SNS-032 (BMS-387032)

製品コードS1145 バッチS114501

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₇H₂₄N₄O₂S₂
	分子量	380.53	CAS No.	345627-80-7
Solubility (25°C)*	体外	DMSO	76 mg/mL (199.72 mM)
		Ethanol	30 mg/mL (78.83 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	SNS-032 (BMS-387032) has firstly been described as a selective inhibitor of CDK2 with IC50 of 48 nM in cell-free assays and is 10- and 20-fold selective over CDK1/CDK4. It is also found to be sensitive to CDK7/9 with IC50 of 62 nM/4 nM, with little effect on CDK6. SNS-032 (BMS-387032) induces apoptosis.
in vitro	SNS-032 has low sensitivity to CDK1 and CDK4 with IC50 of 480 nM and 925 nM, respectively. SNS-032 effectively kills chronic lymphocytic leukemia cells in vitro regardless of prognostic indicators and treatment history. Compared with flavopiridol and roscovitine, SNS-032 is more potent, both in inhibition of RNA synthesis and at induction of apoptosis. SNS-032 activity is readily reversible; removal of SNS-032 reactivates RNA polymerase II, which led to resynthesis of Mcl-1 and cell survival. ^[1] SNS-032 inhibits three dimensional capillary network formations of endothelial cells. SNS-032 completely prevents U87MG cell–mediated capillary formation of HUVECs. In addition, SNS-032 significantly prevents the production of VEGF in both cell lines, SNS-032 prevents in vitro angiogenesis, and this action is attributable to blocking of VEGF. Preclinical studies have shown that SNS-032 induces cell cycle arrest and apoptosis across multiple cell lines. ^[2] SNS-032 blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. SNS-032 activity is unaffected by human serum. ^[3] SNS-032 induces a dose-dependent increase in annexin V staining and caspase-3 activation. At the molecular level, SNS-032 induces a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and inhibits the expression of CDK2 and CDK9 and dephosphorylated CDK7. ^[4]
in vivo	SNS-032 prevents tumor cell-induced VEGF secretion in a tumor coculture model. ^[2] SNS-032, a new CDK inhibitor, is more selective and less cytotoxic and has been shown to prolong stable disease in solid tumors. ^[4]

製品説明

SNS-032 (BMS-387032) has firstly been described as a selective inhibitor of CDK2 with IC50 of 48 nM in cell-free assays and is 10- and 20-fold selective over CDK1/CDK4. It is also found to be sensitive to CDK7/9 with IC50 of 62 nM/4 nM, with little effect on CDK6. SNS-032 (BMS-387032) induces apoptosis.

in vitro

SNS-032 has low sensitivity to CDK1 and CDK4 with IC50 of 480 nM and 925 nM, respectively. SNS-032 effectively kills chronic lymphocytic leukemia cells in vitro regardless of prognostic indicators and treatment history. Compared with flavopiridol and roscovitine, SNS-032 is more potent, both in inhibition of RNA synthesis and at induction of apoptosis. SNS-032 activity is readily reversible; removal of SNS-032 reactivates RNA polymerase II, which led to resynthesis of Mcl-1 and cell survival. ^[1]

SNS-032 inhibits three dimensional capillary network formations of endothelial cells. SNS-032 completely prevents U87MG cell–mediated capillary formation of HUVECs. In addition, SNS-032 significantly prevents the production of VEGF in both cell lines, SNS-032 prevents in vitro angiogenesis, and this action is attributable to blocking of VEGF. Preclinical studies have shown that SNS-032 induces cell cycle arrest and apoptosis across multiple cell lines. ^[2]

SNS-032 blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. SNS-032 activity is unaffected by human serum. ^[3]

SNS-032 induces a dose-dependent increase in annexin V staining and caspase-3 activation. At the molecular level, SNS-032 induces a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and inhibits the expression of CDK2 and CDK9 and dephosphorylated CDK7. ^[4]

in vivo

SNS-032 prevents tumor cell-induced VEGF secretion in a tumor coculture model. ^[2]

SNS-032, a new CDK inhibitor, is more selective and less cytotoxic and has been shown to prolong stable disease in solid tumors. ^[4]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	HUVECs and U87MG cells
	濃度	0–0.5 mM
	反応時間	24, 48, or 72 hours
	実験の流れ	Cell Titer-Glo (CTG) luminescent assay is performed to measure the growth curves of both HUVECs and U87MG cells. U87MG cells and HUVECs (2×10³ cells/well) are seeded in a 96-well microplate in a final volume of 100 ml. After 24 hours, cells are treated with various doses of SNS-032 (0–0.5 mM) for 24, 48, or 72 hours. After completion of the treatment, 100 ml of CTG solution is added to each well and incubated for 20 minutes at room temperature in the dark. Lysate (50 ml) is transferred to a 96-well white plate, and luminescence is measured by POLARstar OPTIMA. Percent cell growth is calculated by considering 100% growth at the time of SNS-032 addition.
動物実験	動物モデル	Nude nu/nu BALB/c mice
	投薬量	15 mg/kg
	投与方法	i.p.

参考

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カスタマーフィードバック

: Data from [Data independently produced by Cell Death Differ, 2014, 21(3), 491-502]

: , , Dr. Yong-Weon Yi from Georgetown University Medical Center

: , , Yolanda Sanchez from Geisel School of Medicine at Dartmouth

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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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