PZ2891

PZ2891 : Modulator of PANK1, PANK2 and PANK3, acting as allosteric activator and orthosteric inhibitor

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe PZ2891 is in the process of SERP review.

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Information

PANK1
PANK2
PANK3

Allosteric Activator, Orthosteric Inhibitor

up to 10 uM

DOI - 10.1038/s41467-018-06703-2

Probe Availability:

In Vitro Validations

Uniprot ID: Q8TE04

Target Class: Kinase

Target SubClass: Pantothenate kinase

Potency: IC50

Potency Value: 40.2 ± 4.4 nM

Potency Assay: SPR, radiochemical kinase assay

PDB ID for probe-target interaction (3D structure): 6B3V

Structure-activity relationship: yes

Target aliases:

Pantothenate kinase 1, PANK, PANK1, PANK1_HUMAN, h ...

DOI Reference: 10.1038/s41467-018-06703-2

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

PZ-2891 did not have significant inhibitory activity in a screen of 468 mammalian kinases.

Outside Target Family: A screen on 72 cellular proteins known to cause off-target effects in drug discovery highlighted that PZ-2891 selectively target PANK in cells and indicated the absence of off-target pharmacological interactions.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

I recommend PZ-2891 is a chemical probe for the PANK family, particularly for studying activation effects. PZ-2891 has an intriguing mechanism of action where it serves as either an orthosteric inhibitor or allosteric activator depending upon the dose. It binds at the dimer interface between PANK protomers. If one protomer is occupied and inhibited, the second protomer becomes constitutively activated and also less sensitive to product inhibition, thus facilitating a strong activation effect. This unique MOA and chemotype also provides excellent selectivity for the PANKs over the protein kinases and many potential anti-targets outside of the kinase family. PZ-2891 can be used as a chemical probe both in cultured cells and also in mouse models, and also benefits from the availability of a suitable control ligand, P-3067.

(last updated: 11 Oct 2021 )