EPZ015666 (Synonyms: GSK3235025)

Name: EPZ015666
Brand: MedChemExpress
SKU: HY-12727
Rating: 5.0 (16 reviews)

Cat. No.: HY-12727 Purity: 99.52%: FAQs
Data Sheet SDS COA Handling Instructions

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EPZ015666 (GSK3235025) is an orally available inhibitor of PRMT5 with an IC₅₀ of 22 nM.

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

EPZ015666 Chemical Structure

CAS No. : 1616391-65-1

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 121	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 121	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 52	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 110	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 165	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 495	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 715	In-stock	Estimated Time of Arrival: December 31
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500 mg		Get quote

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Customer Review

Based on 16 publication(s) in Google Scholar

16 Publications Citing Use of MCE EPZ015666

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•Related Screening Libraries:

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View All Histone Methyltransferase Isoform Specific Products:

View All Isoforms

EZH1 EZH2 DOT1L SMYD2 SMYD3 SUV39H2/KMT1B EHMT2/G9a/KMT1C EHMT1/GLP/KMT1D SETDB1/KMT2G SETD2/KMT3A NSD2/MMSET/WHSC1 SETD7/KMT7 SETD8/KMT5A PRMT1 PRMT3 PRMT4 PRMT5 PRMT6 PRMT7 PRMT8

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

EPZ015666 (GSK3235025) is an orally available inhibitor of PRMT5 with an IC₅₀ of 22 nM.

IC₅₀ & Target

PRMT5

Cellular Effect

Cell Line	Type	Value	Description	References
HCC38	IC₅₀	5 μM Compound: 66; EPZ015666, GSK3235025	Anticancer activity against human HCC38 cells assessed as cell growth inhibition by MTT assay Anticancer activity against human HCC38 cells assessed as cell growth inhibition by MTT assay	[PMID: 33650861]
KARPAS-422	IC₅₀	0.96 μM Compound: 8; EPZ015666	Antiproliferative activity against human KARPAS422 cells after 4 days by cell titer-glo luminescent cell viability assay Antiproliferative activity against human KARPAS422 cells after 4 days by cell titer-glo luminescent cell viability assay	[PMID: 30366617]
Maver1	IC₅₀	450 nM Compound: 1	Antiproliferative activity against human Maver1 cells measured after 12 days post culturing by guava via count reagent assay Antiproliferative activity against human Maver1 cells measured after 12 days post culturing by guava via count reagent assay	[PMID: 29870258]
MDA-MB-231	IC₅₀	60 μM Compound: 66; EPZ015666, GSK3235025	Anticancer activity against human MDA-MB-231 cells assessed as inhibition of cell proliferation by MTT assay Anticancer activity against human MDA-MB-231 cells assessed as inhibition of cell proliferation by MTT assay	[PMID: 33650861]
MDA-MB-468	IC₅₀	1 μM Compound: 66; EPZ015666, GSK3235025	Anticancer activity against human MDA-MB-468 cells assessed as cell growth inhibition by MTT assay Anticancer activity against human MDA-MB-468 cells assessed as cell growth inhibition by MTT assay	[PMID: 33650861]
MV4-11	GI₅₀	0.106 μM Compound: 1; EPZ015666	Antiproliferative activity against human MV4-11 cells supplemented with fresh medium containing compound every 4 days measured on day 12 by Celltiter-glo luminescent cell viability assay Antiproliferative activity against human MV4-11 cells supplemented with fresh medium containing compound every 4 days measured on day 12 by Celltiter-glo luminescent cell viability assay	[PMID: 30605830]
MV4-11	GI₅₀	0.212 μM Compound: 1; EPZ015666	Antiproliferative activity against human MV4-11 cells supplemented with fresh medium containing compound every 4 days measured on day 8 by Celltiter-glo luminescent cell viability assay Antiproliferative activity against human MV4-11 cells supplemented with fresh medium containing compound every 4 days measured on day 8 by Celltiter-glo luminescent cell viability assay	[PMID: 30605830]
MV4-11	IC₅₀	1.8 μM Compound: 8; EPZ015666	Antiproliferative activity against human MV4-11 cells after 4 days by cell titer-glo luminescent cell viability assay Antiproliferative activity against human MV4-11 cells after 4 days by cell titer-glo luminescent cell viability assay	[PMID: 30366617]
Pfeiffer	IC₅₀	1.1 μM Compound: 8; EPZ015666	Antiproliferative activity against human Pfeiffer cells after 4 days by cell titer-glo luminescent cell viability assay Antiproliferative activity against human Pfeiffer cells after 4 days by cell titer-glo luminescent cell viability assay	[PMID: 30366617]
SUD4	IC₅₀	2.6 μM Compound: 8; EPZ015666	Antiproliferative activity against human SU-DHL4 cells after 4 days by cell titer-glo luminescent cell viability assay Antiproliferative activity against human SU-DHL4 cells after 4 days by cell titer-glo luminescent cell viability assay	[PMID: 30366617]
Z-138	IC₅₀	351 nM Compound: EPZ015666; GSK3235025	Antiproliferative activity against human Z138 cells incubated for 5 days by cell titer-glo assay Antiproliferative activity against human Z138 cells incubated for 5 days by cell titer-glo assay	[PMID: 26985292]
Z-138	IC₅₀	96 nM Compound: 1	Antiproliferative activity against human Z138 cells measured after 12 days post culturing by guava via count reagent assay Antiproliferative activity against human Z138 cells measured after 12 days post culturing by guava via count reagent assay	[PMID: 29870258]

In Vitro

Treatment of MCL cell lines with EPZ015666 (GSK3235025) leads to inhibition of SmD3 methylation and cell death, with IC₅₀ values in the nanomolar range^[1]. EPZ015666 (GSK3235025), a potent peptide-competitive and SAM-cooperative inhibitor with >10,000-fold specificity against PRMT5 relative to other methyltransferases^[2].

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

In Vivo

EPZ015666 (GSK3235025) is orally bioavailable and amenable to in vivo studies. We performed 21-d efficacy studies in severe combined immunodeficiency (SCID) mice bearing subcutaneous Z-138 and Maver-1 xenografts, with twice-daily (BID) oral dosing on four dose groups: 25, 50, 100 and 200 mg per kilogram of body weight (mg/kg). After 21 d of continuous dosing, animals are euthanized, and blood and tissues are analyzed to determine the relationship between methyl-mark pharmacodynamics and tumor-growth inhibition (TGI). EPZ015666 (GSK3235025) showed dose-dependent exposure and TGI after 21 d in both MCL models. Tumors in all EPZ015666 (GSK3235025) dose groups measured on day 21 showed statistically significant differences in weight, volume and tumor growth compared to vehicle-treated tumors. Dosing at 200 mg/kg BID induced tumor stasis in Z-138 cells, with >93% TGI after 21 d, whereas Maver-1 cells showed >70% TGI. Additionally, a third MCL xenograft is tested using the Granta-519 cell line, a fast-growing model that reached endpoint on day 18 and showed dose-dependent efficacy with 45% TGI in the 200 mg/kg group. EPZ015666 (GSK3235025) is well tolerated in all three models, with minimal bodyweight loss in the 200 mg/kg dose group and no other clinical observations^[1].

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

Molecular Weight

383.44

Formula

C₂₀H₂₅N₅O₃

CAS No.

1616391-65-1

Appearance

Solid

Color

White to off-white

SMILES

O=C(NC[C@H](O)CN1CCC(C=CC=C2)=C2C1)C3=CC(NC4COC4)=NC=N3

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (260.80 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	2.6080 mL	13.0399 mL	26.0797 mL
5 mM	0.5216 mL	2.6080 mL	5.2159 mL
10 mM	0.2608 mL	1.3040 mL	2.6080 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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: ≥ 2.5 mg/mL (6.52 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: ≥ 2.5 mg/mL (6.52 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: ≥ 2.5 mg/mL (6.52 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 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 (25.0 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: 99.83%

Select Batch:

Data Sheet (277 KB) SDS (394 KB)

COA (245 KB) HNMR (180 KB) LCMS (305 KB)

Handling Instructions (2659 KB)

References

[1]. Chan-Penebre E, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol. 2015 Jun;11(6):432-7. [Content Brief]

[2]. Kryukov GV, et al. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science. 2016 Mar 11;351(6278):1214-8. [Content Brief]

Cell Assay ^[1]	Cultured cells in linear/log-phase growth are split to a seeding density of 2×10⁵ cells/mL in 2-20 mL of media, depending on the yield required at the end of the growth period. Compound is diluted in DMSO and added to each culture vessel with a final DMSO concentration of 0.2%. Cells are allowed to grow for 96 h undisturbed. At the conclusion of each treatment period, cells are harvested by centrifugation (5 min, 1,200 rpm), and cell pellets are rinsed once with PBS before being frozen on dry ice pending further processing. Long-term proliferation assays are performed on all MCL lines, with slight adjustments to initial seeding densities, depending on growth characteristics for each cell line. All assays are carried out for 12 d^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Mice^[1] Male CD-1 mice (25-40 g; n=6, with 3 per time point) are treated with a single dose of EPZ015666 (GSK3235025) at 2 mg/kg by intravenous tail-vein injection and 10 mg/kg by oral gavage administration, with both doses formulated in 20% N-N-dimethylacetamide in water. Animals are fasted overnight and weighed before dose administration on the day of dosing. Approximately 30 μL of blood are taken from animals by submandibular or retro-orbital bleeding at pre-specified time intervals (seven time points). For the last time point (24 h), samples are collected via cardiac puncture while the animals are under anesthesia (70% CO₂:30% O₂). Blood samples are transferred into K₂-EDTA tubes and placed on wet ice before centrifugation at 4°C (3,000g, 15 min) to obtain plasma within 30 min after sample collection. Plasma samples are stored at −70±10°C before protein precipitation and LC-MS/MS analysis. We constructed standard calibration curves by analyzing a series of control plasma aliquots containing 100 ng/mL labetalol as an internal standard and 1-3,000 ng/mL EPZ015666 (GSK3235025). Four levels of quality control are also included in the analysis (3-2,400 ng/mL EPZ015666 (GSK3235025)). Data are analyzed using Phoenix WinNonlin 6.2.1. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Chan-Penebre E, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol. 2015 Jun;11(6):432-7. [Content Brief] [2]. Kryukov GV, et al. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science. 2016 Mar 11;351(6278):1214-8. [Content Brief]

Complete Stock Solution Preparation Table

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

DMSO	1 mM	2.6080 mL	13.0398 mL	26.0797 mL	65.1992 mL
	5 mM	0.5216 mL	2.6080 mL	5.2159 mL	13.0398 mL
	10 mM	0.2608 mL	1.3040 mL	2.6080 mL	6.5199 mL
	15 mM	0.1739 mL	0.8693 mL	1.7386 mL	4.3466 mL
	20 mM	0.1304 mL	0.6520 mL	1.3040 mL	3.2600 mL
	25 mM	0.1043 mL	0.5216 mL	1.0432 mL	2.6080 mL
	30 mM	0.0869 mL	0.4347 mL	0.8693 mL	2.1733 mL
	40 mM	0.0652 mL	0.3260 mL	0.6520 mL	1.6300 mL
	50 mM	0.0522 mL	0.2608 mL	0.5216 mL	1.3040 mL
	60 mM	0.0435 mL	0.2173 mL	0.4347 mL	1.0867 mL
	80 mM	0.0326 mL	0.1630 mL	0.3260 mL	0.8150 mL
	100 mM	0.0261 mL	0.1304 mL	0.2608 mL	0.6520 mL

EPZ015666 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:

EPZ0156661616391-65-1GSK3235025EPZ 015666EPZ-015666GSK 3235025GSK-3235025Histone MethyltransferaseInhibitorinhibitorinhibit

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EPZ015666 (Synonyms: GSK3235025)

Customer Review

EPZ015666 Related Antibodies

16 Publications Citing Use of MCE EPZ015666

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All Histone Methyltransferase Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

EPZ015666 Related Antibodies

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Complete Stock Solution Preparation Table

EPZ015666 Related Classifications

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