CPI-169

Catalog No.S7616 Batch:S761601

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Technical Data

Formula

C27H36N4O5S
Molecular Weight 528.66 CAS No. 1450655-76-1
Solubility (25°C)* In vitro DMSO 100 mg/mL (189.15 mM)
Ethanol 100 mg/mL (189.15 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description CPI-169 is a potent, and selective EZH2 inhibitor with IC50 of 0.24 nM, 0.51 nM, and 6.1 nM for EZH2 WT, EZH2 Y641N, and EZH1, respectively.
Targets
EZH2 WT [1] EZH2 Y641N [1] EZH1 [1]
0.24 nM 0.51 nM 6.1 nM
In vitro 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. [1]
In 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. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Biochemical Assays

    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:[1]
  • Cell lines

    25 NHL cell lines

  • Concentrations

    ~10 μM

  • Incubation Time

    4 d

  • Method

    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.
Animal Study:[1]
  • Animal Models

    Mice bearing KARPAS-422 subcutaneous xenografts

  • Dosages

    200 mg/kg, BID

  • Administration

    s.c.

Selleck's CPI-169 has been cited by 10 publications

FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling [ J Exp Clin Cancer Res, 2023, 42(1):96] PubMed: 37085881
FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling [ J Exp Clin Cancer Res, 2023, 42(1):96] PubMed: 37085881
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226] PubMed: 36266272
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226] PubMed: 36266272
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2 [ Cell Chem Biol, 2021, S2451-9456(21)00213-0] PubMed: 33979649
The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis [ J Clin Invest, 2020, 134217] PubMed: 32701505
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143] PubMed: 33067904
SWI/SNF catalytic subunits' switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells. [ Nat Commun, 2018, 9(1):4116] PubMed: 30297712
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740] PubMed: 30135193
The Human Immunodeficiency Virus 1 ASP RNA promotes viral latency by recruiting the Polycomb Repressor Complex 2 and promoting nucleosome assembly. [ Virology, 2017, 506:34-44] PubMed: 28340355

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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