Lanraplenib (GS-SYK)

製品コードS9715 バッチS971501

印刷

化学情報

Synonyms

GS-9876

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₃H₂₅N₉O

分子量

443.50

CAS No.

1800046-95-0

Solubility (25°C)*

体外

DMSO

89 mg/mL (200.67 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）

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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.25mg/ml (0.56mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.25mg/ml (0.56mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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	Lanraplenib (GS-SYK) は、IC50 が 9.5 nM の、強力で選択性が高く、経口活性のある Spleen Tyrosine Kinase (SYK) 阻害剤です。Lanraplenib は、サルまたはヒトにおいて出血時間 (BT) を延長することなく、glycoprotein VI (GPVI) receptor を介して血小板の SYK 活性を阻害します。
in vitro	Lanraplenib (GS-SYK) inhibits anti-IgM stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells with EC50 values of 24–51 nM. Functionally, it inhibits anti-IgM mediated CD69 and CD86 expression on B-cells (EC50=112±10 nM and 164±15 nM, respectively) and anti-IgM /anti-CD40 co-stimulated B cell proliferation (EC50=108±55 nM). In human macrophages, this compound inhibits IC-stimulated TNFα and IL-1β release (EC50=121±77 nM and 9±17 nM, respectively). Anti-CD3/anti-CD28 stimulated T cell proliferation is weakly inhibited (EC50=1291±398 nM), with selectivity >10-fold versus the inhibition of B cell proliferation. In human blood, it blocks SYK phosphorylation, CD69 expression on B cells, and CD63 expression in basophils. Additionally, it inhibits glycoprotein VI (GPVI)-induced phosphorylation of linker for activation of T cells and phospholipase Cγ2, platelet activation and aggregation in human whole blood, and platelet binding to collagen under arterial flow.
in vivo	Lanraplenib (GS-SYK) demonstrates a dose-dependent improvement in clinical score and histopathology parameters with once-daily dosing in short and long term rat models of collagen-induced arthritis (CIA). Significant efficacy can be achieved with this compound at doses that produce trough pSYK inhibition of <50%. Ex vivo, GPVI-stimulated platelet aggregation is inhibited in it-treated monkeys without a concomitant increase in bleeding time (BT). Similarly, orally administered GS-9876 does not increase BT in humans.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Human blood platelets
	濃度	0.01 μM to 100 μM
	反応時間	15 min
	実験の流れ	Blood is preincubated for 15 min with Lanraplenib (GS-SYK) and activated with ADP (0.2 μM) or convulxin (30 ng/mL) for 2 min at room temperature. After this incubation, samples are stained for CD61 and CD62P, fixed, and analyzed on a FACSCanto II flow cytometer. The percentages of CD62P+ platelets are quantified and the values are subjected to nonlinear regression analysis using Prism 6 to generate EC50 values.
動物実験	動物モデル	female cynomolgus monkeys
	投薬量	5 mg/kg, 15 mg/kg, 45 mg/kg
	投与方法	Oral gavage

参考

https://ard.bmj.com/content/75/Suppl_2/443.3
https://pubmed.ncbi.nlm.nih.gov/30172129/

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：

BTN2A1 targeting reprograms M2-like macrophages and TAMs via SYK and MAPK signaling [ Cell Rep, 2024, 43(10):114773]	PubMed: 39325623
Platelet spleen tyrosine kinase is a key regulator of anti-PF4 antibody-induced immunothrombosis [ Blood Adv, 2024, bloodadvances.2024014167]	PubMed: 39705541
A high-content microscopy drug screening platform for regulators of the extracellular digestion of lipoprotein aggregates by macrophages [ bioRxiv, 2024, 2024.09.26.615160]	PubMed: 39605493

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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