SML1693

Pz-1

≥98% (HPLC)

• Synonym(s): N-(5-(Tert-Butyl)isoxazol-3-yl)-2-(4-(5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)phenyl)acetamide
• Empirical Formula (Hill Notation): C₂₆H₂₆N₆O₂
• CAS Number: 1800505-64-9
• Molecular Weight: 454.52
• UNSPSC Code: 12352200
• PubChem Substance ID: 329826021
• NACRES: NA.77
• Assay: ≥98% (HPLC)
• Form: powder
• Quality level: 100

Properties

• InChI: 1S/C26H26N6O2/c1-26(2,3)23-13-24(30-34-23)29-25(33)11-17-5-8-20(9-6-17)32-16-27-21-12-18(7-10-22(21)32)19-14-28-31(4)15-19/h5-10,12-16H,11H2,1-4H3,(H,29,30,33)
• InChI key: NJLMIILZNLZZFW-UHFFFAOYSA-N
• SMILES string: CN1N=CC(C(C=C2)=CC3=C2N(C4=CC=C(CC(NC5=NOC(C(C)(C)C)=C5)=O)C=C4)C=N3)=C1
• assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 1 mg/mL, clear (warmed)
• storage temp.: 2-8°C
• Quality Level: 100

Description

Biochem/physiol Actions

Pz-1 is a cell-permeable, non-cytotoxic (up to 0.1 μM and 6 days; NIH/3T3 cells), and highly potent type II kinase inhibitor that potently inhibits RET and VEGFR2 tyrosine kinase activity (IC₅₀ <1 nM; [ATP] = 190 μM) by targeting the kinases in their inactive DFG-out conformation, displaying significant affinity (Kd <50 nM) toward only TRKB, TRKC, GKA, FYN, SRC, TAK1, MUSK from a panel of 96 other kinases. Pz-1 inhibits cellular RET mutants (C634R, C634Y, V804L, V804M, M918T) and VEGFR2 phosphorylations, and selectively inhibits the growth of RET C634Y- than HRas G12V-transformed NIH/3T3 cultures (IC₅₀ = 0.5 vs. 34.4 nM). Likewise, Pz-1 completely abrogated tumor formation from RET C634Y-transformed NIH/3T3 cells in mice in vivo (1 mg/kg/d, p.o.), while only up to 70% tumor suppression of HRas G12V-transformed cells was achieved with 10 mg/kg daily oral dosage.

Pz-1 is a cell-permeable, non-cytotoxic and highly potent type II kinase inhibitor that potently inhibits RET and VEGFR2 tyrosine kinase activity.

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable