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Purity: ≥98%
(+)-JQ1 is a novel, potent and highly specific BET (Bromodomain and extra terminal domain) bromodomain inhibitor with antineoplastic activity. It inhibits BRD4(1/2) with an IC50 of 77 nM and 33 nM in enzymatic assays. It has high specificity for BET in that it only binds to bromodomains of the BET family, but not to any bromodomains of non-BET family. (+)-JQ1 has potential antineoplastic activity against various cancers such as MM (Multiple myeloma), pancreatic ductal adenocarcinoma and ovarian cancer etc. Its mechanism of action is to inhibit c-MYC and upregulate p21. (+)-JQ1 has been used as a chemical probe to investigate the role of BET bromodomains in the transcriptional regulation of oncogenesis.
| ln Vitro |
(+)-JQ-1 represents a strong, highly selective and Kac-competitive inhibitor of the bromodomain BET family. (+)-JQ-1 (100 nM, 48 h) increases squamous development, evidenced by cell spindle formation, flattening, and enhanced keratin expression. (+)-JQ-1 (250 nM) stimulates fast expression of keratin in treated NMC 797 cells compared to (-)-JQ1 (250 nM) and vehicle control, as evaluated by quantitative immunohistochemistry of. (+)-JQ-1 (relative to (-)-JQ1 (250 nM)) causes time-dependent strong (3+) keratin staining in treated NMC 797 cells [1]. Derepression of autophagy genes was seen almost immediately upon addition of (+)-JQ-1 [2]. (+)-JQ-1 is a strong thiophenediazepine inhibitor (Kd=90 nM) of the BET family coactivator protein BRD4, which participates in the development of cancer through the transcriptional regulation of the MYC oncogene. Dose-ranging experiments of (+)-JQ-1 indicated efficient suppression of H4Kac4 binding, with IC50 values of 10 nM for mouse BRDT (1) and 11 nM for human BRDT (1) [3].
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| ln Vivo |
Matching mouse cohorts with tumors that had already developed were randomized to receive intraperitoneal injections of either vehicle or (+)-JQ1 (50 mg/kg) every day. FDG-PET imaging was used to assess the mice both four days post-treatment and before to randomization. FDG uptake was shown to be significantly reduced when (+)-JQ1 was administered. Tumor growth was inhibited by JQ1 treatment, as demonstrated by assessments of tumor volume. CD1 mice were used for pharmacokinetic studies of (+)-JQ1 following oral and intravenous dosing. Time profile of the mean plasma concentration of (+)-JQ1 following intravenous injection (5 mg/kg). The half-life (T1/2) of intravenous (+)-JQ1 was approximately one hour, and its pharmacokinetic characteristics demonstrated good drug exposure (AUC=2090 hr*ng/mL). After oral dosage (10 mg/kg), a mean plasma concentration-time profile of (+)-JQ1 was created. Oral (+)-JQ1 pharmacokinetic parameters showed good drug exposure (AUC=2090 hr*ng) /mL), peak plasma concentration (Cmax=1180 ng/mL), and oral bioavailability (F=49%)[1].
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| 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 |
| Molecular Formula |
C23H25CLN4O2S
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| Molecular Weight |
456.99
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| CAS # |
1268524-70-4
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| Related CAS # |
(R)-(-)-JQ1 Enantiomer;1268524-71-5;JQ-1 (carboxylic acid);202592-23-2
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| SMILES |
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
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1882 mL | 10.9412 mL | 21.8823 mL | |
| 5 mM | 0.4376 mL | 2.1882 mL | 4.3765 mL | |
| 10 mM | 0.2188 mL | 1.0941 mL | 2.1882 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Leukemia and lymphoma cell lines are broadly sensitive to BET-bromodomain inhibition.Proc Natl Acad Sci U S A.2011 Oct 4;108(40):16669-74. |
Gene expression profiling of LP-1 and Raji cells treated with active or inactive BET inhibitors.Proc Natl Acad Sci U S A.2011 Oct 4;108(40):16669-74. |
Small molecule BET-bromodomain inhibition suppressesMYCtranscription.Proc Natl Acad Sci U S A.2011 Oct 4;108(40):16669-74. |
MYC reconstitution significantly protects cells from BET-mediated effects.Proc Natl Acad Sci U S A.2011 Oct 4;108(40):16669-74. |
BET-bromodomain inhibition decreases tumor load in vivo.Proc Natl Acad Sci U S A.2011 Oct 4;108(40):16669-74. |
Integrated genomic rationale for BET bromodomains as therapeutic targets in MM.Cell.2011 Sep 16;146(6):904-17. |
Inhibition of Myc-dependent transcription by theJQ1BET bromodomain inhibitor.Cell.2011 Sep 16;146(6):904-17. |
BET inhibition suppressesMYCtranscription in MM.Cell.2011 Sep 16;146(6):904-17. |
Regulation ofMYCtranscription by BET bromodomains.Cell.2011 Sep 16;146(6):904-17. |
Anti-myeloma activity ofJQ1in vitro.Cell.2011 Sep 16;146(6):904-17. |
JQ1induces cell cycle arrest and cellular senescence in MM cells.Cell.2011 Sep 16;146(6):904-17. |
Translational implications of BET bromodomain inhibition in MM.Cell.2011 Sep 16;146(6):904-17. |
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