Sabutoclax is a novel and effective pan-Bcl-2 antagonist with IC50 values of 0.31, 0.32, 0.20, and 0.62μM for inhibiting the binding of BH3 peptides to Bcl-XL, Bcl-2, Mcl-1, and Bfl-1. It potently inhibited cell growth of human prostate cancer PC-3, lung cancer H460, and lymphoma cell BP3 with EC50 values of 0.13, 0.56, and 0.049μM, respectively. Consistent with this in vitro study, Sabutoclax displayed antitumor efficacy in vivo as administration of Sabutoclax at 5mg/kg, i.p., every 2 days (total of nine injections), suppressed tumor growth of prostate cancer M2182 xenograft mouse model. Sabutoclax at 1μM significantly increased the apoptosis of BC LSCs measured by cleaved capase-3 and PI staining in vitro and sensitized marrow niche-engrafted BC LSCs to Dasatinib in vivo at 5mg/kg.
Sabutoclax 细胞实验
Cell Line
Concentration
Treated Time
Description
References
PANC-1
750 nM
48 h
Sabutoclax induces G1-S phase cell cycle arrest
Cancer Res. 2015 Jun 1;75(11):2305-15.
MIA PaCa-2
750 nM
48 h
Sabutoclax induces G1-S phase cell cycle arrest
Cancer Res. 2015 Jun 1;75(11):2305-15.
AsPC-1
750 nM
48 h
Sabutoclax induces G1-S phase cell cycle arrest
Cancer Res. 2015 Jun 1;75(11):2305-15.
T315I-BV173 cells
80 nM
7-10 days
Inhibited cell growth and colony formation
Cancer Res. 2018 Oct 15;78(20):5793-5807.
SUP-B15 cells
80 nM
7-10 days
Inhibited cell growth and colony formation
Cancer Res. 2018 Oct 15;78(20):5793-5807.
BV173 cells
80 nM
7-10 days
Inhibited cell growth and colony formation
Cancer Res. 2018 Oct 15;78(20):5793-5807.
BxPC-3
500 nM
24 h
To evaluate the effect of Sabutoclax and Minocycline combination on pancreatic cancer cells, results showed significant inhibition of cell proliferation and induction of cell death.
Cancer Res. 2015 Jun 1;75(11):2305-15.
AsPC-1
500 nM
24 h
To evaluate the effect of Sabutoclax and Minocycline combination on pancreatic cancer cells, results showed significant inhibition of cell proliferation and induction of cell death.
Cancer Res. 2015 Jun 1;75(11):2305-15.
PANC-1
500 nM
24 h
To evaluate the effect of Sabutoclax and Minocycline combination on pancreatic cancer cells, results showed significant inhibition of cell proliferation and induction of cell death.
Cancer Res. 2015 Jun 1;75(11):2305-15.
MIA PaCa-2
500 nM
24 h
To evaluate the effect of Sabutoclax and Minocycline combination on pancreatic cancer cells, results showed significant inhibition of cell proliferation and induction of cell death.
Cancer Res. 2015 Jun 1;75(11):2305-15.
DU-145 cells
520 nM
48 h
To evaluate the pro-apoptotic effect of BI-97C1 in combination with mda-7/IL-24 on DU-145 cells, the results showed that the combination treatment significantly promoted apoptosis.
Proc Natl Acad Sci U S A. 2011 May 24;108(21):8785-90.
PC3 cells
750 nM
48 h
To evaluate the cytotoxicity of BI-97C1 on PC3 cells, the results showed that BI-97C1 significantly reduced cell survival.
Proc Natl Acad Sci U S A. 2011 May 24;108(21):8785-90.
PC-3 cells
30-3000 nM
72 h
To evaluate the synergistic effect of Sabutoclax with docetaxel, results showed significant synergy between Sabutoclax and docetaxel
Neoplasia. 2012 Jul;14(7):656-65.
Sabutoclax 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
BC LSC engraftment model
Intravenous
5 mg/kg
Biweekly for 4 doses
Sabutoclax inhibits BC LSC survival in the marrow niche and sensitizes them to dasatinib
Cell Stem Cell. 2013 Mar 7;12(3):316-28
Nude mice
Subcutaneous xenograft model
Intraperitoneal injection
1 mg/kg
3 times per week, continuous treatment
To evaluate the effect of Sabutoclax and Minocycline combination on pancreatic cancer mouse models, results showed significant inhibition of tumor growth and extended survival.
Cancer Res. 2015 Jun 1;75(11):2305-15.
NOD/SCID/IL-2R γnull mice
Ph+ ALL mouse model
Intraperitoneal injection
5 mg/kg
Every other day for a total of seven doses (14 days)
Suppressed leukemia burden
Cancer Res. 2018 Oct 15;78(20):5793-5807.
Athymic nude mice
Subcutaneous xenograft model
Intraperitoneal injection
1 mg/kg
3 times per week, until the end of the experiment
Sabutoclax alone reduces tumor growth, and the effect is enhanced with the addition of Minocycline
Cancer Res. 2015 Jun 1;75(11):2305-15.
Nude mice
M2182 human prostate tumor xenograft model
Intraperitoneal injection
3 mg/kg
3 times per week for 3 weeks
To evaluate the tumor growth inhibitory effect of BI-97C1 in combination with mda-7/IL-24 on the M2182 human prostate tumor xenograft model, the results showed that the combination treatment significantly inhibited tumor growth.
Proc Natl Acad Sci U S A. 2011 May 24;108(21):8785-90.
Mice
Tgfbr2ColTKO mouse model
Intraperitoneal injection
5 mg/kg
Three times per week for two weeks
To evaluate the therapeutic effect of Sabutoclax on castrate-resistant prostate cancer, results showed Sabutoclax significantly reduced tumor volume and increased apoptosis
Cytotoxicity against human H460 cells after 3 days by ATP-LITE assay, EC50=0.78 μM
20443627
human PC3 cells
Cytotoxic assay
3 days
Cytotoxicity against human PC3 cells after 3 days by ATP-LITE assay, EC50=4.64 μM
20443627
MEF
30 μM
Function assay
24 h
Induction of apoptosis in MEF expressing wild type Bcl-2 protein at 30 uM after 24 hrs by FITC-conjugated annexin V and propidium iodide staining-based FACS analysis
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