Uzansertib (INCB053914)

製品コードS8800 バッチS880001

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₆H₂₆F₃N₅O₃.H₃O₄P

分子量

611.51

CAS No.

2088852-47-3

Solubility (25°C)*

体外

DMSO

50 mg/mL (81.76 mM)

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <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	ウザンセルチブ（INCB053914）は、新規のATP競合型小分子であり、生化学アッセイにおいてPIM1、PIM2、PIM3に対しそれぞれ0.24 nM、30 nM、0.12 nMのIC50値を示すPIMキナーゼの汎阻害剤です。
in vitro	Uzansertib (INCB053914) potently inhibits the activities of all three PIM isozymes with half maximal inhibitory concentration (IC50) values in the order of PIM1 ≈ PIM3 < PIM2. It is highly selective against a panel of more than 50 kinases (>475-fold selectivity), except for RSK2 for which this compound has modest potency (IC50 = 7.1 μM). No kinase other than Per-Arnt-Sim (PAS) kinase is significantly inhibited by INCB053914 (100 nM). In cell proliferation assays, it is active as a single agent in the majority of cell lines derived from different hematological malignancies, including MM, AML, DLBCL, MCL and T-ALL, with IC50 values ranging from 3-300 nM. This compound synergizes with a variety of cytotoxic and targeted agents, reducing the viability of a panel of hematological tumor cell lines.
in vivo	In vivo, single-agent Uzansertib (INCB053914) inhibits Bcl-2-associated death promoter protein phosphorylation and dose-dependently inhibited tumor growth in acute myeloid leukemia and multiple myeloma xenografts. It inhibits tumor growth in a dose-dependent manner in mice bearing MOLM-16 (AML) or KMS-12-BM (MM) tumors. A pharmacokinetic analysis of plasma concentrations of this compound up to 16 hours post oral administration in MOLM-16 and KMS-12-BM tumor-bearing mice suggests dose proportionality.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MOLM-16 (AML), Pfeiffer (DLBCL), KMS-12-PE (MM), and KMS-12-BM (MM) cells
	濃度	0-1 μM
	反応時間	2 h
	実験の流れ	MOLM-16 (AML), Pfeiffer (DLBCL), KMS-12-PE (MM), and KMS-12-BM (MM) cells (10⁶) are incubated with Uzansertib (INCB053914) at concentrations ranging from 0 (phosphate-buffered saline [PBS]) to 1 μM for 2 hours in RPMI medium. Cells are centrifuged at 1,000 rpm for 10 minutes and lysed with 1× lysis buffer supplemented with 1 mM phenylmethane sulfonyl fluoride and proteinase inhibitor cocktail. Cell lysates are stored at -80°C before determining phosphoprotein and PIM2 levels by Western blotting.
動物実験	動物モデル	Human MOLM-16 (AML) and KMS-12-BM (MM) xenografts established in SCID mice
	投薬量	0-100 mg/kg
	投与方法	by oral gavage

参考

https://pubmed.ncbi.nlm.nih.gov/29927999/
http://cancerres.aacrjournals.org/content/75/15_Supplement/5397

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：

Inhibition of Pim kinases triggers a broad antiviral activity by affecting innate immunity and via the PI3K-Akt-mTOR axis the endolysosomal system [ Antiviral Res, 2024, 226:105891]	PubMed: 38649071
Human papillomavirus insertions identify the PIM family of serine/threonine kinases as targetable driver genes in head and neck squamous cell carcinoma. [ Cancer Lett, 2020, 476:23-33]	PubMed: 31958486
RNA-Seq analysis reveals that spring viraemia of carp virus induces a broad spectrum of PIM kinases in zebrafish kidney that promote viral entry. [ Fish Shellfish Immunol, 2020, 99:86-98]	PubMed: 32004617

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。