Description
S55746 (Bcl201, Servier-1) is orally available and has been reported to effectively kill cancer cells that overexpress Bcl-2 using both in vitro and in vivo models. Currently, S55746 as a single agent is in phase-I trials in relapsed or refractory CLL patients. As a sensitizing agent, S55746 is currently being tested for a combination use with PI3Kδinhibitor for follicular lymphoma and mantle cell lymphoma.
Uses
S55746 (BCL201) is a potent, orally active and selective BCL-2 inhibitor, with a Ki of 1.3 nM and a Kd of 3.9 nM. S55746 (BCL201) has antitumor activity with low toxicity[1].
in vivo
S55746 is a highly efficacious and well-tolerated (even at doses up to 300 mg/kg) orally active BCL-2 inhibitor[1].
S55746 (20-100 mg/kg, p.o.) inhibits xenograft growth in RS4;11 and Toledo models time- and dose-dependently[1].
| Animal Model: | Female SCID/beige mice implanted subcutaneously with 3×106 Toledo or RS4;11[1]. |
| Dosage: | 20, 50, 100 mg/kg. |
| Administration: | Oral gavage daily for 7 consecutive days. |
| Result: | Induced significant anti-tumor activity time- and dose-dependently. |
| Animal Model: | SCID/beige female mice with RS4;11 tumor xenografts[1]. |
| Dosage: | 25 and 100 mg/kg. |
| Administration: | Single oral gavage treatment. |
| Result: | Did not induce platelet loss in vivo at 25 and 100 mg/kg. |
IC 50
Bcl-2: 1.3 nM (Ki); Bcl-xL: 520 nM (Ki); Bcl-2: 3.9 nM (Kd); Bcl-xL: 186 nM (Kd)
References
[1] Casara P, et al. S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth. Oncotarget. 2018 Apr 13;9(28):20075-20088. DOI:
10.18632/oncotarget.24744
