BiochemProbe — Life Science Research Reagents

JQ-1 free base · Synonyms: JQ1

-JQ-1, a chemical probe, is a potent, specific, CNS-penetrant and reversible BET bromodomain inhibitor.

For research use only. Not for human or veterinary use.

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JQ-1 structure

CAS No.: 1268524-70-4

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
500 mg USD 498.00 BP-02472-500mg In stock Get quote
1 g USD 796.00 BP-02472-1g In stock Get quote
2 g USD 1,274.00 BP-02472-2g In stock Get quote
3 g USD 1,520.00 BP-02472-3g In stock Get quote
5 g USD 2,040.00 BP-02472-5g In stock Get quote
10 g USD 3,260.00 BP-02472-10g In stock Get quote

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Description

(+)-JQ-1 (JQ1), a chemical probe, is a potent, specific, CNS-penetrant and reversible BET bromodomain inhibitor, with IC50s of 77 and 33 nM for the first and second bromodomain (BRD4(1/2)) . (+)-JQ-1 also activates autophagy .

Biological activity

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)[1]. De-repression of autophagy genes is observed almost immediately after (+)-JQ-1 addition[2]. (+)-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(1) and 11 nM for human BRDT(1). 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).

Identifiers

SMILES
CC1=NN=C2[C@H](CC(=O)OC(C)(C)C)N=C(C3=C(SC(C)=C3C)N12)C1=CC=C(Cl)C=C1
InChIKey
DNVXATUJJDPFDM-KRWDZBQOSA-N

Specifications

MW (average)
456.9880
Formula
C23H25ClN4O2S
CAS No.
1268524-70-4
Physical state
Solid
Color
White to yellow
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
Powder -20°C, 3 years , 4°C, 2 years ; In solvent -20°C, 6 months;

Solubility

Soluble in DMSO

Documents

References

[1]. Filippakopoulos P, et al. Selective inhibition of BET bromodomains. Nature. 2010 Dec 23;468(7327):1067-73.
[2].Sakamaki JI, et al. Bromodomain Protein BRD4 Is a Transcriptional Repressor of Autophagy and LysosomalFunction. Mol Cell. 2017 May 18;66(4):517-532.e9.
[3].Matzuk MM, et al. Small-molecule inhibition of BRDT for male contraception. Cell. 2012 Aug 17;150(4):673-84.
[4].Zhong X, et al. JQ1 attenuates neuroinflammation by inhibiting the inflammasome-dependent canonical pyroptosis pathway in SAE. Brain Res Bull. 2022 Oct 15;189:174-183.

Same research area

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