product name PF-06463922
Description: PF-06463922, also known as loratinib, is a potent, orally available, ATP-competitive, and dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 has demonstrated potential antineoplastic activity. Upon administration, PF-06463922 binds to and inhibits both ALK and ROS1 kinases which leads to disruption of ALK- and ROS1-mediated signaling and eventually inhibition of tumor cell growth.
References: J Med Chem. 2014 Jun 12;57(11):4720-44; Clin Cancer Res. 2012 Sep 1;18(17):4570-9.
406.41
Formula
C21H19FN6O2
CAS No.
1454846-35-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 81 mg/mL (199.3 mM)
Water: <1 mg/mL
Ethanol: 30 mg/mL warmed (73.8 mM)
Solubility (In vivo)
Synonyms
Loratinib
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19399400
| In Vitro |
In vitro activity: PF-06463922 demonstrates significant cell activity against ALK and a large set of ALK clinical mutations with IC50 ranging from 0.2 nM-77 nM. PF-06463922 significantly inhibits cell proliferation and induces cell apoptosis in the HCC78 human NSCLC cells harboring SLC34A2-ROS1 fusions and the BaF3-CD74-ROS1 cells expressing human CD74-ROS1. PF-06463922 also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In rats, PF-06463922 displays low plasma clearance, a moderate volume of distribution, a reasonable half-life, low propensity for p-glycoprotein 1-mediated efflux and a bioavailability of 100%. In vivo, PF-06463922 shows cytoreductive antitumor efficacy in the NIH3T3 xenograft models expressing human CD74-ROS1 and Fig-ROS1 via inhibition in ROS1 phosphorylation and the downstream signaling molecules, as well as inhibition of the cell cycle protein Cyclin D1 in tumors. In vivo, PF-06463922 also demonstrates marked antitumor activity in mice bearing tumor xenografts expressing EML4-ALK, EML4-ALK-L1196M, EML4-ALK-G1269A, EML4-ALK-G1202R or NPM-ALK. |
| Animal model | |
| Formulation & Dosage | |
| References | J Med Chem. 2014 Jun 12;57(11):4720-44; Clin Cancer Res. 2012 Sep 1;18(17):4570-9. |
Related Posts
product name PF-06463922
Description: PF-06463922, also known as loratinib, is a potent, orally available, ATP-competitive, and dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 has demonstrated potential antineoplastic activity. Upon administration, PF-06463922 binds to and inhibits both ALK and ROS1 kinases which leads to disruption of ALK- and ROS1-mediated signaling and eventually inhibition of tumor cell growth.
References: J Med Chem. 2014 Jun 12;57(11):4720-44; Clin Cancer Res. 2012 Sep 1;18(17):4570-9.
406.41
Formula
C21H19FN6O2
CAS No.
1454846-35-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 81 mg/mL (199.3 mM)
Water: <1 mg/mL
Ethanol: 30 mg/mL warmed (73.8 mM)
Solubility (In vivo)
Synonyms
Loratinib
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19399400
| In Vitro |
In vitro activity: PF-06463922 demonstrates significant cell activity against ALK and a large set of ALK clinical mutations with IC50 ranging from 0.2 nM-77 nM. PF-06463922 significantly inhibits cell proliferation and induces cell apoptosis in the HCC78 human NSCLC cells harboring SLC34A2-ROS1 fusions and the BaF3-CD74-ROS1 cells expressing human CD74-ROS1. PF-06463922 also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In rats, PF-06463922 displays low plasma clearance, a moderate volume of distribution, a reasonable half-life, low propensity for p-glycoprotein 1-mediated efflux and a bioavailability of 100%. In vivo, PF-06463922 shows cytoreductive antitumor efficacy in the NIH3T3 xenograft models expressing human CD74-ROS1 and Fig-ROS1 via inhibition in ROS1 phosphorylation and the downstream signaling molecules, as well as inhibition of the cell cycle protein Cyclin D1 in tumors. In vivo, PF-06463922 also demonstrates marked antitumor activity in mice bearing tumor xenografts expressing EML4-ALK, EML4-ALK-L1196M, EML4-ALK-G1269A, EML4-ALK-G1202R or NPM-ALK. |
| Animal model | |
| Formulation & Dosage | |
| References | J Med Chem. 2014 Jun 12;57(11):4720-44; Clin Cancer Res. 2012 Sep 1;18(17):4570-9. |