Sonidegib

製品コードS2151 バッチS215102

印刷

化学情報

Chemical Structure Synonyms NVP-LDE225, Erismodegib Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H26F3N3O3
分子量 485.5 CAS No. 956697-53-3
Solubility (25°C)* 体外 DMSO 97 mg/mL (199.79 mM)
Ethanol 97 mg/mL warmed with 50ºC water bath (199.79 mM)
Water 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Sonidegib is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. Phase 3.
in vitro Sonidegib (Erismodegib, NVP-LDE225) inhibits TM3 luciferized cell line with 0.6 nM and 8 nM, at the presence of 1 nM and 25 nM Hh agonist Ag1.5, respectively. [1]
in vivo Sonidegib (Erismodegib, NVP-LDE225) is highly bound to mouse, rat, and human plasma proteins (>99%) and moderately bound to dog and monkey plasma proteins (77 and 85%, respectively). LDE225 has high permeability (90.8% in man) in the PAMPA assay. LDE225 shows good oral bioavailability ranging from 69 to 102% in preclinical species when dosed in solution. LDE225 is a weak base with a measured pKa of 4.20 and exhibits relatively poor aqueous solubility. LDE225 demonstrates dose-related antitumor activity. At a dose of 5 mg/kg/day qd, LDE225 significantly inhibits tumor growth, corresponding to a T/C value of 33%. When dosed at 10 and 20 mg/kg/day qd, LDE225 gives rise to 51 and 83% regression, respectively. Gli1 mRNA inhibition correlates with tumor and plasma exposure of LDE225. LDE225 successfully penetrates the blood−brain barrier in tumor-bearing animals and results in tumor growth inhibition after 4 days of treatment. [1] LDE225 significantly reduces the tumor volume by 95.7% in Rip1-Tag2 mice. LDE225 prolongs survival in Rip1Tag2 mice. LDE225 decreases expression of stromal markers in the LDE225-treated mice. [2]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 TM3Hh12 cells
濃度 ~10 μM
反応時間 30 minutes
実験の流れ

LDE225 is prepared for assay by serial dilution in DMSO and then added to empty assay plates. TM3Hh12 cells (TM3 cells containing Hh-responsive reporter gene construct pTA-8xGli-Luc) are cultured in F12 Ham's/DMEM (1:1) containing 5% horse serum, 2.5% fetal bovine serum (FBS), and 15 mM HEPES, pH 7.3. Cells are harvested by trypsin treatment, resuspended in F12 Ham's/DMEM (1:1) containing 5% horse serum and 15 mM HEPES, pH 7.3, added to assay plates, and incubated with LDE225 for approximately 30 min at 37 °C in 5% CO2. Then 1 nM or 25 nM Ag1.5 is added to assay plates and incubated at 37 °C in the presence of 5% CO2. After 48 hours, either Bright-Glo or MTS reagent is added to the assay plates and luminescence or absorbance at 492 nm is determined. IC50 values, defined as the inflection point of the logistic curve, are determined by nonlinear regression of the Gli-driven luciferase luminescence or absorbance signal from MTS assay vs log10 (concentration) of LDE225 using the R statistical software pack
動物実験 動物モデル Orthotopic Ptch+/-p53-/- medulloblastoma allograft model in athymic nude mice
投薬量 40 mg/kg/day
投与方法 Administered via p.o. or b.i.d

カスタマーフィードバック

Data from [Data independently produced by Br J Cancer, 2014, 111(6), 1168-79]

Data from [Data independently produced by Br J Cancer, 2014, 111(6), 1168-79]

Data from [Nat Chem Biol, 2013, 9, 247-9]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells [ EBioMedicine, 2024, 101:105026] PubMed: 38417378
Hedgehog signalling is involved in acquired resistance to KRASG12C inhibitors in lung cancer cells [ Cell Death Dis, 2024, 15(1):56] PubMed: 38225225
Multiplatform molecular profiling uncovers two subgroups of malignant peripheral nerve sheath tumors with distinct therapeutic vulnerabilities [ Nat Commun, 2023, 14(1):2696] PubMed: 37164978
Selective induction of human renal interstitial progenitor-like cell lineages from iPSCs reveals development of mesangial and EPO-producing cells [ Cell Rep, 2023, S2211-1247(23)01614-5] PubMed: 38237600
Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2 [ Brain Pathol, 2023, 10.1111/bpa.13212] PubMed: 37721122
Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma [ Mol Cancer Ther, 2023, 22(3):343-356] PubMed: 36807728
Signaling Switching from Hedgehog-GLI to MAPK Signaling Potentially Serves as a Compensatory Mechanism in Melanoma Cell Lines Resistant to GANT-61 [ Biomedicines, 2023, 11(5)1353] PubMed: 37239024
Primary cilia support cartilage regeneration after injury [ Int J Oral Sci, 2023, 15(1):22] PubMed: 37268650
Single-cell analysis reveals distinct fibroblast plasticity during tenocyte regeneration in zebrafish [ Sci Adv, 2023, 9(46):eadi5771] PubMed: 37967180
Methacrylic acid-based biomaterials promote peripheral innervation in the subcutaneous space of mice [ Biomaterials, 2022, 289:121764] PubMed: 36067565

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。

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