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XL-888Hsp90 inhibitor

XL-888

Catalog No. A4388
Size Price Stock Qty
10mM (in 1mL DMSO) $320.00 In stock
5mg $160.00 In stock
10mg $250.00 In stock
25mg $440.00 In stock
50mg $750.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & MSDS

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Chemical structure

XL-888

Biological Activity

Description XL-888 is an orally bioavailable, ATP-competitive, small-molecule inhibitor of heat shock protein 90 (Hsp90) with IC50 value of 24 nM.
Targets Hsp90          
IC50 24 nM          

Protocol

Cell experiment [1]:

Cell lines

Vemurafenib-resistant melanoma cell lines

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months.

Reaction Conditions

300 nM; 72 or 144 hrs

Applications

In Vemurafenib-resistant melanoma cell lines, XL888 (300 nM) induced high levels (> 66%) of apoptosis and loss of mitochondrial membrane potential.

Animal experiment [1]:

Animal models

Mice bearing M229R xenografts

Dosage form

100 mg/kg; p.o.; 3 times per week, for 15 days

Applications

XL888 (100 mg/kg) significantly induced the regression of established M229R xenografts in SCID mice.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Paraiso KH, Haarberg HE, Wood E, Rebecca VW, Chen YA, Xiang Y, Ribas A, Lo RS, Weber JS, Sondak VK, John JK, Sarnaik AA, Koomen JM, Smalley KS. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012; 18(9):2502-2514.

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Chemical Properties

Cas No. 1149705-71-4 SDF Download SDF
Synonyms Xl 888, Xl888
Chemical Name 2-(butan-2-ylamino)-4-N-[(1R,5S)-8-[5-(cyclopropanecarbonyl)pyridin-2-yl]-8-azabicyclo[3.2.1]octan-3-yl]-5-methylbenzene-1,4-dicarboxamide
Canonical SMILES CCC(C)NC1=CC(=C(C=C1C(=O)N)C)C(=O)NC2CC3CCC(C2)N3C4=NC=C(C=C4)C(=O)C5CC5
Formula C29H37N5O3 M.Wt 503.64
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips No
Shipping Condition No

Background

XL-888 is a novel and orally-bioavailable inhibitor of heat shock protein 90 (HSP90) that selectively inhibits HSP90α and HSP90β with values of 50% inhibition concentration IC50 of 22 nM and 44 nM respectively. It also exerts considerably weaker inhibition against a range of other diverse kinases with IC50 more than 3600 nM for all. X-ray crystallographic analysis reveals that the XL-888 binds to HSP90 through the formation of H-bonding between the N-(R)-sec-butylanthranilamide moiety of XL-888 and ASP93 of HSP90. In recent studies, XL-888 has exhibits strong anti-proliferative activities in a panel of tumor cells with values of IC50 ranging from 0.1 nM to 45.5 nM.

Reference

Paraiso KH, Haarberg HE, Wood E, Rebecca VW, Chen YA, Xiang Y, Ribas A, Lo RS, Weber JS, Sondak VK, John JK, Sarnaik AA, Koomen JM, Smalley KS. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012; 18(9):2502-2514

Bussenius J, Blazey CM, Aay N, Anand NK, Arcalas A, Baik T, Bowles OJ, Buhr CA, Costanzo S, Curtis JK, DeFina SC, Dubenko L, Heuer TS, Huang P, Jaeger C, Joshi A, Kennedy AR, Kim AI, Lara K, Lee J, Li J, Lougheed JC, Ma S, Malek S, Manalo JC, Martini JF, McGrath G, Nicoll M, Nuss JM, Pack M, Peto CJ, Tsang TH, Wang L, Womble SW, Yakes M, Zhang W, Rice KD. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett. 2012; 22(17): 5396-5404.