1800505-64-9
1800505-64-9 structure
- Name: Pz-1
- Chemical Name: Pz-1
- CAS Number: 1800505-64-9
- Molecular Formula: C26H26N6O2
- Molecular Weight: 454.52
- Catalog: Research Areas Cancer
- Create Date: 2018-05-26 21:13:49
- Modify Date: 2024-01-16 18:20:10
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Pz-1 is a potent RET and VEGFR2 inhibitor with IC50s of less than 1 nM for both wild type kinases.
| Name | Pz-1 |
|---|
| Description | Pz-1 is a potent RET and VEGFR2 inhibitor with IC50s of less than 1 nM for both wild type kinases. |
|---|---|
| Related Catalog | |
| Target |
IC50: < 1 nM (RET and VEGFR2)[1] |
| In Vitro | Pz-1 is a Type-II tyrosine kinase inhibitor, able to bind the DFG-out conformation of the kinase. In cell-based assays, 1.0 nM of Pz-1 strongly inhibits tyrosine phosphorylation of VEGFR2 and clinically relevant RET mutants, including those refractory to vandetanib and cabozantinib (RETV804M and RETV804L)[1]. |
| In Vivo | Pz-1 is shown active on VEGFR2, which can block blood supply required for RET-stimulated growth. At 1.0 mg/kg/day per os, Pz-1 abrogates formation of tumors induced by RET-mutant fibroblasts and blocks phosphorylation of both RET and VEGFR2 in tumor tissue. Pz-1 features no detectable toxicity up to 100.0 mg/kg, which indicates a large therapeutic window[1]. |
| Animal Admin | Mice[1] In order to address in vivo RET-driven effects, Pz-1 is tested on tumors induced by oncogenic RET compared to a constitutively-active control Ras oncogene. Immunodeficient (nu/nu) mice are then injected with NIH3T3 RETC634Y or NIH3T3 HRasG12V cells and, before tumors have appeared, treated PO with Pz-1 (1.0, 3.0 or 10.0 mg/kg/day) or left untreated. Then the tumor effects are measured[1] |
| References |
| Molecular Formula | C26H26N6O2 |
|---|---|
| Molecular Weight | 454.52 |