VER155008

Cas：1134156-31-2

Product Information：

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

Chemical Formula: C25H23Cl2N7O4

Exact Mass: 555.1189

Molecular Weight: 556.4 

Elemental Analysis: C, 53.97; H, 4.17; Cl, 12.74; N, 17.62; O, 11.50

Synonym: 

VER-155008

VER 155008

VER155008

Chemical Name:

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

InChi Key:

ZXGGCBQORXDVTE-UMCMBGNQSA-N

InChi Code:  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

Smiles Code:

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

Technical Data：

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life:>3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.03.00

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. VER-155008 (0.05-5 μM) reverses Aβ-induced axonal degeneration in cultured neurons. 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.

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. 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.

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.

4. Dong Q, Men R, Dan X, Chen Y, Li H, Chen G, Zee B, Wang MHT, He ML. Hsc70 regulates the IRES activity and serves as an antiviral target of enterovirus A71 infection. Antiviral Res. 2018 Feb;150:39-46. doi: 10.1016/j.antiviral.2017.11.020. Epub 2017 Nov 24. PubMed PMID: 29180285.

5. Sakai G, Tokuda H, Fujita K, Kainuma S, Kawabata T, Matsushima-Nishiwaki R, Kozawa O, Otsuka T. Heat Shock Protein 70 Negatively Regulates TGF-β-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts. Cell Physiol Biochem. 2017;44(3):1133-1145. doi: 10.1159/000485418. Epub 2017 Nov 27. PubMed PMID: 29179216.

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