| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
HSPA5 0.59 μM (IC50)
GRP78-IN-3 selectively targets the 78 kDa glucose-regulated protein (GRP78), also known as HSPA5. GRP78 is a major endoplasmic reticulum (ER) chaperone protein involved in protein folding and the unfolded protein response (UPR). It is often overexpressed in cancer cells, promoting survival and resistance to chemotherapy. The compound competitively inhibits Hsp70 substrate binding, disrupting the chaperone function of GRP78. It exhibits selectivity for HspA5 over HspA9 and HspA2. |
|---|---|
| ln Vitro |
GRP78-IN-3 (compound 8) is a strong small-molecule competitive inhibitor of Hsp70 substrate binding. In a spheroid tumor model (U251 glioblastoma cells and H520 lung cancer cells), GRP78-IN-3 (0.1-100 μM) exhibits more potent inhibitory effects[1].
In vitro, GRP78-IN-3 demonstrates potent inhibitory activity against GRP78 (HSPA5) with an IC50 of 0.59 μM. It shows 7-fold selectivity for HspA5 over HspA9 (IC50 = 4.3 μM) and >20-fold selectivity over HspA2 (IC50 = 13.9 μM). In spheroid tumor models (U251 glioblastoma cells and H520 lung cancer cells), GRP78-IN-3 (0.1-100 μM) demonstrated enhanced inhibitory effects compared to monolayer cultures. These results suggest the compound's potential as an anti-cancer agent. |
| ln Vivo |
In vivo data for GRP78-IN-3 is limited in publicly available sources. As a GRP78 inhibitor with potent in vitro activity, the compound is expected to have potential applications in cancer models where GRP78 is overexpressed. By disrupting cancer cell survival mechanisms and sensitizing tumors to chemotherapy, GRP78-IN-3 could enhance the efficacy of existing treatments. However, specific published in vivo efficacy studies are not widely reported for this compound.
|
| Enzyme Assay |
The in vitro GRP78 inhibition assay for GRP78-IN-3 typically uses recombinant GRP78 (HSPA5) protein and a fluorescently labeled peptide substrate. The compound's competitive inhibition of Hsp70 substrate binding is measured by monitoring the displacement of the substrate peptide from the chaperone protein. IC50 values are calculated from dose-response curves. Selectivity profiling against HspA9 and HspA2 is performed using similar assay formats to confirm the compound's specificity.
|
| Cell Assay |
Cellular activity of GRP78-IN-3 is assessed in cancer cell lines such as U251 glioblastoma cells and H520 lung cancer cells. Cells are treated with varying concentrations of the compound (0.1-100 μM) in both monolayer and spheroid cultures. Cell viability and proliferation are measured using standard assays. The compound's effects on the unfolded protein response and ER stress pathways are evaluated by Western blotting for markers such as CHOP, BiP, and XBP-1. Spheroid models are used to assess efficacy in a more physiologically relevant 3D context.
|
| Animal Protocol |
In vivo studies for GRP78-IN-3 would typically involve xenograft mouse models of cancers with high GRP78 expression. The compound would be administered via intraperitoneal or oral routes at doses determined by pharmacokinetic studies. Efficacy would be assessed by measuring tumor growth inhibition, with pharmacodynamic markers such as GRP78 expression and UPR pathway activation evaluated in tumor tissues. However, specific published in vivo protocols for GRP78-IN-3 are not available in the current literature.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for GRP78-IN-3 is not extensively reported in publicly available sources. The compound has a molecular weight of 342.42 g/mol and is slightly soluble in DMSO. As a small molecule inhibitor of GRP78, it is expected to have moderate bioavailability. Detailed PK parameters such as half-life, clearance, and volume of distribution are not available in the current literature for this research compound.
|
| Toxicity/Toxicokinetics |
Toxicity data for GRP78-IN-3 is limited in publicly available sources. As with all research compounds, GRP78-IN-3 is intended for research use only and not for human therapeutic applications. The compound's selectivity for GRP78 over other Hsp70 family members suggests a favorable off-target profile, but comprehensive toxicology studies have not been reported. Standard in vitro cytotoxicity assays and in vivo tolerability studies would be required for a complete toxicity assessment.
|
| References | |
| Additional Infomation |
GRP78-IN-3 is a selective competitive inhibitor of GRP78 (HSPA5) with sub-micromolar potency (IC50 = 0.59 μM). It shows selectivity for HspA5 over HspA9 (7-fold) and HspA2 (>20-fold). By inhibiting GRP78, the compound disrupts cancer cell survival mechanisms and may sensitize tumors to chemotherapy. It has shown enhanced efficacy in spheroid tumor models. GRP78-IN-3 is a valuable tool for studying the role of GRP78 in cancer biology, the unfolded protein response, and therapeutic resistance.
|
| Exact Mass |
342.115
|
|---|---|
| CAS # |
2707510-30-1
|
| PubChem CID |
156853728
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
24
|
| Complexity |
474
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC(C)[C@@H](C(=O)NC1=NC=CS1)NC(=O)C2=CC3=CC=CC=C3N2
|
| InChi Key |
XOWYFNSUXHAORU-AWEZNQCLSA-N
|
| InChi Code |
InChI=1S/C17H18N4O2S/c1-10(2)14(16(23)21-17-18-7-8-24-17)20-15(22)13-9-11-5-3-4-6-12(11)19-13/h3-10,14,19H,1-2H3,(H,20,22)(H,18,21,23)/t14-/m0/s1
|
| Chemical Name |
N-[(2S)-3-methyl-1-oxo-1-(1,3-thiazol-2-ylamino)butan-2-yl]-1H-indole-2-carboxamide
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 5 mg/mL (14.60 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (1.46 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 5.0 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: ≥ 0.5 mg/mL (1.46 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 5.0 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.) |
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
