JQ1

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

(+)-JQ-1 (JQ1) 是一种有效、选择性、细胞渗透性 BET bromodomain 抑制剂，对 BRD4 BD1 和 BD2 的 IC50 分别为 77 nM/33 nM。

(+)-JQ-1 (JQ1) is a potent, selective, cell-permeable BET bromodomain inhibitor with IC50 of 77 nM/33 nM for BRD4 BD1 and BD2, respectively; induces rapid expression of keratin in treated NMC 797 cells, displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models.(In Vitro):(+)-JQ-1 represents a potent, highly specific and Kac competitive inhibitor for the BET family of bromodomains. (+)-JQ-1 (100 nM, 48 h) prompts squamous differentiation exhibited by cell spindling, flattening and increased expression of keratin. (+)-JQ-1 (250 nM) induces rapid expression of keratin in treated NMC 797 cells compared to (-)-JQ1 (250 nM) and vehicle controls, as determined by quantitative immunohistochemistry.(+)-JQ-1 (250 nM) elicits a time-dependent induction of strong (3+) keratin staining of treated NMC 797 cells, compared to (-)-JQ1 (250 nM). De-repression of autophagy genes is observed almost immediately after (+)-JQ-1 addition. (+)-JQ-1 is a potent thienodiazepine inhibitor (Kd=90 nM) of the BET family coactivator protein BRD4, which is implicated in the pathogenesis of cancer via transcriptional control of the MYC oncogene. Dose-ranging studies of (+)-JQ-1 demonstrates potent inhibition of H4Kac4 binding with a IC50 value of 10 nM for murine BRDT and 11 nM for human BRDT. (In Vivo):Matched cohorts of mice with established tumors are randomized to treatment with (+)-JQ1 (50 mg/kg) or vehicle, administered by daily intraperitoneal injection. Prior to randomization, and after four days of therapy, mice are evaluated by FDG-PET imaging. A marked reduction in FDG uptake is observed with (+)-JQ1 treatment. Tumor-volume measurements confirm a reduction in tumor growth with JQ1 treatment. Pharmacokinetic studies of (+)-JQ1 are performed in CD1 mice following intravenous and oral administration. Mean plasma concentration-time profiles of (+)-JQ1 after intravenous dosing (5 mg/kg). The pharmacokinetic parameters for intravenous (+)-JQ1 demonstrate excellent drug exposure (AUC=2090 hr*ng/mL) and an approximately one hour half-life (T1/2). Mean plasma concentration-time profiles of (+)-JQ1 after oral dosing (10 mg/kg). The pharmacokinetic parameters for oral (+)-JQ1 demonstrate excellent oral bioavailability (F=49%), peak plasma concentration (Cmax=1180 ng/mL) and drug exposure (AUC=2090 hr*ng/mL).

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JQ-1 | (+)-JQ-1

Chromatin/Epigenetic

Bromodomain

BRD4(1)|BRD4(2)

Cancer

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1268524-70-4

456.9882

C23H25ClN4O2S

>98% (HPLC)

DMSO: ≥ 45 mg/mL

O=C(OC(C)(C)C)C[C@H]1C2=NN=C(C)N2C3=C(C(C)=C(C)S3)C(C4=CC=C(Cl)C=C4)=N1

6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-trimethyl-, 1,1-dimethylethyl ester, (6S)-

(-20℃)

With Ice Pack

≥ 2 years