S55746 (S 055746,BCL201)

Catalog No.S8759

S55746 (S 055746,BCL201) Chemical Structure

Molecular Weight(MW): 710.82

S55746 (S 055746,BCL201) is a novel, orally active BCL-2 specific inhibitor (Ki = 1.3 nM) with poor affinity for BCL-XL and no significant binding to MCL-1, BFL-1 (BCL2A1/A1). The selectivity of S55746 for BCL-2 versus BCL-XL ranges from ~70 to 400 folds.

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Biological Activity

Description S55746 (S 055746,BCL201) is a novel, orally active BCL-2 specific inhibitor (Ki = 1.3 nM) with poor affinity for BCL-XL and no significant binding to MCL-1, BFL-1 (BCL2A1/A1). The selectivity of S55746 for BCL-2 versus BCL-XL ranges from ~70 to 400 folds.
Targets
Bcl-2 [1]
(Cell-free assay)
1.3 nM(Ki)
In vitro

S55746 occupies the hydrophobic groove of BCL-2. In a panel of hematological cell lines, S55746 induces hallmarks of apoptosis including externalization of phosphatidylserine, caspase-3 activation and PARP cleavage. S55746 potently induces RS4;11 cell killing after 72 h of treatment with an IC50 of 71.6 nM and exhibits a much weaker activity in H146 (IC50 = 1.7 μM), a BCL-XL-dependent cell line, which expresses a low level of BCL-2 and high level of BCL-XL. It has no cytotoxic activity on BCL-XL-dependent cells, such as platelets[1].

In vivo

S55746 administered by oral route daily in mice demonstrates robust anti-tumor efficacy in two hematological xenograft models (RS4;11 and Toledo models) with no weight lost and no change in behavior[1].

Protocol

Cell Research:

[1]

+ Expand
  • Cell lines: RS4;11 cells
  • Concentrations: 0.01, 0.03, 0.1, 0.3, 1 μM
  • Incubation Time: 2 hours
  • Method:

    Apoptosis induction in RS4;11 cells treated with S55746 at various concentrations for 2 h. Cells were analyzed by flow cytometry for PI and annexin V-FITC labeling.


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: RS4;11 tumor xenografts (Female SCID mice inoculated with RS4;11 cells)
  • Formulation: PEG300/EtOH/water (40/10/50)
  • Dosages: 25 and 100 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (140.68 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 710.82
Formula

C43H42N4O6

CAS No. 1448584-12-0
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02603445 Completed Follicular Lymphoma Mantle Cell Lymphoma Novartis Pharmaceuticals|Novartis November 16 2015 Phase 1
NCT02603445 Completed Follicular Lymphoma Mantle Cell Lymphoma Novartis Pharmaceuticals|Novartis November 16 2015 Phase 1
NCT02920541 Completed Acute Myeloid Leukaemia (AML)|Myelodysplastic Syndrome (MDS) Institut de Recherches Internationales Servier|Servier January 2015 Phase 1
NCT02920541 Completed Acute Myeloid Leukaemia (AML)|Myelodysplastic Syndrome (MDS) Institut de Recherches Internationales Servier|Servier January 2015 Phase 1
NCT02920697 Completed Chronic Lymphocytic Leukaemia (CLL)|B-Cell Non-Hodgkin Lymphoma (NHL)|Multiple Myeloma (MM) Institut de Recherches Internationales Servier|Servier March 2014 Phase 1
NCT02920697 Completed Chronic Lymphocytic Leukaemia (CLL)|B-Cell Non-Hodgkin Lymphoma (NHL)|Multiple Myeloma (MM) Institut de Recherches Internationales Servier|Servier March 2014 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Bcl-2 Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID