XL888

• CAT Number: I010101
• CAS Number: 1149705-71-4
• Molecular Formula: C₂₉H₃₇N₅O₃
• Molecular Weight: 503.64
• Purity: ≥95%
• Target: HSP
• Solubility: Soluble in DMSO, not in water
• Storage: 3 years -20℃ powder
• IUPAC Name: 2-[[(2R)-butan-2-yl]amino]-4-N-[8-[5-(cyclopropanecarbonyl)pyridin-2-yl]-8-azabicyclo[3.2.1]octan-3-yl]-5-methylbenzene-1,4-dicarboxamide
• InChI: nChI=1S/C29H37N5O3/c1-4-17(3)32-25-14-23(16(2)11-24(25)28(30)36)29(37)33-20-12-21-8-9-22(13-20)34(21)26-10-7-19(15-31-26)27(35)18-5-6-18/h7,10-11,14-15,17-18,20-22,32H,4-6,8-9,12-13H2,1-3H3,(H2,30,36)(H,33,37)/t17-,20?,21?,22?/m1/s1
• InChIKey: LHGWWAFKVCIILM-LAQKFSSHSA-N
• SMILES: CCC(C)NC1=CC(=C(C=C1C(=O)N)C)C(=O)NC2CC3CCC(C2)N3C4=NC=C(C=C4)C(=O)C5CC5

XL888 (Cat.No:I010101) is an orally bioavailable, ATP-competitive, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor XL888 specifically binds to Hsp90, inhibiting its chaperone function and promoting the proteasomal degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival; inhibition of tumor cell proliferation may result. Hsp90, a chaperone complex protein upregulated in a variety of tumor cell types, regulates the folding and degradation of many oncogenic signaling proteins, including Her-2 and Met.

Reference

1:XL888 Limits Vemurafenib-Induced Proliferative Skin Events by Suppressing Paradoxical MAPK Activation. Phadke M, Gibney GT, Rich CJ, Fedorenko IV, Chen YA, Kudchadkar RR, Sondak VK, Weber J, Messina JL, Smalley KS.J Invest Dermatol. 2015 Oct;135(10):2542-4. doi: 10.1038/jid.2015.205. Epub 2015 Jun 3. No abstract available. PMID: 26039542 Free PMC Article2:Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma. Haarberg HE, Paraiso KH, Wood E, Rebecca VW, Sondak VK, Koomen JM, Smalley KS.Mol Cancer Ther. 2013 Jun;12(6):901-12. doi: 10.1158/1535-7163.MCT-12-1003. Epub 2013 Mar 28. PMID: 23538902 Free PMC Article3:Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. 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.Bioorg Med Chem Lett. 2012 Sep 1;22(17):5396-404. doi: 10.1016/j.bmcl.2012.07.052. Epub 2012 Jul 21. PMID: 22877636 4:The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. 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.Clin Cancer Res. 2012 May 1;18(9):2502-14. doi: 10.1158/1078-0432.CCR-11-2612. Epub 2012 Feb 20. PMID: 22351686 Free PMC Article5:High-content, high-throughput analysis of cell cycle perturbations induced by the HSP90 inhibitor XL888. Lyman SK, Crawley SC, Gong R, Adamkewicz JI, McGrath G, Chew JY, Choi J, Holst CR, Goon LH, Detmer SA, Vaclavikova J, Gerritsen ME, Blake RA.PLoS One. 2011 Mar 7;6(3):e17692. doi: 10.1371/journal.pone.0017692. Erratum in: PLoS One. 2011;6(3). doi: 10.1371/annotation/73d83e95-8f14-48ed-bb67-2310a33e4ecc. PMID: 21408192 Free PMC Article