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PRT062607 (P505-15; PRT-2607) is an orally active ATP-competitive Syk inhibitor with an IC50 value of 1 nM, and exhibits at least 80-fold selectivity over other kinases. PRT062607 blocks B cell antigen receptor-mediated activation, Fcε receptor 1-mediated basophil degranulation and microglial phagocytosis, and induces caspase-dependent apoptosis and microglial death. PRT062607 inhibits tumor growth and peripheral nerve injury-induced mechanical allodynia, and prevents neuronal loss. PRT062607 can be used in research related to rheumatoid arthritis, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, neurodegenerative diseases and neuropathic pain.
For research use only. We do not sell to patients.
PRT062607 (P505-15; PRT-2607) is an orally active ATP-competitive Syk inhibitor with an IC50 value of 1 nM, and exhibits at least 80-fold selectivity over other kinases. PRT062607 blocks B cell antigen receptor-mediated activation, Fcε receptor 1-mediated basophil degranulation and microglial phagocytosis, and induces caspase-dependent apoptosis and microglial death. PRT062607 inhibits tumor growth and peripheral nerve injury-induced mechanical allodynia, and prevents neuronal loss. PRT062607 can be used in research related to rheumatoid arthritis, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, neurodegenerative diseases and neuropathic pain[1][2][3][4].
Cellular Effect
Cell Line
Type
Value
Description
References
Bone marrow cell
IC50
5853 nM
Compound: 1, BIB-057
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
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
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
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
PRT062607 potently inhibits purified Syk in FRET kinase assays containing 15 and 100 μM ATP, with IC50 values of 2.1 and 6 nM[1]. PRT062607 (0.01-2.5 μM; 1.5 h) specifically inhibits BCR-mediated Syk-dependent BLNK Tyr84 phosphorylation in SUDHL4 cells, with an IC50 of 0.16-0.4 μM[1]. PRT062607 potently inhibits BCR-mediated Syk-dependent ERK Tyr204 phosphorylation in Ramos cells with an IC50 of 50 nM; at concentrations up to 2 μM, this compound does not affect non-Syk-dependent, PMA-mediated ERK phosphorylation[1]. PRT062607 (P505-15) (0-6 μM; 3 days) selectively inhibits the proliferation of Syk-dependent TEL-Syk Ba/F3 cells, with an IC50 of 120 nM[1]. PRT062607 (0-4 μM; 40 min) potently inhibits Syk-dependent BCR-mediated ERK Tyr204 phosphorylation in human whole blood B cells, with a mean IC50 of 0.27 μM[1]. PRT062607 (0-4 μM; 16.5 h) potently inhibits Syk-dependent BCR-mediated B cell activation (CD69 upregulation) in human whole blood, with a mean IC50 of 0.28 μM[1]. PRT062607 (0-4 μM; 1.25 h) potently inhibits Syk-dependent FcεR1-mediated basophil degranulation in human whole blood, with a mean IC50 of 0.15 μM[1]. PRT062607 (2 μM; 30 min) inhibits anti-IgM-induced autophosphorylation of SYK in Ramos human non-Hodgkin's lymphoma B cells[2]. PRT062607 (0.02-2 μM; 30 min) inhibits anti-IgM-induced phosphorylation of ERK and AKT in the human non-Hodgkin's lymphoma B cell line Ramos in a concentration-dependent manner, with an IC50 of approximately 50 nM, and achieves complete inhibition at 250 nM[2]. PRT062607 (1-3 μM; 72 hours) induces apoptosis in human non-Hodgkin's lymphoma B cell lines SU-DHL4, SU-DHL6 and Ramos with functional BCR signaling, but exerts no such effect in BCR/BLNK-deficient Toledo/Karpas-422 cell lines or primary human B cells; PRT062607 (1 μM; 24 hours) induces apoptosis in SU-DHL6 cells mixed with whole blood, while primary B cells remain unaffected[2]. PRT062607 (0.01-1 μM; 30 min) concentration-dependently inhibits BCR-induced AKT phosphorylation in primary human chronic lymphocytic leukemia (CLL) cells, with complete inhibition achieved at concentrations ranging from 0.3 to 1 μM[2]. PRT062607 (10 nM-10 μM; 72 h) reduces cell viability by 36% in primary human chronic lymphocytic leukemia (CLL) samples, including high-risk samples with 17p deletion, 11q deletion or unmutated IgVh, with an IC50 < 3 μM in responsive samples[2]. PRT062607 (10 nM-10 μM; 72 h) acts synergistically with fludarabine to reduce the viability of primary human chronic lymphocytic leukemia (CLL) cells, and a fludarabine hyporeactive effect is observed at lower fludarabine concentrations[2]. PRT062607 (10 μM; 3 d) completely blocks LPS (HY-D1056)-induced neuronal loss as well as spontaneous age-related neuronal loss in primary rat cerebellar neuron-glia cultures[3]. PRT062607 (10 μM; 3 d) significantly depletes microglia and induces microglial death in primary rat cerebellar neuron-glia cultures without LPS treatment, but does not deplete microglia in LPS-treated cultures[3]. PRT062607 (10 μM; 24 h) induces significant microglial necrosis and apoptotic cell death, and reduces total cell density in primary rat cortical microglia[3]. PRT062607 (10 μM; overnight) reduces the phagocytosis of 5 μm microspheres by primary rat cortical microglia under both resting and LPS-activated conditions[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Inhibited BCR-mediated BLNK Tyr84 phosphorylation in a concentration-dependent manner, with an IC50 range of 0.16-0.4 μM. Did not inhibit BCR-mediated Syk Tyr352 phosphorylation at concentrations up to 2.5 μM.
Ba/F3 mouse pro-B cell line stably expressing TEL-Syk
Concentration:
0.074, 0.22, 0.66, 2 and 6 μM
Incubation Time:
3 days
Result:
Selectively inhibited proliferation of the TEL-Syk-expressing Ba/F3 cell line with an IC50 of 120 ± 5 nM. Did not inhibit proliferation of Ba/F3 cell lines expressing TEL-JAK1, TEL-JAK2, TEL-JAK3, TEL-Tyk2, or TEL-Zap70 at 2 μM.
SU-DHL4, SU-DHL6, Ramos, Toledo, and Karpas-422 human non-Hodgkin lymphoma B-cell lines; primary human B-cells
Concentration:
1 μM (24 h whole blood experiment); 1 μM, 3 μM (72 h apoptosis assay)
Incubation Time:
24 h (whole blood experiment); 72 h (apoptosis assay)
Result:
Induced apoptosis (measured by active caspase-3 cleavage) in BCR-signaling competent cell lines SU-DHL4, SU-DHL6, and Ramos, but not in BCR-deficient Toledo or BLNK-deficient Karpas-422 lines. Induced apoptosis in SU-DHL6 cells mixed with heparinized human whole blood, while primary B-cells did not undergo apoptosis.
PRT062607 (5-30 mg/kg; p.o.; twice daily; for 10-15 days) dose-dependently inhibits joint inflammation in collagen antibody-induced arthritis models of mice and rats[1]. PRT062607 (15 mg/kg; p.o.; twice daily; 5 days) significantly inhibits B cell receptor (BCR)-induced splenomegaly and marginal B cell zone expansion in mice[2]. PRT062607 (10-20 mg/kg; p.o.; twice daily; 5 weeks) significantly inhibits the growth of Ramos NHL tumors in NOD/SCID mice[2]. PRT062607 (4.5 mg per rat; intrathecal injection; single administration) significantly reverses mechanical allodynia induced by spared nerve injury in rats[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Produced average paw inflammation score inhibitions of 12%, 44%, and 87% respectively, with corresponding average plasma concentrations of 0.38, 0.95, and 1.47 μM. Significantly reduced blinded histopathology scores and hind paw ankle thickness in the 15 and 30 mg/kg dose groups compared with vehicle controls. Rendered joint structure indistinguishable from normal naive mice at 30 mg/kg, with no intra-articular neutrophils, fibrin, or synovial tissue damage.
Completely suppressed inflammation in 7 of 8 rats at 15 mg/kg, resulting in a mean inflammation score of 0.63 with an average plasma concentration of 1.34 μM. Produced a significantly efficacious reduction in inflammation at 10 mg/kg with an average plasma concentration of 0.72 μM. Significantly reduced blinded histopathology scores and hind paw ankle thickness in the 15 mg/kg dose group compared with vehicle controls. Rendered joint morphology indistinguishable from normal naive rats at 15 mg/kg, with no inflammatory infiltrate, synovial hyperplasia, or cartilage erosion.
Reduced average tumor weight. Sustained steady-state tumor concentrations above 63 nM (10 mg/kg), 176 nM (15 mg/kg), and 325 nM (20 mg/kg) over the entire dosing interval. Increased lymphocyte counts in 15 mg/kg group; no reductions in any leukocyte subsets across all dose groups.
Animal Model:
Sprague Dawley (male and female, 7-8 weeks old, n=6 per sex per treatment group)[4]
Dosage:
4.5 mg
Administration:
intrathecal injection; single injection
Result:
Significantly reversed SNI-induced mechanical pain hypersensitivity in both male and female rats.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (254.16 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.5416 mL
12.7081 mL
25.4162 mL
5 mM
0.5083 mL
2.5416 mL
5.0832 mL
10 mM
0.2542 mL
1.2708 mL
2.5416 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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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.
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (50.0 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 (6.35 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 μLDMSO 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.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.35 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
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.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
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).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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.
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