PFI-5

PFI-5 : inhibitor of SMYD2

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Probe PFI-5 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

SMYD2

mixed interaction mode

1-3 uM

Additional Data

SGC Chemical Probe Collection

In Vitro Validations

Uniprot ID: Q9NRG4

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: IC50

Potency Value: 16 nM

Potency Assay: SMYD2 Activity Assay with 20 uM SAM

PDB ID for probe-target interaction (3D structure): 6CBY

Target aliases:

N-lysine methyltransferase SMYD2, KMT3C, SMYD2, SM ...

DOI Reference: 10.1021/acs.jmedchem.9b00112

Uniprot ID: Q9NRG4

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: IC50

Potency Value: 8 nM

Potency Assay: SMYD2 Activity Assay with 70 nM SAM

PDB ID for probe-target interaction (3D structure): 6CBY

Target aliases:

N-lysine methyltransferase SMYD2, KMT3C, SMYD2, SM ...

DOI Reference: 10.1021/acs.jmedchem.9b00112

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Within target family: Biochemical selectivity across a wide number of SAM-dependent methyltransferases was performed across a panel of 35 targets including PKMTs, PRMTs, DNMTs, and RNAMTs. The PKMTs SUV420H1 and SUV420H2 were biochemically inhibited at 1 μM. Outside target family: PFI-5 was also run against a panel of 15 diverse protein targets and 40 kinases.

Potency assay, off target (cells): PFI-5 was investigated in a cellular H4K20me1 methylation assay in MCF7 cells and no significant effect on methylation was seen up to 50 μM, leaving a 30-fold selectivity window for cellular use of PFI-5 in the context of SMYD2 versus SUV420H1 and SUV420H2.

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

PFI-5 is a quality chemical probe with a good negative control and together with BAY-598 has the cellular biology of SMYD2 covered. There is clearly sufficient data to suggest PFI-5 cleanly targets SMYD2 in cells at the suggested concentration of 1-3 uM and there should be no hesitation to utilize this chemical probe, in particular with its enantiomer serving as an excellent control and the very orthogonal probe from Bayer that should eliminate any concerns that an observed phenotype is caused by a target other then SMYD2.

(last updated: 21 Feb 2023 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

No stability assay, protein binding or DMPK data are shown. Data regarding toxicity, hidden in the supplement, indicate a small experimental window.

(last updated: 22 Mar 2023 )