受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C29H37N5O3 |
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分子量 | 503.64 | CAS No. | 1149705-71-4 | ||||
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (198.55 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <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. |
製品説明 | XL888 is an ATP-competitive inhibitor of HSP90 with IC50 of 24 nM. Phase 1. |
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in vitro | XL888 induces HER2 degradation in NCI-N87 cells with IC50 of 56 nM. XL888 inhibits the proliferation of HER2 over-expressed NCI-N87, HER2 over-expressed BT-474, HER2 over-expressed MDA-MB-453, MET mutated MKN45, B-Raf mutated Colo-205, B-Raf mutated SK-MEL-28, EGFR mutated HN5, EGFR mutated NCI-H1975, PI3K mutated MCF7, and K-Ras mutated A549 with IC50 of 21.8, 0.1, 16.0, 45.5, 11.6, 0.3, 5.5, 0.7, 4.1 and 4.3 nM. [1] XL888 leads to dose-dependent decreases in the growth of vemurafenib-naive and vemurafenib-resistant melanoma cell lines and melanoma cell lines with intrinsic resistance with IC50 of all around 0.1 μM. The growth inhibitory effects of XL888 are associated with induction of either a G1-phase cell-cycle arrest (WM164, M229, M229R, M249, M249R, 1205Lu, and WM39 cell lines) or a G2-M phase cell-cycle arrest (WM164R, 1205LuR, and RPMI 7951 cell lines). XL888 (300 nmol) induces high levels ( > 66%) of apoptosis, and loss of mitochondrial membrane potential (TMRM) in these cell lines. The cytotoxic effects of XL888 are durable with no signs of colony formation observed in any of the cell lines even cultured up to 4 weeks. XL888 treatment (300 nM, 48 hours) leads to the degradation of IGF1R, PDGFRβ, ARAF, CRAF, and cyclin D1 and the inhibition of AKT, ERK, and S6 signaling in all of the cell lines with acquired BRAF inhibitor resistance. treatment of cell lines that are naive, intrinsically resistant, and with acquired vemurafenib resistance. Treatment with XL888 (300 nM) leads to robust time-dependent increases in the expression of HSP70 isoform 1. XL888 (48 hours, 300 nM) treatment increases the expression of BIM-EL, BIM-L, and BIM-S expression in the M229R, 1205LuR, RPMI7951, and WM39 cell lines, induces expression of BIM-L and BIM-S in the WM164R cell line, and BIM-EL in the M249R cell line. [2] |
in vivo | XL888 (100 mg/kg) significantly induces the regression of, or growth inhibition (50%) of established M229R and 1205LuR xenografts in SCID mice. 15 days of XL888 treatment showes a robust (8.6-fold) increase in intratumoral HSP70 expression compared with controls. XL888 treatment is noted to be proapoptotic in vivo and leads to increased TUNEL staining in M229R xenografts associated with increased expression of BIM and decreased expression of Mcl-1. [2] |
細胞アッセイ | 細胞株 | 1205Lu melanoma cells lines |
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濃度 | ~10 μM | |
反応時間 | 3 days | |
実験の流れ | Cells are plated at a density of 2?05 per mL and left to grow overnight before being treated with increasing concentrations of XL888. After incubation with XL888 for 3 days, Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays are performed. | |
動物実験 | 動物モデル | Melanoma carcinoma xenografts 1205Lu |
投薬量 | 100 mg/kg | |
投与方法 | 3 times per week by oral gavage |
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Data from [Data independently produced by , , Clin Cancer Res, 2012, 18(9):2502-2514.]
BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability [ Sci Adv, 2023, 9(35):eade7486] | PubMed: 37656784 |
deepOrganoid: A brightfield cell viability model for screening matrix-embedded organoids [ SLAS Discov, 2022, 27(3):175-184] | PubMed: 35314378 |
In Vivo Conformational Dynamics of Hsp90 and Its Interactors [ Cell Chem Biol, 2016, 23(6):716-26] | PubMed: 27341434 |
Reactivation of ERK and Akt confers resistance of mutant BRAF colon cancer cells to the HSP90 inhibitor AUY922. [ Oncotarget, 2016, 7(31):49597-49610] | PubMed: 27391062 |
The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. [Paraiso KH, et al. Clin Cancer Res, 2012, 18(9):2502-14] | PubMed: 22351686 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。