HA15 |
Catalog No.GC19188
One-Click Copy Product Info
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HA15 is a molecule that specifically targets BiP/GRP78/HSPA5, binding to and inhibiting its ATPase activity, which leads to the dissociation of BiP from PERK, IRE1α, and ATF6, thereby triggering endoplasmic reticulum stress.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1609402-14-3
Sample solution is provided at 25 µL, 10mM.
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HA15 is a molecule that specifically targets BiP/GRP78/HSPA5, binding to and inhibiting its ATPase activity, which leads to the dissociation of BiP from PERK, IRE1α, and ATF6, thereby triggering endoplasmic reticulum stress[1][2][3]. HA15 has demonstrated anti-tumor effects in a variety of human cancers, including melanoma, breast, pancreas, and adrenocortical carcinoma[2].
HA15 (1-10μM, 24h) decreases melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO), with an IC50 of 1-2.5μM in A375 cells[1]. HA15 (10μM, 48h) induces typical dilated endoplasmic reticulum cisternae in A375 cells[1]. HA15 (1, 5 and 10μM; 48h) induces apoptosis in A375 cells by increasing the levels of the cleaved and activated form of caspase 9 and decreasing the levels of the zymogenic form of caspase 3[1].
HA15 (0.7mg/mouse, 5 days/week, 5 weeks, i.p.) treatment delayed tumor growth in malignant pleural mesothelioma (MPM) mouse model[2]. HA15 (0.5mg/kg twice weekly, 3 weeks, i.p.) in combination with BTZ, was more effective at inhibiting tumor growth than BTZ alone in a multiple myeloma mouse model[4].
References:
[1] Cerezo M, Lehraiki A, Millet A, et al. Compounds Triggering ER Stress Exert Anti-Melanoma Effects and Overcome BRAF Inhibitor Resistance. Cancer Cell. 2016 Jun 13;29(6):805-819.
[2] Xu D, Yang H, Yang Z, et al. Endoplasmic Reticulum Stress Signaling as a Therapeutic Target in Malignant Pleural Mesothelioma. Cancers (Basel). 2019 Oct 8;11(10):1502.
[3] Ruggiero C, Doghman-Bouguerra M, Ronco C, et al. The GRP78/BiP inhibitor HA15 synergizes with mitotane action against adrenocortical carcinoma cells through convergent activation of ER stress pathways. Mol Cell Endocrinol. 2018 Oct 15;474:57-64.
[4] Chen Y, Tao Y, Hu K, et al. GRP78 inhibitor HA15 increases the effect of Bortezomib on eradicating multiple myeloma cells through triggering endoplasmic reticulum stress. Heliyon. 2023 Sep 2;9(9):e19806.
| Cell experiment [1]: | |
Cell lines | Resistant melanoma cell lines A375 |
Preparation Method | A375 cells were treated with indicated concentrations (1-10μM) of HA15. After 24h, viable cells were counted using the trypan blue dye exclusion method. For trypan blue staining, 200μl of cells was aseptically transferred to a 1.5ml clear Eppendorf tube and incubated for 3min at room temperature with an equal volume of 0.4% trypan blue solution. Viable cells were counted and the results are expressed as the percentage of the value of control cells. |
Reaction Conditions | 1-10μM, 24h |
Applications | HA15 decreases melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO), with an IC50 of 1-2.5μM in A375 cells. |
| Animal experiment [2]: | |
Animal models | Malignant pleural mesothelioma (MPM) mouse model |
Preparation Method | Suspensions of tumor cells (in PBS) mixed with 1:1 with BD Matrigel Basement Membrane Matrix were subcutaneously inoculated in left and right flanks (BE261T cells: 1×106/injection). When tumors were palpable, mice were randomly assigned to treatment groups: (1) control; (2) Cisplatin (3.75mg/kg) plus Pemetrexed (83mg/kg) (i.p., once weekly) for five weeks; (3) HA15 (0.7mg/mouse, i.p., 5 days/week) for five weeks. Mice weight and tumor size were measured every three days. Tumor size was calculated as follows: (length × width × width)/2. At the endpoint, blood samples were collected through cardiac puncta and subjected to the determination of transaminase activities. |
Dosage form | 0.7mg/mouse, 5 days/week, 5 weeks, i.p. |
Applications | HA15 treatment delayed tumor growth in patient-derived xenograft models compared to the vehicle treatment. |
References: | |
| Cas No. | 1609402-14-3 | SDF | |
| Canonical SMILES | CC(NC1=NC(C2=CC=CC(NS(=O)(C3=C4C=CC=C(N(C)C)C4=CC=C3)=O)=C2)=CS1)=O | ||
| Formula | C23H22N4O3S2 | M.Wt | 466.58 |
| Solubility | DMSO : ≥ 50 mg/mL (107.16 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1433 mL | 10.7163 mL | 21.4326 mL |
| 5 mM | 428.7 μL | 2.1433 mL | 4.2865 mL |
| 10 mM | 214.3 μL | 1.0716 mL | 2.1433 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 5 reference(s) in Google Scholar.)