Nilotinib

製品コードS1033 バッチS103308

化学情報

	Synonyms	AMN-107	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₈H₂₂F₃N₇O
	分子量	529.52	CAS No.	641571-10-0
Solubility (25°C)*	体外	DMSO	35 mg/mL (66.09 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Nilotinib is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.
in vitro	Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induces apoptosis of HSCs, which is correlated with reduced bcl-2 expression, increases p53 expression, cleavage of PARP, as well as increases expression of PPARγ and TRAIL-R. Nilotinib also induces cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1. Interestingly, Nilotinib not only inhibits activation of PDGFR, but also TGFRII through Src. Nilotinib significantly inhibits PDGF and TGFβ-simulated phosphorylation of ERK and Akt. Furthermore, PDGF- and TGFβ-activated phosphorylated form(s) of Abl in human HSCs are inhibited by Nilotinib. ^[2] Nilotinib inhibits most imatinib-resistant Bcr-Abl mutations, except for T315I. ^[3] Nilotinib inhibits PDGF-DD-mediated ERK1/2 activation, basal and PDGF-DD-mediated activation of PDGFRβ and Akt, and schwannoma proliferation. Nilotinib is more potent than imatinib, exerting its maximal inhibitory effect at concentrations lower than steady-state trough plasma levels. ^[4] Nilotinib also significantly reduces the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Nilotinib treatment also significantly inhibits the PDGF-induced proliferation of lung fibroblasts. ^[5] Nilotinib inhibits the proliferation of Ba/F3 cells expressing p210- and p190-Bcr-Abl, or K562 and Ku-812F cells with IC50 values ≤12 nM. ^[6]
in vivo	Nilotinib reduces collagen deposition and α-SMA expression in CCl₄ and BDL-induced fibrosis. Nilotinib could induce HSC undergoing apoptosis, which is correlated with downregulation of bcl-2. ^[2] Nilotinib attenuates the extent of lung injury and fibrosis. Nilotinib therapy significantly reduces the levels of hydroxyproline on days 14 and 21, which is accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFRβ. ^[5] AMN107 prolongs survival of mice injected with Bcr-Abl-transformed hematopoietic cell lines or primary marrow cells, and prolongs survival in imatinib-resistant CML mouse models. ^[6]
特徴	A selective inhibitor of native and mutant Bcr-Abl.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Human primary Schwann and schwannoma cells
	濃度	1-10 μM
	反応時間	72 hours
	実験の流れ	Human primary Schwann and schwannoma cells are seeded on precoated 96-well plates. Nilotinib is added 40 minutes before stimulation with 100 ng/mL PDGF-DD, and cells are cultured for 72 hours (3 days). Because the half-life of Nilotinib is 18 hours, one-half of the originally added concentrations are added freshly every day. In addition to DAPI staining and determination of the total cell number, the more sensitive and accurate BrdU incorporation method is used to detect proliferating cells. Total cell amount (DAPI) and number of dividing cells (BrdU-positive) are blindly counted using an inverted fluorescent microscope and 200 × magnification. All cells in every well are counted. The total cell number per well differed between various cell batches and is 100–300 cells/well.
動物実験	動物モデル	Systemic 32D Bcr-Abl leukemia model in Female BALB/c mice, Bioluminescent Bcr-Abl model of CML in Female NOD-SCID mice and Bone marrow transplant Bcr-Abl model of CML in syngeneic Balb/c recipient mice
	投薬量	75 mg/kg, 100 mg/kg
	投与方法	Oral administration

参考

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カスタマーフィードバック

: Data from [Molecules, 2014, 19, 3356-75]

: Data from [Urol Oncol, 2014, 0.1016/j.urolonc.2014.06.001]

: Data from [Urol Oncol, 2014, 0.1016/j.urolonc.2014.06.001]

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：

Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease [ Nat Commun, 2024, 15(1):651]	PubMed: 38246924
Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089]	PubMed: 38453961
The molecular basis of Abelson kinase regulation by its αI-helix [ Elife, 2024, 12RP92324]	PubMed: 38588001
Satellite cell-derived TRIM28 is pivotal for mechanical load- and injury-induced myogenesis [ EMBO Rep, 2024, 10.1038/s44319-024-00227-1]	PubMed: 39143258
Regulation of Cell Cycle Progression through RB Phosphorylation by Nilotinib and AT-9283 in Human Melanoma A375P Cells [ Int J Mol Sci, 2024, 25(5)2956]	PubMed: 38474202
Asciminib Maintains Antibody-Dependent Cellular Cytotoxicity against Leukemic Blasts [ Cancers (Basel), 2024, 16(7)1288]	PubMed: 38610966
Identification of aryl hydrocarbon receptor allosteric antagonists from clinically approved drugs [ Drug Dev Res, 2024, 85(5):e22232]	PubMed: 38992915
Mutation and cell state compatibility is required and targetable in Ph+ acute lymphoblastic leukemia minimal residual disease [ bioRxiv, 2024, 2024.06.06.597767]	PubMed: 38915726
Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia [ Mol Cancer, 2023, 10.1186/s12943-023-01837-4]	PubMed: 37932786
Promoter swapping of truncated PDGFRB drives Ph-like acute lymphoblastic leukemia [ NPJ Precis Oncol, 2023, 7(1):132]	PubMed: 38071343

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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