PRT062607

Inhibitor of SYK

Structure

Information

  • SYK
  • Inhibitor

In Vitro Validations

Uniprot ID: P43405
Target Class: Protein kinase
Target SubClass: TK
Potency: IC50
Potency Value: 2.1 nM
Potency Assay: Radiometric assay; in a FRET-based assay, IC50 = 6 nM
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Tyrosine-protein kinase SYK, SYK, KSYK_HUMAN, p72- ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 FGR 81 nM, MLK1 88 nM, YES 123 nM, FLT3 139 nM, PAK5 166 nM, LYN 192 nM, SRC 244 nM, LCK 249 nM, PYK2 108 nM
Potency assay (off target): Radiometric assay. At 50 nM, P505-15 was selective for SYK over 270 other kinases; at 300 nM, it inhibited 8 additional kinases >80%.
Potency assay, off target (cells): No activity was detected against LYN substrates in B cells.
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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

I recommend this compound as "best available" for use in cells; it is potent and cell active and almost meets a high bar for selectivity when broadly profiled. I also recommend this compound as "best available" for use in mice and rats. The original publication shows the PK data and use of the compound in in vivo models.

(last updated: 6 May 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

P505-15 is a small molecule, and a potent and selective inhibitor of SYK. It inhibits SYK and suppresses BCR signaling in SUDHL4 cells and inhibits SYK-dependent signaling in human whole blood. P505-15 reversibly inhibited SYK in mice after oral dosing.

(last updated: 10 Sept 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Highly selective inhibitor of Spleen Tyrosine Kinase (SYK). Exhibits ~80-fold selectivity for SYK over the next target. Shows 1 nM potency against SYK, with substantially lower potency towards the three related kinases PTK2 (415 nM), PTK2B (108 nM), and ZAP70 (1050 nM). Potently inhibits SYK activity in cells without interfering with its activation. Potently and selectively inhibits SYK-mediated signaling in human whole blood. Orally available, with dose-dependent anti-inflammatory activity in rodent models at doses that specifically suppress SYK activity.

(last updated: 28 Apr 2017 )