A-1155463 Dihydrochloride

Catalog No.S7800 Batch:S780002

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Technical Data

Formula

C35H34Cl2FN5O4S2
Molecular Weight 742.71 CAS No. 1235034-55-5(free base)
Solubility (25°C)* In vitro DMSO 100 mg/mL (134.64 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description A-1155463 Dihydrochloride, a highly potent and selective BCL-XL inhibitor, shows picomolar binding affinity to BCL-XL, and >1000-fold weaker binding to BCL-2 and related proteins BCL-W(Ki=19 nM) and MCL-1(Ki>440 nM).
Targets
BCL-XL [1]
(Cell-free assay)
<0.01 nM(Ki)
In vitro

A-1155463 Dihydrochloride disrupts BCL-XL-BIM but not BCL-2-BIM complexes in cells. A-1155463 kills BCL-XL-dependent Molt-4 cells (EC50=70 nM) but has no measurable cytotoxicity against BCL-2-dependent RS4;11 cells (EC50>5 mM). A-1155463 induces the hallmarks of apoptosis, as evidenced by the release of cytochrome c from mitochondria, caspase activation, and the accumulation of caspase-dependent sub-G0-G1 DNA content in BCL-XL-dependent H146 cells[2].
In vivo

Following a single 5 mg/kg IP dose of A-1155463 in nontumor bearing SCID-Beige mice, platelet counts fall dramatically as measured at 6 h postdose and then rebound to normal levels within 72 h. Daily Dosing at 5 mg/kg IP to SCID-Beige mice that had been inoculated with BCL-XL-dependent H146 tumor cells for 14 days causes a statistically significant inhibition of tumor growth (maximum tumor growth inhibition = 44%), which is alleviated upon cessation of dosing[1].

Protocol (from reference)

Cell Assay:

[3]
  • Cell lines

    Colorectal cell lines (ATCC)

  • Concentrations

    0-10 μM

  • Incubation Time

    72 h

  • Method

    Cells are treated with increasing concentration of A-1155463. Cells are assayed for viability after 72 h using the CellTiter-Glo luminescent cell viability assay according to the manufacturer’s protocol. Results are normalized to cells without treatment. EC50 is calculated using the GraphPad Prism software.
Animal Study:

[1]
  • Animal Models

    SCID-Beige Mice

  • Dosages

    5 mg/kg

  • Administration

    i.p.

Customer Product Validation

Data from [Data independently produced by , , Oncogenesis, 2018, 7(9):74]

Selleck's A-1155463 Dihydrochloride has been cited by 38 publications

Clearance of defective muscle stem cells by senolytics restores myogenesis in myotonic dystrophy type 1 [ Nat Commun, 2023, 14(1):4033] PubMed: 37468473
TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance [ Cell Death Dis, 2023, 14(2):102] PubMed: 36765039
Dual Targeting of Apoptotic and Signaling Pathways in T-Lineage Acute Lymphoblastic Leukemia [ Clin Cancer Res, 2023, 29(16):3151-3161] PubMed: 37363966
Co-targeting BCL-XL and MCL-1 with DT2216 and AZD8055 synergistically inhibit small-cell lung cancer growth without causing on-target toxicities in mice [ Cell Death Discov, 2023, 9(1):1] PubMed: 36588105
Co-targeting BCL-XL and MCL-1 with DT2216 and AZD8055 synergistically inhibit small-cell lung cancer growth without causing on-target toxicities in mice [ Cell Death Discov, 2023, 9(1):1] PubMed: 36588105
The centrosomal protein 131 participates in the regulation of mitochondrial apoptosis [ Commun Biol, 2023, 6(1):1271] PubMed: 38102401
Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma [ iScience, 2023, 26(8):107369] PubMed: 37539026
Regulation of mitochondrial proteostasis by the proton gradient [ EMBO J, 2022, 41(16):e110476] PubMed: 35912435
Cancer cell-intrinsic resistance to BiTE therapy is mediated by loss of CD58 costimulation and modulation of the extrinsic apoptotic pathway [ J Immunother Cancer, 2022, 10(3)e004348] PubMed: 35296559
BCL6 inhibition ameliorates ruxolitinib resistance in CRLF2-rearranged acute lymphoblastic leukemia [ Haematologica, 2022, 10.3324/haematol.2022.280879] PubMed: 36005560

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.