dBET1

製品コードS8296 バッチS829601

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₃₈H₃₇ClN₈O₇S
	分子量	785.27	CAS No.	1799711-21-9
Solubility (25°C)*	体外	DMSO	100 mg/mL (127.34 mM)
		Ethanol	39 mg/mL (49.66 mM)
		Water	˂1 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	dBET1 is a CRBN-based BET degrader with an IC50 of 20 nM, showing highly selectivity. Out of 7,429 proteins, only the expression of the oncoproteins MYC and PIM1, as well as BRD2, BRD3 and BRD4 are significantly downregulated by dBET1 treatment.
in vitro	Treatment with dBET1 elicits a comparable, modest effect on MYC and PIM1 expression. Its treatment downregulates MYC and PIM1 transcription, suggestive of secondary transcriptional effects and transcription of BRD4 and BRD3 are unaffected, consistent with post-transcriptional effects. Transcription of BRD2 is affected by dBET1 and protein stability of the BRD2 gene product is influenced by dBET1. dBET1 induces a potent and superior inhibitory effect on MV4;11 cell proliferation at 24 hours (measured by ATP content, IC50 = 0.14 μM). Exposure of primary leukemic patient blasts to dBET1 elicits dose-proportionate depletion of BRD4 and induction of apoptosis^[1]. dBET1-mediated targeted degradation of BET proteins robustly dampens pro-inflammatory responses in LPS-stimulated microglia, that is, depletion of BRD2 and BRD4 with dBET1 is associated with dramatically reduced LPS-induced COX-2 and iNOS protein levels and pro-inflammatory gene transcription of Nos2, Il-1β, Il-6, Tnfα, Ccl2, Ptgs2, and Mmp9^[2].
in vivo	Administration of dBET1 attenuates tumor progression and decreases tumor weight assessed post-mortem in murine xenograft model of human MV4;11 leukemia cells. Pharmacokinetic studies of dBET1 (50 mg/kg IP) corroborate adequate drug exposure in vivo (Cmax = 392 nM, Tmax=0.5 hr, terminal t_1/2=6.69 hr, AUC_last=2109 hrng/ml, AUC_INF=295 hrng/ml). Two weeks of dBET1 is well tolerated by mice without a meaningful effect on weight, white blood count, hematocrit or platelet count^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	SUM149 cells
	濃度	'0.1, 0.5, 1, 5, 10 μM
	反応時間	18 h
	実験の流れ	Immunoblot analysis
動物実験	動物モデル	Murine xenograft model of human MV4;11 leukemia cells (CD1 mice)
	投薬量	50 mg/kg daily
	投与方法	i.p.

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：

BRD2 protects the rat H9C2 cardiomyocytes from hypoxia‑reoxygenation injury by targeting Nrf2/HO‑1 signaling pathway [ Exp Ther Med, 2023, 10.3892/etm.2023.12241]	PubMed: 37869639
BRD2 protects the rat H9C2 cardiomyocytes from hypoxia‑reoxygenation injury by targeting Nrf2/HO‑1 signaling pathway [ Exp Ther Med, 2023, 26(5):542]	PubMed: 37869639
Protein Ligand Interactions Using Surface Plasmon Resonance [ Methods Mol Biol, 2021, 2365:3-20]	PubMed: 34432236

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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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