XL888

Name: XL888
Brand: MedChemExpress
SKU: HY-13313
Rating: 5.0 (3 reviews)

Cat. No.: HY-13313 Purity: 99.39%: FAQs
Data Sheet SDS COA Handling Instructions

Molarity Calculator

XL888 is a heat shock protein-90 (HSP90) inhibitor, with an IC₅₀ of 24 nM.

For research use only. We do not sell to patients.

XL888 Chemical Structure

CAS No. : 1149705-71-4

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 183	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 183	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 55	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 165	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 264	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 495	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 902	In-stock	Estimated Time of Arrival: December 31
100 mg		Get quote
200 mg		Get quote

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Customer Review

Based on 3 publication(s) in Google Scholar

3 Publications Citing Use of MCE XL888

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View All Isoforms

HSP40 HSP70 HSP90 HSP105 HSF1 HSP HSPA5

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

XL888 is a heat shock protein-90 (HSP90) inhibitor, with an IC₅₀ of 24 nM.

IC₅₀ & Target^[3]

HSP90

24 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	4.3 nM Compound: 12i	Antiproliferative activity against human A549 cells overexpressing Kras after 48 hrs by BrdU labeling assay Antiproliferative activity against human A549 cells overexpressing Kras after 48 hrs by BrdU labeling assay	[PMID: 22877636]
BT-474	IC₅₀	0.1 nM Compound: 12i	Antiproliferative activity against human BT474 cells overexpressing Her2 after 48 hrs by BrdU labeling assay Antiproliferative activity against human BT474 cells overexpressing Her2 after 48 hrs by BrdU labeling assay	[PMID: 22877636]
COLO 205	IC₅₀	11.6 nM Compound: 12i	Antiproliferative activity against human COLO205 cells overexpressing Braf after 48 hrs by BrdU labeling assay Antiproliferative activity against human COLO205 cells overexpressing Braf after 48 hrs by BrdU labeling assay	[PMID: 22877636]
HN5	IC₅₀	5.5 nM Compound: 12i	Antiproliferative activity against human HN5 cells overexpressing EGFR after 48 hrs by BrdU labeling assay Antiproliferative activity against human HN5 cells overexpressing EGFR after 48 hrs by BrdU labeling assay	[PMID: 22877636]
MCF7	IC₅₀	4.1 nM Compound: 12i	Antiproliferative activity against human MCF7 cells overexpressing PI3K after 48 hrs by BrdU labeling assay Antiproliferative activity against human MCF7 cells overexpressing PI3K after 48 hrs by BrdU labeling assay	[PMID: 22877636]
MDA-MB-453	IC₅₀	16 nM Compound: 12i	Antiproliferative activity against human MDA-MB-453 cells overexpressing Her2 after 48 hrs by BrdU labeling assay Antiproliferative activity against human MDA-MB-453 cells overexpressing Her2 after 48 hrs by BrdU labeling assay	[PMID: 22877636]
MKN-45	IC₅₀	45.5 nM Compound: 12i	Antiproliferative activity against human MKN45 cells overexpressing MET after 48 hrs by BrdU labeling assay Antiproliferative activity against human MKN45 cells overexpressing MET after 48 hrs by BrdU labeling assay	[PMID: 22877636]
NCI-H1975	IC₅₀	0.7 nM Compound: 12i	Antiproliferative activity against human NCI-H1975 cells overexpressing EGFR after 48 hrs by BrdU labeling assay Antiproliferative activity against human NCI-H1975 cells overexpressing EGFR after 48 hrs by BrdU labeling assay	[PMID: 22877636]
NCI-N87	IC₅₀	21.8 nM Compound: 12i	Antiproliferative activity against human NCI-N87 cells overexpressing Her2 after 48 hrs by BrdU labeling assay Antiproliferative activity against human NCI-N87 cells overexpressing Her2 after 48 hrs by BrdU labeling assay	[PMID: 22877636]
NCI-N87	IC₅₀	56 nM Compound: 12i	Inhibition of Hsp90 in human NCI-N87 cells assessed as Her2 degradation after 24 hrs by Western blot analysis Inhibition of Hsp90 in human NCI-N87 cells assessed as Her2 degradation after 24 hrs by Western blot analysis	[PMID: 22877636]
SK-MEL-28	IC₅₀	0.3 nM Compound: 12i	Antiproliferative activity against human SK-MEL-28 cells overexpressing Braf after 48 hrs by BrdU labeling assay Antiproliferative activity against human SK-MEL-28 cells overexpressing Braf after 48 hrs by BrdU labeling assay	[PMID: 22877636]

In Vitro

XL888 is a heat shock protein-90 (HSP90) inhibitor. Treatment with XL888 leads to dose dependent decreases in the growth of all the cell lines with no significant difference in IC₅₀ values observed between the naive and resistance pairs of cell lines (t=0.25, p=0.82). Treatment of all of the vemurafenib resistant cell lines with XL888 (300 nM) induces high levels (>66%) of apoptosis, caspase-3 cleavage and loss of mitochondrial membrane potential (TMRM) in every cell line tested. Treatment of cell lines that are naïve, intrinsically resistant and with acquired vemurafenib resistance with XL888 (300 nM) leads to robust time-dependent increases in the expression of HSP70 isoform 1 (HSP71)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Treatment of the established M245 tumors with XL888 (125 mg/kg 3× week) leads to a significant slowing of tumor growth (P=0.017) without any effect upon animal weights. Analysis of xenograft specimens by LC-MRM shows a marked increase in intratumoral HSP70 expression following XL888 treatment^[1]. It is noted that the XL888 is well tolerated by the mice, with no significant alterations in body weigh observed over the study period. LC-MRM mediated analysis of xenograft samples following 15-days of XL888 treatment shows a robust (8.6-fold) increase in intratumoral HSP70 expression compare to controls^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

503.64

Formula

C₂₉H₃₇N₅O₃

CAS No.

1149705-71-4

Appearance

Solid

Color

Off-white to light yellow

SMILES

CC1=CC(C(N)=O)=C(N[C@H](C)CC)C=C1C(N[C@]2([H])C[C@H](CC3)N(C4=NC=C(C(C5CC5)=O)C=C4)[C@H]3C2)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 50 mg/mL (99.28 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.9855 mL	9.9277 mL	19.8555 mL
5 mM	0.3971 mL	1.9855 mL	3.9711 mL
10 mM	0.1986 mL	0.9928 mL	1.9855 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1.25 mg/mL (2.48 mM); Clear solution

This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 1.25 mg/mL (2.48 mM); Clear solution

This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 1.25 mg/mL (2.48 mM); Clear solution

This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.39%

Select Batch:

Data Sheet (276 KB) SDS (393 KB)

COA (248 KB) HNMR (223 KB) LCMS (111 KB)

Handling Instructions (2659 KB)

References

[1]. Haarberg HE, et al. Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma. Mol Cancer Ther. 2013 Jun;12(6):901-12. [Content Brief]

[2]. Paraiso KH, et al. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012 May 1;18(9):2502-14. [Content Brief]

[3]. Bussenius J, et al. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5396-404. [Content Brief]

Cell Assay ^[1]	Cells are plated in 96-well plates at 2×10⁴ per well. Media with vehicle (DMSO) or XL888 (10, 30, 100 or 300 nM) is added the following day and replaced twice a week. After 4 weeks the plates are stained with crystal violet^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[2]	BALB SCID mice are subcutaneously injected with 2.5×10⁶ cells per mouse and grown to approximately 100 mm³ prior to dosing. Mice are treated with either XL888 100 mg/kg (n=5) or an equivalent volume of vehicle (10 mM HCl), 3× per week by oral gavage. Mouse weights and tumor volumes (L×W²/2) are measured 3× per week. Upon completion of the experiment, vehicle and drug treated tumor biopsies are processed for LC-MRM analysi^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Haarberg HE, et al. Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma. Mol Cancer Ther. 2013 Jun;12(6):901-12. [Content Brief] [2]. Paraiso KH, et al. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012 May 1;18(9):2502-14. [Content Brief] [3]. Bussenius J, et al. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5396-404. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.9855 mL	9.9277 mL	19.8555 mL	49.6386 mL
	5 mM	0.3971 mL	1.9855 mL	3.9711 mL	9.9277 mL
	10 mM	0.1986 mL	0.9928 mL	1.9855 mL	4.9639 mL
	15 mM	0.1324 mL	0.6618 mL	1.3237 mL	3.3092 mL
	20 mM	0.0993 mL	0.4964 mL	0.9928 mL	2.4819 mL
	25 mM	0.0794 mL	0.3971 mL	0.7942 mL	1.9855 mL
	30 mM	0.0662 mL	0.3309 mL	0.6618 mL	1.6546 mL
	40 mM	0.0496 mL	0.2482 mL	0.4964 mL	1.2410 mL
	50 mM	0.0397 mL	0.1986 mL	0.3971 mL	0.9928 mL
	60 mM	0.0331 mL	0.1655 mL	0.3309 mL	0.8273 mL
	80 mM	0.0248 mL	0.1241 mL	0.2482 mL	0.6205 mL

XL888 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

XL8881149705-71-4XL 888XL-888HSPHeat shock proteinsInhibitorinhibitorinhibit

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XL888

Customer Review

XL888 Related Antibodies

3 Publications Citing Use of MCE XL888

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•Related Screening Libraries:

•Related Small Molecules:

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View All HSP Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

XL888 Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

XL888 Related Classifications

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