc(ccc(N(C(C(C(N1)=O)=CC=Cc2ccco2)=O)C1=S)c1)c1Cl

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(-20℃)

With Ice Pack

≥ 2 years