Home Cytoskeletal Signaling HSP (HSP90) inhibitor XL888 For research use only.

XL888

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

XL888 Chemical Structure

XL888 Chemical Structure

CAS No. 1149705-71-4

Purity & Quality Control

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

XL888 Related Products

Signaling Pathway

HSP (HSP90) Signaling Pathways

HSP (HSP90) Signaling Pathway

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] 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. 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
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

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)

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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