ChemicalBook CAS DataBase List 1448584-12-0

1448584-12-0

Name	S55746
CAS	1448584-12-0
Molecular Formula	C43H42N4O6
MDL Number	MFCD31715456
Molecular Weight	710.82
MOL File	1448584-12-0.mol

Chemical Properties

storage temp.	Store at -20°C
solubility	DMSO : 50 mg/mL (70.34 mM);Water : < 0.1 mg/mL (insoluble)
form	Solid
color	White to off-white

Safety Data

Symbol(GHS)	GHS07
Signal word	Warning
Hazard statements	H302-H315-H319-H335
Precautionary statements	P261-P305+P351+P338

Hazard Information

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

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