| CAS NO: | 1235034-55-5 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 669.79 |
|---|---|
| Formula | C35H32FN5O4S2 |
| CAS No. | 1235034-55-5 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 100 mg/mL (149.3 mM) |
| Water: <1 mg/mL | |
| Ethanol: 100 mg/mL (149.3 mM) | |
| Solubility (In vivo) | O=C(C1=C(CCCOC2=CC=C(C#CCN(C)C)C=C2F)SC(N3CC4=C(C=CC=C4C (NC5=NC6=CC=CC=C6S5)=O)CC3)=N1)O |
| Synonyms | A-1155463; A 1155463; A1155463. |
| In Vitro | In vitro activity: A-1155463 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. Kinase Assay: A-1155463 is a highly potent and selective BCL-XL inhibitor, A-1155463 shows picomolar binding affinity to BCL-XL (Ki ＜0.01 nM), and>1000-fold weaker binding to BCL-2 (Ki = 80 nM) and related proteins BCL-W (Ki = 19 nM) and MCL-1 (Ki> 440 nM). Cell Assay: 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. |
|---|---|
| In Vivo | A-1155463 causes a mechanism-based and reversible thrombocytopenia in mice and inhibits H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses. he ability of A-1155463 to exert in vivo on-target activity was demonstrated through a rapid and reversible reduction in platelets in SCID-Beige mice following a single IP dose. Additionally, administration of A-1155463 to tumor bearing SCID-Beige mice afforded modest but statistically significant tumor growth inhibition. Detailed mechanistic studies of A-1155463 and combination activity with relevant chemotherapy across multiple tumor types will be reported in an accompanying manuscript. 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. |
| Animal model | SCID-Beige Mice |
| Formulation & Dosage | Formulated in 5% DMSO, 10% EtOH, 20% Cremaphor ELP, and 65% D5W; 5 mg/kg; i.p. |
| References | ACS Med Chem Lett. 2014 Aug 26;5(10):1088-93; Sci Transl Med. 2015 Mar 18;7(279):279ra40; Molecular Cancer. 2015, 14(1):1-9. |
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