CPI-169

Alias: CPI 169; CPI169; CPI-169;(R,Z)-1-(1-(1-(ethylsulfonyl)piperidin-4-yl)ethyl)-N-((2-hydroxy-4-methoxy-6-methylpyridin-3-yl)methyl)-2-methyl-1H-indole-3-carbimidic acid

Cat No.:V0389 Purity: ≥98%

COA Product Data Instructions for use SDS

CPI-169 (CPI169) is a novel, potent, and selective inhibitor of EZH2 (enhancer of zeste homolog 2) inhibitor with anticancer activity.

CPI-169 Chemical Structure CAS No.: 1450655-76-1
Product category: Histone Methyltransferase

This product is for research use only, not for human use. We do not sell to patients.

Size	Price	Stock	Qty
1mg
5mg
10mg
25mg
50mg
100mg
Other Sizes

ADD TO CART CHECKOUT BULK INQUIRY

1-708-310-1919 sales@invivochem.com

Official Supplier of:

Business Relationship with 5000+ Clients Globally
Major Universities, Research Institutions, Biotech & Pharma
Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

CPI-169 (CPI169) is a novel, potent, and selective inhibitor of EZH2 (enhancer of zeste homolog 2) inhibitor with anticancer activity. It inhibits EZH2 WT, EZH2 Y641N, and EZH1 with IC50s of 0.24 nM, 0.51 nM, and 6.1 nM, respectively. CPI-169 exhibits excellent antiproliferative activity and high in vivo antitumor efficacy in a NHL xenograft model.

Biological Activity I Assay Protocols (From Reference)

ln Vitro

In vitro activity: In KARPAS-422 cells, CPI-169 shows a dose-dependent inhibitory effect on cell viability, and produces synergy anti-proliferative activity when used in combination with ABT-199. In 16 out of 25 NHL cell lines, CPI-169 also suppresses cell growth with GI50 of<5 μM.

Kinase Assay: Compound potency is also assessed through incorporation of 3H-SAM into a biotinylated H3 peptide. Specifically, PRC2 containing either EZH1 (160 pM), wt EZH2 (40 pM), or Y641N mutant EZH2 (80 pM, both EZH2 prepared in-house) is pre-incubated with 3H-SAM (0.9 µM), 2 µM H3K27me3 activating peptide (H2N-RKQLATKAAR(Kme3)SAPATGGVKKP-amide) and compounds (as 10 point duplicate dose response titrations) for 120 min in a buffer consisting of 50 mM Tris (pH 8.5), 1 mM DTT, 0.07 mM Brij-35, 0.1% BSA, and 0.8% DMSO in a total volume of 12.5 µl in a black 384 well plate. Reaction is initiated with biotinylated H3 substrate peptides (H3K27me1 for wt EZH2, H3K27me2 for Y641N mutant EZH2; H2N-RKQLATKAAR(Kmen)SAPATGGVKKP-NTPEGBiot) as a 2 µM stock in 12.5 µL and allowed to react at room temperature for 5 h. Quenching is accomplished by addition of 20 µl of STOP solution (50 mM Tris (pH 8.5), 200 mM EDTA, 2 mM SAH). 35 µL of the quenched solution is transferred to Streptavidin Flashplates, incubated overnight, washed, and read in a TopCount Reader. For titrations all compound dilutions are in DMSO, final DMSO concentrations are 0.8% (v/v), and turnover is kept to less than < 5%. IC50s are calculated using non-linear least square four parameter fits (GraphPad 6.0).

Cell Assay: Relative cell numbers are assessed by Cell Titer-Glo (CTG) luminescent cell viability assay using an Envision instrument. GraphPad Prism 6.0 is used for curve fitting, IC50/GI50 and Hill coefficient (H) calculations. The GI90 is calculated using the formula: EC90 = (90 /100-90)1/H * EC50. Cell line: 25 NHL cell lines

ln Vivo

In mice bearing KARPAS-422 xenografts, CPI-169 (200 mg/kg, s.c.) effectively suppresses H3K27me3 levels and results in lymphoma tumor regression without affecting body weight or causing any overt adverse effects.

Animal Protocol

Dissolved in 10% DMSO + 60% polytheylene glycol 400 + 30% ddH2O; 200 mg/kg; s.c. injection

Mice bearing KARPAS-422 subcutaneous xenografts

References

Chem Biol.2014 Nov 20;21(11):1463-75.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C27H36N4O5S

Molecular Weight

528.66

CAS #

1450655-76-1

Related CAS #

1450655-76-1

SMILES

O=C(C1=C(C)N(C(C2CCN(S(=O)(CC)=O)CC2)C)C3=C1C=CC=C3)NCC4=C(OC)C=C(C)NC4=O

Synonyms

CPI 169; CPI169; CPI-169;(R,Z)-1-(1-(1-(ethylsulfonyl)piperidin-4-yl)ethyl)-N-((2-hydroxy-4-methoxy-6-methylpyridin-3-yl)methyl)-2-methyl-1H-indole-3-carbimidic acid

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (189.1 mM)

Water:<1 mg/mL

Ethanol:100 mg/mL (189.1 mM)

Solubility (In Vivo)

10% DMSO+60% PEG 400+30% ddH2O: 30mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8916 mL	9.4579 mL	18.9157 mL
	5 mM	0.3783 mL	1.8916 mL	3.7831 mL
	10 mM	0.1892 mL	0.9458 mL	1.8916 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

Calculate Reset

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Calculate Reset

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Calculate Reset

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Calculate Reset

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make 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 in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

Calculate Reset

Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Biological Data

Enhancer of Zeste Homolog 2 Inhibitors Cause Cell Killing in Various NHL Subtypes. Chem Biol. 2014, 21(11), 1463-1475.