Home Angiogenesis Syk inhibitor - Pyk2 inhibitor - FAK inhibitor - PAK inhibitor - Src inhibitor - Mixed Lineage Kinase inhibitor - FLT3 inhibitor PRT062607 (P505-15) HCl For research use only.

PRT062607 (P505-15) HCl

Synonyms: BIIB057, PRT-2607

PRT062607 (P505-15, BIIB057, PRT-2607) HCl is a novel, highly selective Syk inhibitor with IC50 of 1 nM in cell-free assays, >80-fold selective for Syk than Fgr, PAK5, Lyn, FAK, Pyk2, FLT3, MLK1 and Zap70.

PRT062607 (P505-15) HCl Chemical Structure

PRT062607 (P505-15) HCl Chemical Structure

CAS No. 1370261-97-4

Purity & Quality Control

PRT062607 (P505-15) HCl Related Products

Signaling Pathway

Syk Signaling Pathways

Syk Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Ramos Function assay Inhibition of Syk in anti IgM-stimulated human Ramos cells assessed as BLNK phosphorylation by cellular assay, IC50 = 0.178 μM. 24726806
Ramos B Function assay 30 mins Inhibition of Syk in anti-igM stimulated human Ramos B cells assessed as phospho-BLNK level preincubated for 30 mins followed by anti-IgM stimulation measured after 15 mins by flow cytometric analysis, IC50 = 0.178 μM. 25633741
Ramos B Function assay 30 mins Inhibition of Syk in anti-igM stimulated human Ramos B cells assessed as phospho-BLNK level preincubated for 30 mins followed by anti-IgM stimulation measured after 15 mins by flow cytometric analysis, IC50 = 0.178 μM. 26320624
Ramos Cytotoxicity assay Cytotoxicity against human Ramos cells, IC50 = 0.223 μM. 23151054
Ramos Function assay Inhibition of SYK in human Ramos cells, IC50 = 0.223 μM. 23350847
Jurkat T Function assay 30 mins Inhibition of ZAP70 in anti-CD3 stimulated human Jurkat T cells assessed as SLP76 phosphorylation at Y128 preincubated for 30 mins followed by anti-CD3 stimulation measured after 2 mins by FACS analysis, IC50 = 1.805 μM. 25633741
bone marrow cells Cytotoxicity assay 4 days Cytotoxicity against C57BL/6 mouse bone marrow cells assessed as growth inhibition preincubated for 4 days followed by [3H]-thymidine addition measured after 5 hrs by betaplate counting analysis, IC50 = 5.853 μM. 25633741
bone marrow cells Function assay Inhibition of IL3 dependent proliferation in C57/B16 mouse bone marrow cells using [3H]thymidine by liquid scintillation counting, IC50 = 5.853 μM. 24726806
CHO Function assay Inhibition of human ERG expressed in CHO cells by automated Qpatch clamp assay, IC50 = 8.6 μM. 25633741
Click to View More Cell Line Experimental Data

Biological Activity

Description PRT062607 (P505-15, BIIB057, PRT-2607) HCl is a novel, highly selective Syk inhibitor with IC50 of 1 nM in cell-free assays, >80-fold selective for Syk than Fgr, PAK5, Lyn, FAK, Pyk2, FLT3, MLK1 and Zap70.
Targets
Syk [1]
(Cell-free assay)		 FGR [1]
(Cell-free assay)		 MLK1 [1]
(Cell-free assay)		 PYK2 [1]
(Cell-free assay)		 YES [1]
(Cell-free assay)		 Click to View More Targets
1 nM 81 nM 88 nM 108 nM 123 nM
In vitro
In vitro PRT062607(P505-15) anti-SYK activity is at least 80-fold greater than its affinity for other kinases. at least 80-fold greater than its affinity for other kinases. PRT062607 potently inhibits B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM). [1] PRT062607 inhibits BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and beneath stromal cells. PRT062607 furthermore inhibits Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering. [2]
Kinase Assay fluorescence resonance energy transfer (FRET) assay
The extent of substrate phosphorylation by Syk is measured in the presence of various PRT062607 concentrations. Syk activity is determined by a fluorescent antibody specific for phosphorylated tyrosine by using the increase of FRET. Twelve concentrations are tested for dose response. Specificity and potency of kinase inhibition is determined by evaluation of PRT062607 in the Millipore KinaseProfiler panel of 270 independent purified kinase assays. For profiling, PRT062607 is tested in duplicate at two concentrations at a fixed concentration of ATP. Subsequently, IC50 determinations using the radioactive assays are carried out at an ATP concentration optimized for each individual kinase. All radioactive ATP incorporationenzyme assays are performed at Millipore.
Cell Research Cell lines Syk-dependent BaF3 cell
Concentrations ~6 μM
Incubation Time 3 days
Method

CellTiter Glo
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-Syk / Syk / p-FLT3 / FLT3 / p-STAT5 / STAT5 Bcl6 24525236
Growth inhibition assay Cell viability 28064214
In Vivo
In vivo The pharmacokinetic/pharmacodynamic relationship predicted that 70% Syk suppression is maintained in mice over a 24h period after 30 mg/kg dosing. At 15 mg/kg, Syk inhibition ranges from 7.5% (Cmin) to 78.4% (Cmax) with an average inhibition of 67% over 24 h. Oral administration of PRT062607 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. Statistically significant efficacy is observed at concentrations that specifically suppressed Syk activity by 67%.[1]
Animal Research Animal Models Mouse Collagen Antibody-Induced Arthritis Model
Dosages 5, 15, 30 mg/kg, b.i.d.
Administration Oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01652937 Withdrawn
Rheumatoid Arthritis
Biogen
 August 2012 Phase 2

Chemical Information & Solubility

Molecular Weight 429.91 Formula

C19H23N9O.HCl
CAS No. 1370261-97-4 SDF Download PRT062607 (P505-15) HCl SDF
Smiles C1CCC(C(C1)N)NC2=NC=C(C(=N2)NC3=CC(=CC=C3)N4N=CC=N4)C(=O)N.Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 86 mg/mL ( (200.04 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 86 mg/mL

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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