VER155008

VER155008 is an inhibitor of HSP70. It acts by inhibiting reactivation of firefly luciferase.

Product information

CAS Number: 1134156-31-2

Molecular Weight: 556.40

Formula: C25H23Cl2N7O4

Synonym:

VER-155008

VER 155008

VER155008

Chemical Name: 5'-O-[(4-Cyanophenyl)methyl]-8-[[(3,4-dichlorophenyl)methyl]amino]-adenosine

Smiles: NC1=NC=NC2=C1N=C(NCC1=CC(Cl)=C(Cl)C=C1)N2[C@@H]1O[C@H](COCC2C=CC(=CC=2)C#N)[C@@H](O)[C@H]1O

InChiKey: ZXGGCBQORXDVTE-UMCMBGNQSA-N

InChi: InChI=1S/C25H23Cl2N7O4/c26-16-6-5-15(7-17(16)27)9-30-25-33-19-22(29)31-12-32-23(19)34(25)24-21(36)20(35)18(38-24)11-37-10-14-3-1-13(8-28)2-4-14/h1-7,12,18,20-21,24,35-36H,9-11H2,(H,30,33)(H2,29,31,32)/t18-,20-,21-,24-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

VER155008 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. VER155008 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. VER155008 (5-40 μM) induces client protein degradation in HCT116 and BT474 carcinoma cells. VER155008 also induces apoptosis in human tumor cell lines. VER155008 (0.05-5 μM) reverses Aβ-induced axonal degeneration in cultured neurons. VER155008 (10 μM or 25 μM) inhibits Hsp70 and suppresses the proliferation of LNCaP95 cells. VER155008 also reduces full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) protein expression.

In Vivo:

VER155008 (25 mg/kg, i.v.) exhibits plasma clearance in naive female BALB/c mice. VER155008 (40 mg/kg, i.v.) also shows rapid plasma clearance, and reduces the tumor levels in the HCT116 tumor bearing nude BALB/c mice. VER155008 (10 μmol/kg/day, i.p.) rescues memory deficits, and reduces axonal swelling associated with amyloid plaques in 5XFAD mice. VER155008 (89.9 μmol/kg/day, i.p.) penetrates into the brain after administration in 5XFAD mice. VER155008 also decreases amyloid plaques and PHF-tau associated with amyloid plaques in 5XFAD mice.

References:

1. Tian Y, Xu H, Farooq AA, Nie B, Chen X, Su S, Yuan R, Qiao G, Li C, Li X, Liu X, Lin X. Maslinic acid induces autophagy by down-regulating HSPA8 in pancreatic cancer cells. Phytother Res. 2018 Mar 8. doi: 10.1002/ptr.6064. [Epub ahead of print] PubMed PMID: 29516568.
2. Yang X, Tohda C. 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. doi: 10.3389/fphar.2018.00048. eCollection 2018. PubMed PMID: 29441022; PubMed Central PMCID: PMC5797615.
3. Morey TM, Winick-Ng W, Seah C, Rylett RJ. Chaperone-Mediated Regulation of Choline Acetyltransferase Protein Stability and Activity by HSC/HSP70, HSP90, and p97/VCP. Front Mol Neurosci. 2017 Dec 12;10:415. doi: 10.3389/fnmol.2017.00415. eCollection 2017. PubMed PMID: 29311808; PubMed Central PMCID: PMC5733026

Products are for research use only. Not for human use.