| Size | Price | Stock | Qty |
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| Targets |
The primary target of JG-231 is heat shock protein 70 (Hsp70). Hsp70 is a molecular chaperone involved in protein folding, protein quality control, and the cellular stress response. JG-231 acts as an allosteric inhibitor of Hsp70, disrupting the interaction between Hsp70 and BAG family proteins (including BAG1 and BAG3). By inhibiting the Hsp70-BAG interaction, JG-231 affects Hsp70-associated signaling pathways and induces apoptosis in cancer cells.
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| ln Vitro |
In vitro, JG-231 inhibits the binding of Hsp70 and BAG family proteins, including Hsp70-BAG1 with a Ki of 0.11 μM. JG-231 (0.31-5 μM; 4-10 days) inhibits tumor spheroid growth in a dose- and time-dependent manner in TT and MZ-CRC-1 cells in 3D culture. JG-231 (0-10 μM; 12-24 hours) disrupts the Hsp70-BAG3 interaction in MCF-7 cells, affects Hsp70-associated signaling pathways, and induces apoptosis. JG-231 reduces the levels of Akt, c-Raf, CDK4, IAP-1, and HuR, but does not change the levels of Hsp72 and Hsp90.
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| ln Vivo |
In vivo, JG-231 (4 mg/kg; intraperitoneal injection; three times a week; 4 weeks) has antitumor activity in a breast cancer xenograft mouse model. JG-231 inhibits tumor growth in MDA-MB-231 heterograft tumor models of triple negative breast cancer (TNBC). Treatment with JG-231 did not significantly change the weight of mice.
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| Enzyme Assay |
For Hsp70 inhibitors, standard cell-free assays include measuring the binding of Hsp70 to BAG family proteins using fluorescence polarization, AlphaScreen, or ELISA. The compound is incubated with recombinant Hsp70 and BAG proteins, and the inhibition of interaction is measured to determine Ki values. Surface plasmon resonance (SPR) can be used to measure binding affinity.
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| Cell Assay |
For Hsp70 inhibitors, standard cellular assays involve treatment of cancer cell lines with the test compound for 24-72 hours. Hsp70-BAG interaction is assessed by co-immunoprecipitation or proximity ligation assays. Apoptosis is assessed by Annexin V/PI staining, caspase activity assays, and DNA fragmentation. Cell viability is measured using MTT or CellTiter-Glo assays. Western blot analysis is used to assess signaling pathway modulation.
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| Animal Protocol |
For in vivo evaluation of Hsp70 inhibitors, standard animal models include tumor xenograft models using cancer cell lines sensitive to Hsp70 inhibition. JG-231 was evaluated in four-week-old female athymic mice bearing xenografted MDA-MB-231 cells. The compound was administered intraperitoneally at 4 mg/kg, three days a week for 4 weeks. Tumor growth and mouse body weight were monitored.
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| ADME/Pharmacokinetics |
In mice, JG-231 (5 mg/kg; i.p.) has a Cmax of 159 nM, Tmax of 2 h, t1/2 of 21.6 h, and AUC(0→5×∞) of 3401 nM·h. The compound has a molecular weight of 619.47 and formula C21H18BrCl2N3OS4. It is soluble in DMSO at 2 mg/mL. Storage conditions: 4°C, sealed storage, away from moisture and light; in solvent: -80°C for 6 months, -20°C for 1 month.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for JG-231. As a research compound targeting Hsp70, standard preclinical toxicology would be required for therapeutic development. JG-231 did not significantly change the weight of mice in the xenograft model, suggesting a tolerable safety profile at the tested dose. The compound is for research use only and not for therapeutic applications.
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| References |
Shao H, Li X, Moses MA, Gilbert LA, Kalyanaraman C, Young ZT, Chernova M, Journey SN, Weissman JS, Hann B, Jacobson MP, Neckers L, Gestwicki JE. Exploration of Benzothiazole Rhodacyanines as Allosteric Inhibitors of Protein-Protein Interactions with Heat Shock Protein 70 (Hsp70). J Med Chem. 2018 Jul 26;61(14):6163-6177. doi: 10.1021/acs.jmedchem.8b00583. Epub 2018 Jul 13. PubMed PMID: 29953808; PubMed Central PMCID: PMC6104643.
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| Additional Infomation |
JG-231 is an allosteric inhibitor targeting heat shock protein 70 (Hsp70). It is an analogue of JG-98 with anticancer effects. JG-231 inhibits the interaction of Hsp70-BAG3. The compound has antitumor activity in MDA-MB-231 heterograft tumor models of triple negative breast cancer (TNBC). No regulatory approval for therapeutic use has been identified.
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| Molecular Formula |
C22H18BRCL2N3OS4
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|---|---|
| Molecular Weight |
619.467816829681
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| Exact Mass |
616.889
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| CAS # |
1627126-59-3
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| Related CAS # |
1627240-10-1 (cation);1627126-59-3 (chloride);
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| PubChem CID |
134817195
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| Appearance |
Orange to reddish brown solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
814
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1=CC=C(C[N+]2C=CSC=2/C=C2/N(CC)C(C(=C3N(C)C4C=CC(=CC=4S3)Cl)S/2)=O)S1.[Cl-]
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| InChi Key |
LFKCNIBJPYBMOM-QPNALZDCSA-M
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| InChi Code |
InChI=1S/C22H18BrClN3OS4.ClH/c1-3-27-19(11-18-26(8-9-29-18)12-14-5-7-17(23)30-14)32-20(21(27)28)22-25(2)15-6-4-13(24)10-16(15)31-22/h4-11H,3,12H2,1-2H31H/q+1/p-1/b22-20+ SMILES
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| Chemical Name |
3-((5-Bromothiophen-2-yl)methyl)-2-((Z)-((E)-5-(6-chloro-3-methylbenzo[d]thiazol-2(3H)-ylidene)-3-ethyl-4-oxothiazolidin-2-ylidene)methyl)thiazol-3-ium chloride
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| Synonyms |
JG231 JG 231 JG-231
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO : ~2 mg/mL (~3.23 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6143 mL | 8.0714 mL | 16.1428 mL | |
| 5 mM | 0.3229 mL | 1.6143 mL | 3.2286 mL | |
| 10 mM | 0.1614 mL | 0.8071 mL | 1.6143 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.
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