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Purity: ≥98%
VER-155008 (VER 155008; VER155008) is an HSP70 (heat shock protein 70) inhibitor with anti-AD (alzheimer's disease) effects. It inhibits HSP70, HSC70 (Heat shock cognate 70), and GRP78 with IC50s of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays, respectively, and exhibits >100-fold selectivity for HSP70 over HSP90. VER-155008 significantly promoted axonal regrowth in amyloid β-treated neurons in vitro and improved object recognition, location, and episodic-like memory in 5XFAD mice. HSC70 may be used as a new therapeutic target for AD treatment.
| ln Vitro |
VER-155008 exhibits no activity against Hsp90, with an IC50 of >200 μM, however it is an inhibitor of Hsc70 and Hsp70, with IC50s of 0.5 μM, 2.6 μM, and 2.6 μM for Hsp70, Hsc70, and Grp7, respectively. BT474, MB-468, HCT116, and HT29 cells are among the human colon and breast tumor cell lines that VER-155008 suppresses in terms of proliferation, with GI50s of 10.4 μM, 14.4 μM, 5.3 μM, and 12.8 μM, respectively. HCT116 and BT474 cancer cells exhibit client protein degradation in response to VER-155008 (5–40 μM). Moreover, VER-155008 causes human tumor cell lines to undergo apoptosis[1]. In cultured neurons, VER-155008 (0.05-5 μM) restores Aβ-induced axonal degeneration[2]. VER-155008 (10 μM or 25 μM) inhibits Hsp70 and stops LNCaP95 cells from proliferating. Additionally, androgen receptor splice variation 7 (AR-V7) and full-length androgen receptor (AR-FL) protein expression are decreased by VER-155008[3].
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| ln Vivo |
In naive female BALB/c mice, VER-155008 (25 mg/kg, iv) shows plasma clearance. In HCT116 tumor-bearing nude BALB/c mice, VER-155008 (40 mg/kg, iv) likewise exhibits quick plasma clearance and lowers tumor levels[1]. In 5XFAD mice, VER-155008 (10 μmol/kg/day, ip) lessens axonal swelling linked to amyloid plaques and improves memory deficits. VER-155008 (89.9 μmol/kg/day, ip) also reduces amyloid plaques and the amyloid plaque-associated protein PHF-tau in 5XFAD mice[2].
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| References |
[1]. Massey AJ, et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol. 2010 Aug;66(3):535-45.
[2]. Yang X, et al. Heat Shock Cognate 70 Inhibitor, VER-155008, Reduces Memory Deficits and Axonal Degeneration in a Mouse Model of Alzheimer's Disease. Front Pharmacol. 2018 Jan 30;9:48. [3]. Kita K, et al. Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells. Cancer Sci. 2017 Sep;108(9):1820-1827 |
| Molecular Formula |
C25H23CL2N7O4
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| Molecular Weight |
556.40
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| CAS # |
1134156-31-2
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| Related CAS # |
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| SMILES |
O[C@@H]([C@H]([C@H](N1C(NCC2=CC=C(Cl)C(Cl)=C2)=NC3=C(N=CN=C31)N)O4)O)[C@H]4COCC5=CC=C(C#N)C=C5
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| Chemical Name |
5'-O-[(4-Cyanophenyl)methyl]-8-[[(3,4-dichlorophenyl)methyl]amino]-adenosine
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| Synonyms |
VER 155008; VER155008; VER-155008;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.49 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 25.0 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: ≥ 2.5 mg/mL (4.49 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.49 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1% CMC+0.5% Tween-80: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7973 mL | 8.9863 mL | 17.9727 mL | |
| 5 mM | 0.3595 mL | 1.7973 mL | 3.5945 mL | |
| 10 mM | 0.1797 mL | 0.8986 mL | 1.7973 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.
VER-155008 administration rescued memory deficits in 5XFAD mice.Front Pharmacol.2018 Jan 30;9:48. |
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VER-155008 penetrates into the brain after intraperitoneal administration in 5XFAD mice.Front Pharmacol.2018 Jan 30;9:48. |
VER-155008 administration reduced axonal swelling associated with amyloid plaques in 5XFAD mice.Front Pharmacol.2018 Jan 30;9:48. |
VER-155008 treatment reversed Aβ-induced axonal degeneration in cultured neurons.Front Pharmacol.2018 Jan 30;9:48. |
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VER-155008 administration reduced amyloid plaques in 5XFAD mice. Aβ1-40/42was visualized by immunostaining in the perirhinal cortex and hippocampal CA1.(A)Representative images of Aβ1-40/42-positive amyloid plaques in the perirhinal cortex are shown. The amyloid plaques are indicated with white arrowheads.Front Pharmacol.2018 Jan 30;9:48. |
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