CPI-169

Reagent Authentication Certificate:

Chemical Probes Portal CPI-169.pdf

Protein target name:

EZH1, EZH2

Mechanism of action:

SAM competitive inhibitor

Recommended Concentration for use in cells:

Up to 500 nM

Probe Availability

MedChem Express (CPI-169)

Cayman (1450655-76-1)

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Protein methyltransferase

HUGO ID:

HGNC:3527 HGNC:3526

Entrez gene ID:

2146 2145

UNIPROT ID:

Q15910 Q92800

Target alias:

WVS; ENX1; EZH1; KMT6; WVS2; ENX-1; EZH2b; KMT6A, enhancer of zeste 2 polycomb repressive complex 2 subunit, KMT6B, enhancer of zeste 1 polycomb repressive complex 2 subunit

Probe Details

Chemical Probes Portal ID:

CPP633

Probe alias:

CPI-169 R-enantiomer; CPI-169; 1802175-07-0; HY-15956A; AKOS025404937; CS-3174

PubChem CID:

71712226

SMILES string:

CCS(=O)(=O)N1CCC(CC1)[C@@H](C)N2C(=C(C3=CC=CC=C32)C(=O)NCC4=C(C=C(NC4=O)C)OC)C

InChi Key:

LHGUZCKPFXXVPV-GOSISDBHSA-N

Orthogonal probe:

UNC1999EPZ011989

Physico-chemical properties

NMR:

1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 7.82-7.66 (m, 2H), 7.62 (d, J = 7.8, 1H), 7.17-6.99 (m, 2H), 6.15 (s, 1H), 4.32 (d, J = 5.1 Hz, 2H), 4.25 - 4.15 (m, 1H), 3.84 (s, 3H), 3.73 - 3.65
(m, 1H), 3.45 - 3.36 (m, 1H), 2.98 (q, J = 7.4 Hz, 2H), 2.87 - 2.77 (m, 1H), 2.60 (s, 3H), 2.54-2.45 (m, 1H), 2.42 - 2.30 (m, 1H), 2.20 (s, 3H), 2.06 - 1.97 (m, 1H), 1.58 - 1.48 (m, 3H), 1.42 - 1.31 (m, 1H), 1.17 (t, J = 7.4 Hz, 3H), 1.13 - 1.00 (m, 1H), 0.83 - 0.73 (m, 1H)

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

EZH2 0.24 nM, Y641NEZH2 0.5 nM, EZH1 6.4 nM

Potency assay:

PRC2 enzyme inhibition assay

Off target activity

Potency assay (off target):

No activity was detected against a panel of 30 protein methyltransferases with the exception of EZH2 and EZH1.

Probe Selectivity in Vitro:

Not available

In cell validation

On target activity in cells

Potency in cells:

EC50

41 nM

Potency assay (cells):

ELISA-based detection of inhibition of protein substrate (H3K27) methylation

Target engagement assay (cells):

CETSA

In vivo validation

Organism:

Mouse

Dose:

50-200 mg/kg

Route of delivery:

Subcutaneous

Organ of Interest

Organ (O):

KARPA-422 xenograft

Target engagement assay:

Indirect, inhibition of protein substrate (H3K27) methylation in tumors.

Primary Reference

Reference (doi):

10.1016/j.chembiol.2014.09.017

Reference (PMID):

25457180

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

Jul 31 2016 - 4:53pm

CPI-169 is a member of a family of structurally related, pyridone based EZH2 inibitors that also includes compounds such as UNC1999 and GSK-343. With the exception of EZH1, CPI-169 is highly selective and is suitable for both in vitro cell assays and in vivo work. The compound is not orally biovailable; however, in vivo PD modulation and efficacy in a tumor xenograft model was demonstated using subcutaneous administraton via a a twice daily dosing.

Aug 19 2016 - 8:52pm

Subcutaneous treatment with CPI-169 (200 mg/kg twice daily) in KARPAS-422 mouse xengraft model showed >60%% tumor growth inhibition after 28 days.

Sep 9 2016 - 5:12pm

CPI-169

Probe Availability

Probe Information

Target Details

WVS; ENX1; EZH1; KMT6; WVS2; ENX-1; EZH2b; KMT6A, enhancer of zeste 2 polycomb repressive complex 2 subunit, KMT6B, enhancer of zeste 1 polycomb repressive complex 2 subunit

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?

Search form

CPI-169

Probe Availability

Probe Information

Target Details

WVS; ENX1; EZH1; KMT6; WVS2; ENX-1; EZH2b; KMT6A, enhancer of zeste 2 polycomb repressive complex 2 subunit, KMT6B, enhancer of zeste 1 polycomb repressive complex 2 subunit

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?