Lanraplenib (GS-SYK)

製品コードS9715 バッチS971501

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
* <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) is a potent, highly selective and orally active inhibitor of Spleen Tyrosine Kinase (SYK) with IC50 of 9.5 nM. Lanraplenib inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans.
in vitro	GS-9876 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, GS-9876 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, GS-9876 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, GS-9876 blocks SYK phosphorylation, CD69 expression on B cells, and CD63 expression in basophils.^[1] GS-9876 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.^[2]
in vivo	GS-9876 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 GS-9876 doses that produces trough pSYK inhibition of <50%.^[1] Ex vivo, GPVI-stimulated platelet aggregation is inhibited in GS-9876-treated monkeys without a concomitant increase in bleeding time (BT). Similarly, orally administered GS-9876 does not increase BT in humans.^[2]

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-9876) and activated with ADP (0.2 μM) or convulxin (30 ng/mL) for 2 min at room temperature. 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

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

BTN2A1 targeting reprograms M2-like macrophages and TAMs via SYK and MAPK signaling [ Cell Rep, 2024, 43(10):114773]

PubMed: 39325623

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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