XL888 | 99.86%(HPLC) | In Stock | HSP (HSP90) inhibitor

XL888 is an ATP-competitive inhibitor of HSP90 with IC50 of 24 nM. Phase 1.

XL888 Chemical Structure

CAS: 1149705-71-4

Selleck's XL888 has been cited by 5 Publications

1 Customer Review

Purity & Quality Control

Batch: S712201 DMSO] 100 mg/mL] false] Water] Insoluble] false] Ethanol] Insoluble] false Purity: 99.86%

99.86

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Signaling Pathway

HSP (HSP90) Signaling Pathway

Choose Selective HSP (HSP90) Inhibitors

Biological Activity

Description

XL888 is an ATP-competitive inhibitor of HSP90 with IC50 of 24 nM. Phase 1.

Targets

HSP90 ^[1]
(Cell-free assay)

24 nM

In vitro
In vitro	XL888 induces HER2 degradation in NCI-N87 cells with IC50 of 56 nM. XL888 inhibits the proliferation of HER2 over-expressed NCI-N87, HER2 over-expressed BT-474, HER2 over-expressed MDA-MB-453, MET mutated MKN45, B-Raf mutated Colo-205, B-Raf mutated SK-MEL-28, EGFR mutated HN5, EGFR mutated NCI-H1975, PI3K mutated MCF7, and K-Ras mutated A549 with IC50 of 21.8, 0.1, 16.0, 45.5, 11.6, 0.3, 5.5, 0.7, 4.1 and 4.3 nM. ^[1] XL888 leads to dose-dependent decreases in the growth of vemurafenib-naive and vemurafenib-resistant melanoma cell lines and melanoma cell lines with intrinsic resistance with IC50 of all around 0.1 μM. The growth inhibitory effects of XL888 are associated with induction of either a G₁-phase cell-cycle arrest (WM164, M229, M229R, M249, M249R, 1205Lu, and WM39 cell lines) or a G₂-M phase cell-cycle arrest (WM164R, 1205LuR, and RPMI 7951 cell lines). XL888 (300 nmol) induces high levels ( > 66%) of apoptosis, and loss of mitochondrial membrane potential (TMRM) in these cell lines. The cytotoxic effects of XL888 are durable with no signs of colony formation observed in any of the cell lines even cultured up to 4 weeks. XL888 treatment (300 nM, 48 hours) leads to the degradation of IGF1R, PDGFRβ, ARAF, CRAF, and cyclin D1 and the inhibition of AKT, ERK, and S6 signaling in all of the cell lines with acquired BRAF inhibitor resistance. treatment of cell lines that are naive, intrinsically resistant, and with acquired vemurafenib resistance. Treatment with XL888 (300 nM) leads to robust time-dependent increases in the expression of HSP70 isoform 1. XL888 (48 hours, 300 nM) treatment increases the expression of BIM-EL, BIM-L, and BIM-S expression in the M229R, 1205LuR, RPMI7951, and WM39 cell lines, induces expression of BIM-L and BIM-S in the WM164R cell line, and BIM-EL in the M249R cell line. ^[2]
Cell Research	Cell lines	1205Lu melanoma cells lines
	Concentrations	~10 μM
	Incubation Time	3 days
	Method	Cells are plated at a density of 2?0⁵ per mL and left to grow overnight before being treated with increasing concentrations of XL888. After incubation with XL888 for 3 days, Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays are performed.

In Vivo
In vivo	XL888 (100 mg/kg) significantly induces the regression of, or growth inhibition (50%) of established M229R and 1205LuR xenografts in SCID mice. 15 days of XL888 treatment showes a robust (8.6-fold) increase in intratumoral HSP70 expression compared with controls. XL888 treatment is noted to be proapoptotic in vivo and leads to increased TUNEL staining in M229R xenografts associated with increased expression of BIM and decreased expression of Mcl-1. ^[2]
Animal Research	Animal Models	Melanoma carcinoma xenografts 1205Lu
	Dosages	100 mg/kg
	Administration	3 times per week by oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT03095781	Completed	Colorectal Adenocarcinoma\|Metastatic Pancreatic Adenocarcinoma\|Recurrent Colorectal Carcinoma\|Recurrent Pancreatic Carcinoma\|Stage III Colorectal Cancer\|Stage III Pancreatic Cancer\|Stage IIIA Colorectal Cancer\|Stage IIIB Colorectal Cancer\|Stage IV Colorectal Cancer\|Stage IV Pancreatic Cancer\|Stage IVA Colorectal Cancer\|Stage IVA Pancreatic Cancer\|Stage IVB Colorectal Cancer\|Stage IVB Pancreatic Cancer\|Unresectable Pancreatic Carcinoma	Emory University\|Merck Sharp & Dohme LLC\|Exelixis\|National Institutes of Health (NIH)\|National Cancer Institute (NCI)	July 7 2017	Phase 1
NCT00796484	Terminated	Cancer	Exelixis	November 2008	Phase 1

References
[1] Bussenius J, et al. Bioorg Med Chem Lett, 2012, 22(17), 5396-5404. [2] Paraiso KH, et al. Clin Cancer Res, 2012, 18(9), 2502-2514.

References

Chemical Information & Solubility

Molecular Weight	503.64	Formula	C₂₉H₃₇N₅O₃
CAS No.	1149705-71-4	SDF	Download XL888 SDF
Smiles	CCC(C)NC1=C(C=C(C(=C1)C(=O)NC2CC3CCC(C2)N3C4=NC=C(C=C4)C(=O)C5CC5)C)C(=O)N
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (198.55 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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