2. Protein Tyrosine Kinase/RTK
  3. Syk
  4. PRT062607 Hydrochloride

PRT062607 Hydrochloride  (Synonyms: P505-15 Hydrochloride)

Cat. No.: HY-15323 Purity: 98.68%
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PRT062607 Hydrochloride (P505-15 Hydrochloride) is a highly specific and potent inhibitor of purified Syk (IC50 1-2 nM).

For research use only. We do not sell to patients.

PRT062607 Hydrochloride Chemical Structure

PRT062607 Hydrochloride Chemical Structure

CAS No. : 1370261-97-4

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 172 In-stock
Solution
10 mM * 1 mL in DMSO USD 172 In-stock
Solid
5 mg USD 156 In-stock
10 mg USD 238 In-stock
25 mg USD 420 In-stock
50 mg USD 634 In-stock
100 mg USD 980 In-stock
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500 mg   Get quote  

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Customer Review

Based on 3 publication(s) in Google Scholar

Other Forms of PRT062607 Hydrochloride:

PRT062607 Hydrochloride Related Antibodies

Top Publications Citing Use of Products

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

PRT062607 Hydrochloride (P505-15 Hydrochloride) is a highly specific and potent inhibitor of purified Syk (IC50 1-2 nM).

IC50 & Target

IC50: 1 nM (Syk), 81 nM (Fgr), 88 nM (MLK1), 123 nM (Yes)[1]
In Vitro

PRT062607 (P505-15) is a novel, highly specific, and potent orally available small-molecule inhibitor of Syk. The potency of PRT062607 against its target kinase Syk is initially tested in two different purified kinase assays. Using a FRET assay, half-maximal Syk inhibition required 6±0.2 nM (mean±S.E.M.). Similar potency is observed when tested in a radioactive enzyme assay, with a resulting Syk IC50 of 2.1±0.4 nM (mean±S.E.M.). In human whole blood, 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PRT062607 Hydrochloride Related Antibodies
In Vivo

In the mouse CAIA model, oral administration of PRT062607 (P505-15) results in an average inhibition of paw inflammation, as measured by daily scoring of inflammation compared with vehicle controls, of 12, 44, and 87% with average plasma concentration (C average over 24 h) assessed at the end of the study of 0.38, 0.95, and 1.47 μM, respectively. In mice treated with 30 mg/kg PRT062607, the damage to the joints is significantly reduced and seemed indistinguishable from normal mice. In the rat CIA model, the high dose of PRT062607 (15 mg/kg b.i.d.) completely suppresses inflammation in a majority of the animals (seven of eight), by the end of the study (mean inflammation score±S.E.M.=0.63±1.1; p<0.0001 versus vehicle)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
Molecular Weight

429.91

Formula

C19H24ClN9O
CAS No.
Appearance

Solid

Color

Light yellow to khaki

SMILES

NC(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(N4N=CC=N4)=C3)=O.[H]Cl
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

H2O : ≥ 50 mg/mL (116.30 mM)

DMSO : ≥ 33 mg/mL (76.76 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.3261 mL 11.6303 mL 23.2607 mL
5 mM 0.4652 mL 2.3261 mL 4.6521 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (5.82 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (5.82 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  PBS

    Solubility: 50 mg/mL (116.30 mM); Clear solution; Need ultrasonic

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).
Purity & Documentation

Purity: 98.68%

COA (257 KB) LCMS (268 KB)

Handling Instructions (2659 KB)
References
Kinase Assay
[1]

Potency of Syk inhibition is determined by using a fluorescence resonance energy transfer (FRET) assay. The extent of substrate phosphorylation by Syk is measured in the presence of various PRT062607 (P505-15) 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 Kinase Profiler 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 incorporation enzyme assays are performed[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay
[1]

SUDHL4 cells (106 cells) are stimulated for 30 min with F(ab)′2 anti-human IgM antibody. Signaling is terminated by resuspending cells in ice-cold lysis buffer (50 mM Tris, pH 7.4, 150 mM NaCl, 0.5 mM EDTA, 1% nonidet P-40, and 0.5% sodium deoxycholate) containing freshly added protease and phosphatase inhibitor tablets. Protein lysates are resolved by SDS-polyacrylamide gel electrophoresis under reducing conditions and probed with the indicated antibodies. Secondary antibody conjugated to horseradish peroxidase and enhanced chemiluminescence detection reagent are used for the detection of specific protein. Where indicated, cells are pretreated for 1 h at 37°C with PRT062607 or vehicle control before stimulation. Densitometry of exposed films is performed by using the AlphaImager 2200. Ba/F3 cells are seeded at 5000 cells per well in a 384-well tissue culture plate containing media with various concentrations of PRT062607 or staurosporin. After 3 days, viability of cells is quantitated by CellTiter Glo following the manufacturer-supplied protocols[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
Female BALB/c mice receive a single oral dose of 15 or 30 mg/kg PRT062607 and are anesthetized with a subcutaneous ketamine cocktail, and blood is harvested via cardiac puncture at 0.5, 1, 2, 3, 4, 5, 6, 8, and 24 h postdose, (n=3/time point; n=8 vehicle controls). Blood is dispensed into three heparin-containing tubes, one for determination of drug concentration and the remaining two for ex vivo stimulation with isotype control or anti-mouse IgD antibody for 10 min. Blood is processed for intracellular phospho-flow cytometry to evaluate BCR signaling as described earlier; mouse B cells are detected by using CD45R-B220 PerCP-conjugated antibody. Plasma samples are analyzed for PRT062607 concentration by using a liquid chromatography tandem mass spectrometer. The analytical range is 2 to 5000 ng/mL.
Rats[1]
Collagen-induced arthritis (CIA) is induced in female, 7-week old Lewis rats by subcutaneous injection of bovine collagen II emulsified with incomplete Freund's adjuvant at the base of the tail. On day 10, the rats are boosted with a second subcutaneous injection. PRT062607 administration is initiated when at least one hind paw is inflamed (inflammation score 1), and enrollment into a treatment group is designated as day 1 of the study for each individual animal (n=8/dose group). Progression of disease is evidenced by increased edema and erythema of one or both ankle joints, followed by the involvement of the metatarsal and interphalangeal joints. Fully developed arthritis is observed approximately 4 to 7 days after the onset of inflammation. Hind paws (sum of two paws) are scored daily for progression of inflammation. Inflammation scores for each paw are determined based on the following scale: 0, normal; 1, mild, but definite redness and swelling of the ankle possibly limited to individual digits; 2, moderate redness and swelling of ankle; 3, severe redness and swelling of the entire paw including digits; and 4, maximally inflamed limb with involvement of multiple joints. Ankle thickness measurements are obtained by a caliper device. At study termination, rats are anesthetized, and blood is harvested by cardiac puncture for complete blood counts and drug plasma concentration.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO / H2O 1 mM 2.3261 mL 11.6303 mL 23.2607 mL 58.1517 mL
5 mM 0.4652 mL 2.3261 mL 4.6521 mL 11.6303 mL
10 mM 0.2326 mL 1.1630 mL 2.3261 mL 5.8152 mL
15 mM 0.1551 mL 0.7754 mL 1.5507 mL 3.8768 mL
20 mM 0.1163 mL 0.5815 mL 1.1630 mL 2.9076 mL
25 mM 0.0930 mL 0.4652 mL 0.9304 mL 2.3261 mL
30 mM 0.0775 mL 0.3877 mL 0.7754 mL 1.9384 mL
40 mM 0.0582 mL 0.2908 mL 0.5815 mL 1.4538 mL
50 mM 0.0465 mL 0.2326 mL 0.4652 mL 1.1630 mL
60 mM 0.0388 mL 0.1938 mL 0.3877 mL 0.9692 mL
H2O 80 mM 0.0291 mL 0.1454 mL 0.2908 mL 0.7269 mL
100 mM 0.0233 mL 0.1163 mL 0.2326 mL 0.5815 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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PRT062607 Hydrochloride Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PRT0626071370261-97-4P505-15PRT 062607PRT-062607SykSpleen tyrosine kinaseInhibitorinhibitorinhibit

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