Name | 5'-O-[(4-Cyanophenyl)methyl]-8-[[(3,4-dichlorophenyl)methyl]amino]-adenosine |
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Synonyms |
5'-O-(4-Cyanobenzyl)-8-[(3,4-dichlorobenzyl)amino]adenosine
4-[[(2R,3S,4R,5R)-5-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile Adenosine, 5'-O-[(4-cyanophenyl)methyl]-8-[[(3,4-dichlorophenyl)methyl]amino]- VER-155008 |
Description | VER-155008 is an inhibitor of Hsp70, with IC50s of 0.5 μM, 2.6 μM, and 2.6 μM for Hsp70, Hsc70 and Grp7, respectively, and with a Kd of 0.3 μM for Hsp70. |
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Related Catalog | |
Target |
HSP70:0.5 μM (IC50) HSC70:2.6 μM (IC50) Grp78:2.6 μM (IC50) |
In Vitro | VER-155008 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, a with a Kd of 0.3 μM for Hsp70, but shows no activities against Hsp90, with an IC50 of >200 μM. VER-155008 inhibits the proliferation of a variety of human colon and breast tumor cell lines, such as BT474, MB-468, HCT116 and HT29 cells, with GI50s of 10.4 μM, 14.4 μM, 5.3 μM, and 12.8 μM, respectively. VER-155008 (5-40 μM) induces client protein degradation in HCT116 and BT474 carcinoma cells. VER-155008 also induces apoptosis in human tumor cell lines[1]. VER-155008 (0.05-5 μM) reverses Aβ-induced axonal degeneration in cultured neurons[2]. VER-155008 (10 μM or 25 μM) inhibits Hsp70 and suppresses the proliferation of LNCaP95 cells. VER-155008 also reduces full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) protein expression[3]. |
In Vivo | VER-155008 (25 mg/kg, i.v.) exhibits plasma clearance in naive female BALB/c mice. VER-155008 (40 mg/kg, i.v.) also shows rapid plasma clearance, and reduces the tumor levels in the HCT116 tumor bearing nude BALB/c mice[1]. VER-155008 (10 μmol/kg/day, i.p.) rescues memory deficits, and reduces axonal swelling associated with amyloid plaques in 5XFAD mice. VER-155008 (89.9 μmol/kg/day, i.p.) penetrates into the brain after administration in 5XFAD mice. VER-155008 also decreases amyloid plaques and PHF-tau associated with amyloid plaques in 5XFAD mice[2]. |
Cell Assay | Embryos are removed from a pregnant ddY mouse at 14 days of gestation. Cells are treated with or without 10 μM Aβ25-35 for 3 days, followed by the addition of 0.05, 0.5, or 5 μM VER-155008 or vehicle solution (0.1% DMSO) for 4 days. The Aβ25-35 is incubated at 37°C for 4 days prior to treatment to facilitate aggregation. The cells are fixed with 4% paraformaldehyde and immunostained at 4°C for 24 h with antibodies against the axonal marker, mouse phosphorylated neurofilament heavy subunit, and against the neuronal marker, rabbit microtubule-associated protein 2. Alexa Fluor 488-conjugated goat anti-mouse IgG (1:400) and Alexa Fluor 568-conjugated goat anti-rabbit IgG (1:400) are used as secondary antibodies. Fluorescence images (864.98 μm × 645.62 μm) are captured using a fluorescence microscopy system. The lengths of the pNF-H-positive axons are measured using MetaMorph version 7.8[2]. |
Animal Admin | Female BALB/c mice are dosed intravenously with 25 mg/kg VER-155008 into the lateral tail vein as a solution in 10% DMSO/5% Tween 80/85% saline (v/v/v). Animals are sacrificed at 5, 15 and 30 min, 1, 2, 4 and 6 h post dose[1]. |
References |
Density | 1.6±0.1 g/cm3 |
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Boiling Point | 856.3±75.0 °C at 760 mmHg |
Molecular Formula | C25H23Cl2N7O4 |
Molecular Weight | 556.401 |
Flash Point | 471.7±37.1 °C |
Exact Mass | 555.118835 |
PSA | 164.36000 |
LogP | 2.71 |
Vapour Pressure | 0.0±0.3 mmHg at 25°C |
Index of Refraction | 1.748 |
Storage condition | -20℃ |
RIDADR | NONH for all modes of transport |
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HS Code | 2934999090 |
~58% 1134156-31-2 |
Literature: Williamson, Douglas S.; Borgognoni, Jenifer; Clay, Alexandra; Daniels, Zoe; Dokurno, Pawel; Drysdale, Martin J.; Foloppe, Nicolas; Francis, Geraint L.; Graham, Christopher J.; Howes, Rob; Macias, Alba T.; Murray, James B.; Parsons, Rachel; Shaw, Terry; Surgenor, Allan E.; Terry, Lindsey; Wang, Yikang; Wood, Mike; Massey, Andrew J. Journal of Medicinal Chemistry, 2009 , vol. 52, # 6 p. 1510 - 1513 |
HS Code | 2934999090 |
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Summary | 2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |