(+)-JQ1 carboxylic acid is the free carboxylic acid (COOH) form of (+)-JQ1 (tert-Butyl ester form-COOtBu). (+)-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. (−)-JQ1 shows no significant interaction with any bromodomain. Besides, (−)-JQ1 enantiomer is comparatively inactive in nuclear protein in testis (NUT) midline carcinoma (NMC). (+)-JQ1 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.

Physicochemical Properties

Molecular Formula	C19H17CLN4O2S
Molecular Weight	400.88
Exact Mass	400.076
Elemental Analysis	C, 56.93; H, 4.27; Cl, 8.84; N, 13.98; O, 7.98; S, 8.00
CAS #	202592-23-2
Related CAS #	(+)-JQ-1;1268524-70-4;(R)-(-)-JQ1 Enantiomer; 1268524-71-5; 202592-23-2 (free); 1426257-60-4 (HCl); 2069219-37-8 (TFA); 2230314-61-9 (xTFA);
PubChem CID	66828107
Appearance	Typically exists as Off-white to yellow solids
Density	1.5±0.1 g/cm3
Boiling Point	661.6±65.0 °C at 760 mmHg
Flash Point	353.9±34.3 °C
Vapour Pressure	0.0±2.1 mmHg at 25°C
Index of Refraction	1.737
LogP	2.79
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Heavy Atom Count	27
Complexity	613
Defined Atom Stereocenter Count	1
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=C2C([H])(C([H])([H])C(=O)O[H])N=1
InChi Key	LJOSBOOJFIRCSO-AWEZNQCLSA-N
InChi Code	InChI=1S/C19H17ClN4O2S/c1-9-10(2)27-19-16(9)17(12-4-6-13(20)7-5-12)21-14(8-15(25)26)18-23-22-11(3)24(18)19/h4-7,14H,8H2,1-3H3,(H,25,26)/t14-/m0/s1
Chemical Name	2-[(9S)-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]acetic acid
Synonyms	(+)-JQ-1 carboxylic acid;(+)-JQ 1 carboxylic acid;(+)-JQ1 carboxylic acid; 202592-23-2; JQ-1 carboxylic acid; JQ-1 (carboxylic acid); (+)-JQ1 carboxylic acid; JQ1 Carboxylic Acid; 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-, (6S)-; (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetic acid; 2-[(9S)-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]acetic acid;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	BET/bromodomain and extra terminal domain
ln Vitro	On the surface of B16F10 cells, JQ-1 carboxylic acid reduces the expression of PD-L1 [1].
ln Vivo	(+)-JQ1 (50 mg/kg) inhibits tumors growth in mice with NMC 797 xenografts. (+)-JQ1 (50 mg/kg) results in effacement of NUT nuclear speckles in mice with NMC 797 xenografts, consistent with competitive binding to nuclear chromatin. (+)-JQ1 (50 mg/kg) induces strong (grade 31) keratin expression in NMC 797 xenografts. (+)-JQ1 (50 mg/kg) promotes differentiation, tumor regression and prolonged survival in mice models of NMC xenografts. (+)-JQ1 (50 mg/kg) results in a significant prolongation in overall survival of SCID-beige mice orthotopically xenografted after intravenous injection with MM.1S-luc+ cells compared to vehicle-treated animals. (+)-JQ1 (50 mg/kg i.p.) leads to a highly significant increase in survival of mice bearing Raji xenografts.
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	[1]. Design, Synthesis, and Evaluation of Trivalent PROTACs Having a Functionalization Site with Controlled Orientation. Bioconjug Chem. 2022 Jan 19;33(1):142-151. [2]. Dual drugs decorated bacteria irradiate deep hypoxic tumor and arouse strong immune responses. Biomaterials. 2022 Jul;286:121582.
Additional Infomation	Trivalent PROTACs having a functionalization site with controlled orientation were designed, synthesized, and evaluated. Based on the X-ray structure of BRD protein degrader MZ1 (1) in complex with human VHL and BRD4BD2, we expected that the 1,2-disubstituted ethyl group near the JQ-1 moiety in MZ1 (1) could be replaced by a planar benzene tether as a platform for further functionalization. To test this hypothesis, we first designed six divalent MZ1 derivatives, 2a-c and 3a-c, by combining three variations of substitution patterns on the benzene ring (1,2-, 1,3-, and 1,4-substitution) and two variations in the number of ethylene glycol units (2 or 1). We then tested the synthesized compounds for the BRD4 degradation activity of each. As expected, we found that 1,2D-EG2-MZ1 (2a), an MZ1 derivative with 1,2-disubstituted benzene possessing two ethylene glycol units, had an activity profile similar to that of MZ1 (1). Based on the structure of 2a, we then synthesized and evaluated four isomeric trivalent MZ1 derivatives, 15a-15d, having a tert-butyl ester unit on the benzene ring as a handle for further functionalization. Among the four isomers, 1,2,5T-EG2-MZ1 (15c) retained a level of BRD4 depletion activity similar to that of 2a without inducing a measurable Hook effect, and its BRD4 depletion kinetics was the same as that of MZ1 (1). Other isomers were also shown to retain BRD4 depletion activity. Thus, the trivalent PROTACs we synthesized here may serve as efficient platforms for further applications.[1] Intratumoral environment as a hypoxic, non-inflamed "cold" state is difficult for many agents to accumulate and activate the immune system. Intrinsically, facultative anaerobic Salmonella VNP20009 target the tumor hypoxic areas, invade into tumor cells and exhibit an immune effect. Here we engineer the bacteria by decorating their surface with newly synthesized heptamethine cyanine dyes NHS-N782 and JQ-1 derivatives to obtain the biohybrid agent N-V-J, leading to the deep tumor targeted photothermal therapy and magnified immunotherapy. Due to the mitochondrial targeting capacity of NHS-N782, N-V-J becomes susceptive to the temperature rise when reaching tumors. This synergistic strategy promotes the systemic immunity by creating an inflamed "hot" tumor state from three different dimensions, which include the inherent immunogenicity of bacteria, the near-infrared laser triggered tumor antigens and the downregulation of PD-L1 expression. All these approaches result in effective and long-lasting T cell immune responses to prevent local and distant tumors for extended time. Leveraging the attenuated bacteria to transport dual drugs to the tumor tissues for self-synthetic vaccines provides a novel paradigm to enhance the bacteria-mediated cancer immunotherapy.[2]

Solubility Data

Solubility (In Vitro)

DMSO: >120 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.24 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.24 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. Solubility in Formulation 3: ≥ 1.39 mg/mL (3.47 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 13.9 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 4: ≥ 1.39 mg/mL (3.47 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 13.9 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. Solubility in Formulation 5: ≥ 1.39 mg/mL (3.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 13.9 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4945 mL	12.4726 mL	24.9451 mL
	5 mM	0.4989 mL	2.4945 mL	4.9890 mL
	10 mM	0.2495 mL	1.2473 mL	2.4945 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.