PRT062607 hydrochloride

SKU: orb1305152

Description

PRT062607 hydrochloride

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1370261-97-4
• MW: 429.91
• Purity: 97.11%
• Formula: C₁₉H₂₃N₉O·HCl
• SMILES: Cl.N[C@H]1CCCC[C@H]1Nc1ncc(C(N)=O)c(Nc2cccc(c2)-n2nccn2)n1
• Target: Syk,PYK2,MLK,FAK,Apoptosis,PAK,Src
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:45 mg/mL (104.67 mM);H2O:79 mg/mL (183.76 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.65 mM)

Bioactivity

• Target IC50:
  Syk:1 nM (cell free)|Lck:249 nM|PAK5:166 nM|MLK1:88 nM (cell free)|FGR:81 nM (cell free)
• In Vivo:
  Demonstrating a rapid onset of action, 0.5 h after oral administration of 30 mg/kg P505-15, Syk activity was reduced by 80% and nearly completely suppressed fo the Next 5 h relative to Vehicle control-treated mice. Syk activity remained more than 60% suppressed fo the first 8 h postdosing, returning to levels of Vehicle control treatment by 24 h. A the lower dose of 15 mg/kg, more than 50% suppression of Syk activity was observed between 2 and 6 h after oral administration o the compound.
• In Vitro:
  PRT062607 (P505-15) is a highly specific and potent inhibitor of purified Syk IC50 1-2 nM). In human whole blood, P505-15 potently inhibited 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). Similar levels of ex vivo Inhibition were measured after dosing in mice (Syk signaling IC50 0.32 μM). P505-15 abrogate the pro-survival effect of anti-IgM and induced CLL cell apoptosis. Treatment with P505-15 (2 mM mL) decreased CLL cell viability to 62.9 ± 5.1% after 48 hours. Treatment with lower concentration of PRT318 and P505-15 also reduce the viability of CLL cells.
• Cell Research:
  NLC co-cultures were established by suspending PBMC from patients with CLL in complete RPMI medium with 10% fetal bovine serum and penicillin-streptomycin-glutamine to a concentration of 107 cells mL (total 2 ml). Cells were incubated for 14 days in 24-well plates as previously described. To evaluate whethe the Syk inhibitors PRT318 and P505-15 could overcom the Protective effect of NLC, CLL cells were cultured under s andardized conditions on NLC or in suspension, in the presence or absence of PRT318 and P505-15. A the indicated time points, CLL cells were collected and assayed for cell viability as previously described.
• Animal Research:
  All animal studies were performed in strict accordance wit the Institutional Animal Care and Use Committee ethical guidelines. F Male BAL-/- mice received a Single oral dose of 15 or 30 mg/kg P505-15 and were anesthetized with a subcutaneous ketamine cocktail, and blood was 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 was dispensed into three heparin-containing tubes, one for determination of drug concentration an the remaining two for ex vivo stimulation with isotype control or anti-mouse IgD antibody for 10 min. Blood was processed for intracellular phospho-flow cytometry to evaluate BCR signaling as described earlier; mouse B cells were detected by using CD45R-B220 PerCP-conjugated antibody. Plasma Samples were analyzed for P505-15 concentration by using a liquid chromatography andem mass spectrometer the analytical range was 2 to 5000 ng/mL.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

FGR, Inhibitor, inhibit, P505-15 Hydrochloride, MLK1, P505-15, PRT 062607, PRT 062607 Hydrochloride, PRT062607, PRT-062607, PRT062607 (P505-15, BIIB057) HCl, PRT062607 hydrochloride, PRT062607 Hydrochloride, PRT-062607 hydrochloride, PRT-062607 Hydrochloride, Spleen tyrosine kinase, Syk

Compound Identifiers

PubChem CID

56948527