XL888 | HSP inhibitor | CAS 1149705-71-4

Jump to

Quality Control

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

Cited in Nature Medicine for its top-tier quality
COA
NMR
SDS
Datasheet

99.86

Related Targets	Akt Wnt/beta-catenin PKC ROCK Microtubule Associated Integrin Bcr-Abl Actin FAK Kinesin
Other HSP Inhibitors	Tanespimycin (17-AAG) Elesclomol (STA-4783) Luminespib (NVP-AUY922) Ganetespib (STA-9090) Alvespimycin (17-DMAG) Hydrochloride VER-155008 Onalespib (AT13387) BIIB021 Zelavespib (PU-H71) HSP990 (NVP-HSP990)

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (198.55 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%PEG400 1 0.5%Tween80 2 5%propylene glycol Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (59.57mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	503.64	Formula	C₂₉H₃₇N₅O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1149705-71-4	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			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

Mechanism of Action

Targets/IC₅₀/Ki	HSP90 (Cell-free assay) 24 nM
In vitro	XL888 induces HER2 degradation in NCI-N87 cells with IC50 of 56 nM. This compound 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. The growth inhibitory effects of this compound 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). This chemical (300 nmol) induces high levels ( > 66%) of apoptosis, and loss of mitochondrial membrane potential (TMRM) in these cell lines. The cytotoxic effects of this compound are durable with no signs of colony formation observed in any of the cell lines even cultured up to 4 weeks. Treatment with this chemical (300 nM) leads to robust time-dependent increases in the expression of HSP70 isoform 1. This compound (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.
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 this compound treatment showes a robust (8.6-fold) increase in intratumoral HSP70 expression compared with controls. This compound 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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/22877636/ [2] https://pubmed.ncbi.nlm.nih.gov/22351686/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

XL888 HSP inhibitor

Chemical Structure

Molecular Weight: 503.64