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HSP27 inhibitor J2 is a novel and potent HSP27 inhibitor with anticancer activity. It can enhance the antiproliferative activity of 17-AAG and sensitize cisplatin-induced lung cancer cell growth inhibition.
| Targets |
- Heat Shock Protein 27 (HSP27): HSP27 inhibitor J2 is a functional inhibitor of HSP27, with an IC₅₀ of 2.3 μM for inhibiting HSP27 aggregation and a half-maximal inhibitory concentration (IC₅₀) of 3.1 μM for HSP27-mediated Akt phosphorylation [1]
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| ln Vitro |
In NCI-H460, the HSP27 inhibitor J2 (10 μM; 12 h) causes markedly aberrant HSP27 dimer formation [1]. HSP27 inhibitor J2 (10 μM; 24 h) raises myocardial 17-AAG-sensing shCTRL [1]. 】.
1. HSP27 aggregation inhibition: HSP27 inhibitor J2 dose-dependently inhibited the aggregation of recombinant HSP27 in vitro, with IC₅₀ = 2.3 μM. At 10 μM, it suppressed HSP27 aggregation by 85% compared to vehicle control [1] 2. Antiproliferative activity: The compound inhibited proliferation of human cancer cell lines with IC₅₀ values: A549 (lung adenocarcinoma, 4.2 μM), HCT116 (colorectal cancer, 3.8 μM), MCF-7 (breast cancer, 5.1 μM). No significant antiproliferative effect was observed in normal human lung fibroblasts (MRC-5, IC₅₀ > 30 μM) [1] 3. Apoptosis induction: HSP27 inhibitor J2 (5 μM, 24 hours) induced apoptosis in A549 cells, with apoptotic rate increasing from 4.3% (vehicle) to 38.6% (Annexin V/PI staining). Western blot showed upregulated cleaved caspase-3 (3.6-fold) and cleaved PARP (2.9-fold), and downregulated HSP27 (65% reduction) [1] 4. Inhibition of HSP27 downstream signaling: Treatment with HSP27 inhibitor J2 (3 μM, 12 hours) reduced HSP27-mediated Akt phosphorylation (p-Akt) by 72% in HCT116 cells, without affecting total Akt protein levels [1] 5. Anti-fibrotic activity in lung fibroblasts: HSP27 inhibitor J2 (2 μM) inhibited TGF-β1-induced proliferation of MRC-5 cells (inhibition rate = 42%) and reduced collagen I secretion (35% reduction vs. TGF-β1 alone) [2] |
| ln Vivo |
1. Anti-pulmonary fibrosis efficacy in mice: C57BL/6 mice were intratracheally injected with bleomycin (5 mg/kg) to induce pulmonary fibrosis. From day 7 post-modeling, mice were treated with HSP27 inhibitor J2 (10, 20 mg/kg, intraperitoneal injection, once daily) for 14 days. The 20 mg/kg group showed reduced lung collagen content (hydroxyproline level: 45.2 ± 4.8 μg/lung vs. 78.6 ± 6.2 μg/lung in vehicle), decreased alveolar wall thickening, and downregulated fibrosis markers (α-SMA, COL1A1, fibronectin) in lung tissues [2]
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| Enzyme Assay |
1. HSP27 aggregation inhibition assay: Recombinant HSP27 protein was dissolved in reaction buffer and incubated with serial concentrations of HSP27 inhibitor J2 (0.1–30 μM) at 37°C for 2 hours. The aggregation of HSP27 was monitored by measuring turbidity at 340 nm. The inhibition rate was calculated relative to vehicle control, and IC₅₀ was derived from dose-response curves [1]
2. HSP27-Akt interaction inhibition assay: Recombinant HSP27 and Akt proteins were co-incubated with HSP27 inhibitor J2 (0.5–20 μM) for 1 hour. The binding complex was captured by immunoprecipitation with anti-HSP27 antibody, and the amount of co-precipitated Akt was detected by Western blot. The IC₅₀ for inhibiting HSP27-Akt interaction was calculated [1] |
| Cell Assay |
1. Antiproliferative assay: Cancer cells (A549, HCT116, MCF-7) and normal fibroblasts (MRC-5) were seeded in 96-well plates and treated with HSP27 inhibitor J2 (0.1–100 μM) for 72 hours. Cell viability was measured using a cell proliferation assay kit, and IC₅₀ values were calculated [1]
2. Apoptosis assay: A549 cells were treated with HSP27 inhibitor J2 (5 μM) for 24 hours, stained with Annexin V-FITC and PI, and analyzed by flow cytometry to quantify apoptotic cells. Western blot was performed to detect cleaved caspase-3, cleaved PARP, and HSP27 protein levels [1] 3. TGF-β1-induced fibrosis model in fibroblasts: MRC-5 cells were serum-starved for 12 hours, pre-incubated with HSP27 inhibitor J2 (0.5–5 μM) for 1 hour, then treated with TGF-β1 (10 ng/mL) for 48 hours. Cell proliferation was measured by cell counting, and collagen I secretion was quantified using an ELISA kit [2] |
| Animal Protocol |
1. Bleomycin-induced pulmonary fibrosis model: Female C57BL/6 mice (6–8 weeks old) were anesthetized and intratracheally administered bleomycin (5 mg/kg) to induce pulmonary fibrosis. Mice in the sham group received normal saline. From day 7 after bleomycin administration, mice were randomly divided into vehicle (10% DMSO/40% PEG400/50% saline) and HSP27 inhibitor J2 groups (10, 20 mg/kg). The compound was administered via intraperitoneal injection once daily for 14 days. At the end of treatment, mice were sacrificed, and lung tissues were collected for hydroxyproline assay, histological staining (HE, Masson's trichrome), and Western blot analysis of fibrosis markers [2]
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| References | |
| Additional Infomation |
1. HSP27 inhibitor J2 is a chromone derivative designed as a functional inhibitor of HSP27, targeting HSP27 aggregation and its interaction with downstream signaling proteins [1]. 2. Its anticancer mechanism includes inhibiting the HSP27-mediated pro-survival signaling pathway (Akt pathway) and inducing caspase-dependent apoptosis in cancer cells [1]. 3. This compound exhibits antifibrotic activity by inhibiting TGF-β1-induced fibroblast proliferation and collagen secretion, supporting its potential for treating pulmonary fibrosis [2]. 4. HSP27 inhibitor J2 is selective for cancer cells and activated fibroblasts, with low toxicity to normal cells [1][2].
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| Molecular Formula |
C13H12O4S
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| Molecular Weight |
264.296982765198
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| Exact Mass |
264.045
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| CAS # |
2133499-85-9
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| PubChem CID |
135384973
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
18
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| Complexity |
381
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1CC1COC1C=C(C2C(C=C(C)OC=2C=1)=O)O
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| InChi Key |
VDCWAGBPDCXRDU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H12O4S/c1-7-2-10(14)13-11(15)3-8(4-12(13)17-7)16-5-9-6-18-9/h2-4,9,15H,5-6H2,1H3
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| Chemical Name |
5-hydroxy-2-methyl-7-(thiiran-2-ylmethoxy)chromen-4-one
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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 |
| 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 : ~20 mg/mL (~75.67 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (7.57 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 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 5 mg/mL (18.92 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; Need ultrasonic and warming and heat to 48°C. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7836 mL | 18.9179 mL | 37.8358 mL | |
| 5 mM | 0.7567 mL | 3.7836 mL | 7.5672 mL | |
| 10 mM | 0.3784 mL | 1.8918 mL | 3.7836 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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