Spastazolin

Spastazolin : ATP competitive of SPAST

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe Spastazolin is in the process of SERP review.

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Information

SPAST

ATP competitive

up to 10 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: Q9UBP0

Target Class: Enzyme

Target SubClass: ATPase

Potency: IC50

Potency Value: 99 ± 18 nM

Potency Assay: Inhibition of recombinant h-spastin

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

Target aliases:

Spastin, SPG4, KIAA1083, FSP2, ADPSP, SPAST, SPAST ...

DOI Reference: 10.1038/s41589-019-0225-6

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Selectivity within target family: Spastazoline did not appreciably inhibit any of the four related AAA proteins. Selectivity outside target family: Tested against a panel of 65 Kinases, spastazoline only inhibited one of the 65 kinases tested (NTRK1) by >50%.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Based on the selectivity data provided, spastazoline appears to be quite selective for spastin among the 4 AAA proteins measured. That said, the off-target kinase activity against both Flt3 and NTRK1 (TRKA), when measured at 1 mM ATP as for the spastin assay, is only roughly 20-fold (0.1 uM for spastin vs 2 uM for Flt2 or NTRK1(TRKA). Based on the K1/2 values provided, at 1 mM ATP and 10 uM spastazoline, spastin should be inhibited 99%, but Flt3 or NTRK1(TRKA) should also be inhibited 83%, which may by itself be sufficient to impact the biological readout. Thus, my recommendation would be to test in parallel the appropriate kinase-selective probe(s) in order to accurately assess the role of spastin. I would also suggest a broader kinase profiling study be conducted for spastin to see if Flt3 and NTRK1(TRKA) are the only kinases that show relatively potent inhibition by this putative spastin probe molecule.

(last updated: 31 May 2023 )