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Purity: ≥98%
(-)-JQ-1 is the (R)-Enantiomer of JQ1 or the stereoisomer of (+)-JQ1. While (+)-JQ1 has an IC50 of 77 nM and 33 nM for BRD4(1/2) in enzymatic assays, it is a potent and extremely specific BET (Bromodomain and extra terminal domain) bromodomain inhibitor. No bromodomains interact significantly with ()-JQ1. Additionally, the ()-JQ1 enantiomer is relatively inactive in nuclear protein in testis (NUT) midline carcinoma (NMC). In that it only binds to bromodomains from the BET family and not any other bromodomains, (+)-JQ1 has high specificity for BET. (+)-JQ1 may have anti-cancer properties against a number of cancers, including Multiple Myeloma (MM), Pancreatic Ductal Adenocarcinoma, and Ovarian Cancer. It functions by inhibiting c-MYC and increasing p21. In order to learn more about the function of BET bromodomains in the transcriptional control of oncogenesis, (+)-JQ1 was used as a chemical probe.
| Targets |
BRD4 (IC50 = 33 nM); BRD4 (IC50 = 77 nM)
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| ln Vitro |
(+)-JQ1 enantiomer binds directly into the Kac binding site of BET bromodomains. By competitively binding BRD4 with chromatin at a concentration of (+)-JQ1 (500 nM), NMC cells' differentiation and growth are arrested. By reducing Ki67 staining, (+)-JQ1 (500 nM) inhibits the NMC 797 and Per403 cell lines' rapid proliferation. In NMC 797 cells, (+)-JQ1 (500 nM) significantly reduces the expression of both BRD4 target genes. In NMC 11060 cells, (+)-JQ1 inhibits cellular viability with an IC50 value of 4 nM. [1] In MM cell lines, (+)-JQ1 strongly inhibits MYC expression. KMS-34 and LR5 proliferation are both inhibited by (+)-JQ1 with IC50 values of 68 nM and 98 nM, respectively. (+)-JQ1 (500 nM)-treated MM.A significant reduction in the percentage of cells in the S-phase is caused by 1S cells, and cells arrested in G0/G1 are consequently more numerous. Using beta-galactosidase staining, (+)-JQ1 (500 nM) causes noticeable cellular senescence. The majority of the CD138+ patient-derived MM samples examined exhibit a significant reduction in cell viability following exposure to (+)-JQ1 (800 nM).[2] A GI50 of 98 nM for (+)-JQ1's ability to inhibit LP-1 cell growth. A greater proportion of LP-1 cells are in G0/G1 after treatment with (+)-JQ1 (625 nM). MYC, BRD4, and CDK9 expression in LP-1 cells is suppressed by (+)-JQ1 (500 nM).[3] In latently infected Jurkat T cells, (+)-JQ1 (1 μM) activates HIV transcription. Both Jurkat and HeLa cells are stimulated by (+)-JQ1 (50 μM) primarily Tat-dependent HIV transcription. In J-Lat A2 cells, (+)-JQ1 (5 μM) induces Brd4 dissociation, which allows Tat to attract SEC to the HIV promoter and trigger Pol II CTD phosphorylation and viral transcription. In Jurkat T cells, JQ1 partially separates P-TEFb from 7SK snRNP and enables Tat to increase CDK9 T-loop phosphorylation. [4]
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| ln Vivo |
In mice with NMC 797 xenografts, (+)-JQ1 (50 mg/kg) prevents tumor growth. In mice with NMC 797 xenografts, (+)-JQ1 (50 mg/kg) causes effacement of NUT nuclear speckles, which is consistent with competitive binding to nuclear chromatin. Strong (grade 31) keratin expression is induced in NMC 797 xenografts by (+)-JQ1 (50 mg/kg). In mice models of NMC xenografts, (+)-JQ1 (50 mg/kg) encourages differentiation, tumor regression, and increased survival. [1] When SCID-beige mice are orthotopically xenografted with MM.1S-luc+ cells via intravenous injection, (+)-JQ1 (50 mg/kg) significantly increases overall survival compared to vehicle-treated animals. [2] Mice carrying Raji xenografts experience a highly significant increase in survival when given (+)-JQ1 (50 mg/kg i.p.). [3]
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| Enzyme Assay |
(+)-JQ1 is a potent and highly specific BET (Bromodomain and extra terminal domain) bromodomain inhibitor, with IC50 of 77 nM and 33 nM for BRD4(1/2) in enzymatic assays.
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| Cell Assay |
Cells are seeded into white, 384-well microtiter plates at 500 cells per well in a total volume of 50 μL media. The DMEM containing 1% penicillin/streptomycin and 10% FBS is used to cultivate the 797, TT, and TE10 cells. Per403 cells are raised in DMEM containing 20% FBS and 1% penicillin/streptomycin. NMC 11060 cells from patients are expanded in RPMI containing 10% FBS and 1% penicillin/streptomycin. Robotic pin transfer is used to deliver (+)-JQ1 to microtiter assay plates. Cells are lysed and wells are examined for total ATP content using a commercial proliferation assay after 48 hours of incubation at 37°C. Replicate measurements are examined in relation to dose, and estimates of the IC50 are computed using logistic regression (GraphPad Prism).
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| Animal Protocol |
In vivo formulations used (reported):
1. Dissolved in 5% dextrose; 50 mg/kg; i.p. injection; Nature. 2010 Dec 23;468(7327):1067-73 2. Dissolved in 10% DMSO and 90% of a 10% 2-hydroxypropyl-β-cyclodextrin solution; Leukemia. 2017 Oct;31(10):2037-2047 3. Dissolved in 1% DMSO+5% Glucose+ddH2O; Cell. 2018 Sep 20;175(1):186-199.e19 4. Dissolved in 20% hydroxypropyl-β-cyclodextrin, 5% DMSO, 0.2% Tween-80 in saline; Mol Cancer Ther. 2016 Jun;15(6):1217-26 5. Dissolved in 1:1 propylene glycol:water; J Biol Chem. 2016 Nov 4;291(45):23756-23768 6. Dissolved in 5% DMSO in 10% 2-hydroxypropyl-β-cyclodextrin solution; Cancer Lett. 2017 Aug 28;402:100-109 |
| References | |
| Additional Infomation |
LSM-6333 is an organonitrogen heterocyclic compound, an organosulfur heterocyclic compound and a tert-butyl ester.
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| Molecular Formula |
C23H25CLN4O2S
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|---|---|---|
| Molecular Weight |
456.99
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| Exact Mass |
456.138
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| Elemental Analysis |
C, 60.45; H, 5.51; Cl, 7.76; N, 12.26; O, 7.00; S, 7.02
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| CAS # |
1268524-71-5
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| Related CAS # |
(+)-JQ-1;1268524-70-4;JQ-1 (carboxylic acid);202592-23-2
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| PubChem CID |
49871818
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| Appearance |
Light yellow to yellow solid
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
610.4±65.0 °C at 760 mmHg
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| Flash Point |
322.9±34.3 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.657
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| LogP |
4.49
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
706
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])C1C2C(C([H])([H])[H])=C(C([H])([H])[H])SC=2N2C(C([H])([H])[H])=NN=C2[C@@]([H])(C([H])([H])C(=O)OC(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N=1
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| InChi Key |
DNVXATUJJDPFDM-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C23H25ClN4O2S/c1-12-13(2)31-22-19(12)20(15-7-9-16(24)10-8-15)25-17(11-18(29)30-23(4,5)6)21-27-26-14(3)28(21)22/h7-10,17H,11H2,1-6H3/t17-/m1/s1
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| Chemical Name |
tert-butyl 2-[(9R)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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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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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
| 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. |
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 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. |
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 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. |
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 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. |
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 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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