[3-[[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]oxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-yl]aMine
3-[1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine
CAS: 877399-52-5
Molecular Formula: C21H22Cl2FN5O
[3-[[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]oxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-yl]aMine - Names and Identifiers
[3-[[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]oxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-yl]aMine - Physico-chemical Properties
| Molecular Formula | C21H22Cl2FN5O |
| Molar Mass | 450.34 |
| Density | 1.47±0.1 g/cm3(Predicted) |
| Melting Point | 192 °C |
| Boling Point | 599.2±50.0 °C(Predicted) |
| Flash Point | 316.171°C |
| Solubility | Soluble in DMSO (25 mg/mL warming), ethanol (25 mg/mL warming), methanol, and chloroform |
| Vapor Presure | 0mmHg at 25°C |
| Appearance | powder |
| Color | white to tan |
| pKa | 9.81±0.10(Predicted) |
| Storage Condition | room temp |
| Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 2 months. |
| Refractive Index | 1.673 |
| Use | A Met inhibitor effective against various cell lines |
| In vitro study | PF-2341066 acted on mIMCD3 mouse and MDCK canine epithelial cells with similar effects on c-Met phosphorylation, with IC50 of 5 nM and 20 nM, respectively. PF-2341066 acted on NIH3T3 cells expressing c-Met ATP-binding site mutant V1092I or H1094R or P-loop mutant M1250T, with similar activity and increased activity, with IC50 of 19 nM, respectively, 2 nM and 15 nM, while the expression of the wild type receptor in NIH3T3 cells, IC50 was 13 nM. In contrast, it was observed that when PF-2341066 acted on cells expressing the c-Met activation loop mutants Y1230C and Y1235D, the effect was significantly changed compared to that of the wild-type receptor, with an IC50 of 127 nM and 92 nM, respectively. PF-2341066 acted on NCI-H69 and HOP92 cells expressing endogenous c-Met mutants R988C and T1010I, respectively, and also effectively inhibited c-Met phosphorylation, with IC50 of 13 nM and 16 nM, respectively. Compared with c-Met, PF-2341066 acts on VEGFR2 and pdgfrβrtks with more than 1000 times higher selectivity, IRK and Lck with more than 250 times higher selectivity, Tie2, TrkA, and TrkB are 40 to 60 times more selective. The selectivity for PF-2341066 acting on RON and Axl RTKs is 20 to 30 times. In contrast, PF-2341066 acts on ALK RTK-expressing nucleophossin (NPM)-anaplastic lymphoma kinase (ALK) The oncogenic fusion mutant and the KARPAS299 human anaplastic large cell lymphoma (ALCL) cell line had similar IC50 values of 24 nM. PF-2341066 inhibits the tumor phenotype of c-Met-dependent cancer cells, and the angiogenic phenotype of endothelial cells. PF-2341066 inhibit the growth of human GTL-16 gastric cancer cells with an IC50 of 9.7 nM. PF-2341066 induced apoptosis in GTL-16 cells with an IC50 of 8.4 nM. PF-2341066 inhibit HGF-stimulated human NCI-H441 lung cancer cell migration and invasion, the IC50 was 11 nM and 6.1 nM, respectively. PF-2341066 inhibition of MDCK cell scattering, IC50 16 nM. PF-2341066 inhibit HGF-stimulated c-Met phosphorylation, cell survival, and Matrigel invasion with IC50 of 11 nM, 14 nM, and 35 nM, respectively. In addition, PF-2341066 inhibits HMVEC branching tubule formation (formation of blood vessels) stimulated by serum in fibrin glue. PF-2341066 on Karpas299 or SU-DHL-1 ALCL cells, it also effectively inhibited NPM-ALK phosphorylation with an IC50 of 24 nM. PF-2341066 effectively inhibits cell proliferation, accompanied by stopping the cell cycle at G(1)-S phase, and induces apoptosis in ALK-positive ALCL cells with an IC50 of 30 nM, however, there was no effect on ALK-negative lymphoma cells. In addition, PF-2341066 inhibit some of the active behaviors of osteosarcoma, its tumor growth (e. G., proliferation and survival) and metastasis (e. G., invasion and formation of clones). |
| In vivo study | GTL-16 models were treated PF-2341066 50 mg/kg and 75 mg/kg daily, causing large tumors (the volume is larger than 600 mmPF-2341066 SCID Beige mice carrying Karpas299 ALCL transplanted tumors are orally treated at a dose of 100 mg/kg every day, which has high anti-cancer effect, and this effect is dose-dependent, after 15 days of treatment, all tumors completely declined. In addition, PF-2341066 inhibit key NPM-ALK signal regulators, including phospholipase C- gamma, signal transducer, and activator of transcription factor 3, extracellular signal-regulated kinase, and Akt, these are associated with inhibition of NPM-ALK phosphorylation and function. PF-2341066 inhibits some of the active behaviors of osteosarcoma, its tumor growth (e. G., proliferation and survival) and metastasis (e. G., invasion and formation of clones). Oral feeding of PF-2341066 to nude mice inhibits the growth and formation of bone matrix associated with osteosarcoma xenografts in nude mice. PF-2341066 treatment of c-MET-expanded GTL-16 xenografts at a dose of 50 mg/kg caused tumor regression, which was not in line with |
[3-[[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]oxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-yl]aMine - Risk and Safety
| Safety Description | 24/25 - Avoid contact with skin and eyes. |
| UN IDs | UN 3077 9 / PGIII |
| WGK Germany | 3 |
| HS Code | 29333990 |
| Hazard Class | IRRITANT |
[3-[[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]oxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-yl]aMine - Reference Information
| Overview | Crizotinib (Crizotinib,Xalkori R ), chemical name 3-[(R)-1-(2, 6-dichloro-3-fluorophenyl) ethoxy]-5- [1-(piperidin-4-yl)-1H-pyrazol-4-yl] pyridin-2-amine, white to light yellow powder. It is primarily used in the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) as determined by the SFDA-approved assay. |
| Use | crizotinib is a type of inhibitor against anaplastic lymphoma kinase (ALK), ROS1 and a small molecule tyrosine kinase inhibitor (TKI) of the other oncogene receptor tyrosine kinase MET. |
| indication | crizotinib capsules for anaplastic lymphoma kinase (ALK) as determined by SFDA approved assay treatment of patients with positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Approval for this indication is based primarily on evidence of objective response rate (ORR) and progression-free survival (PFS), with no evidence of survival benefit (OS) available. |
| non-small cell lung cancer treatment drug | crizotinib is a targeted therapy drug for non-small cell lung cancer developed by Pfizer, USA, secorri is a frontier and epoch-making drug in the field of targeted therapy for lung cancer. It was approved for marketing in the United States in August 2011 and was written into international lung cancer treatment guidelines at the end of the year as a first-line drug for ALK-positive patients. Co-approved with crizotinib is the first genetic diagnosis method using fluorescence in situ hybridization (FISH)-VSIs ALK Break Apart FISH Probe Kit, this is the method currently used in global clinical trials to detect EML4-ALK fusion genes in NSCLC. This test will help identify patients who may benefit from crizotinib treatment. on 25, this is the first drug to be used in the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as determined by an SFDA-approved assay. Sacre has opened a new chapter in the individualized treatment of lung cancer, enabling doctors to provide the right treatment for the right patient. In the serkerem clinical trial, the protocol required patients to test positive for the biomarker ALK fusion gene in their tumors to increase the likelihood of responding to treatment. This test, the first to be used for lung cancer treatment, allows researchers to observe good treatment effects in a pre-screened patient population. A study of 255 patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) in two multicenter, single-arm clinical trials (trial A and trial B) showed that, objective response rates were 51% and 61%, respectively. Preliminary Epidemiology studies have shown that ALK is approximately 3-5 percent positive in non-small cell lung cancer (NSCLC), meaning that there are approximately 28,000 to 46,000 ALK-positive NSCLC patients worldwide each year. Patient. The publication of ALK fusion gene results from non-small cell lung cancer (NSCLC) to FDA approval took only four years to develop the research and development, this is a major initiative in the field of oncology. This once again illustrates the importance of close cooperation between academic research, pharmaceutical, diagnostic and regulatory authorities. From the submission of a new drug application in China to the approval of SFDA today, the whole process took only about 11 months due to the inclusion of the rapid approval channel of the National Center for Drug Evaluation. crizotinib resistance is a major problem in the treatment of patients with ALK-positive non-small cell lung cancer. This resistance usually occurs within 1 year of treatment with crizotinib. Resistance in one third of the patients was caused by ALK tyrosine kinase gene mutation or ALK gene amplification. Ceritinib is a second-generation oral ALK tyrosine kinase inhibitor that does not act on the MET proto-oncogene but inhibits insulin-like growth factor 1 receptor. In preclinical models, ceritinib inhibited ALK 20-fold as effectively as crizotinib. The study found that ceritinib also responded to crizotinib-resistant central nervous system lesions NSCLC. Median progression-free survival with ceritinib for patients with NSCLC treated with crizotinib was 6.9 months, the median progression-free survival for patients not treated with crizotinib was 10.4 months. Preliminary Molecular analysis of some patients found that the resistance mechanism of Ceritinib is ALK-dependent or non-ALK-dependent, it has clinical benefit for most patients. This finding suggests that ceritinib can effectively inhibit the ALK target, which may act on an unknown but drug resistance-related kinase, and thus the drug resistance of Crizotinib can be overcome. |
| biological activity | Crizotinib (PF-02341066) Crizotinib is a potent c-Met and ALK inhibitor, the IC50 values in the cell assay were 11 nM and 24 nM, respectively. It is also a potent inhibitor of ROS1 with a Ki value of less than 0.025 nM. Crizotinib can induce autophagy in a variety of lung cancer cell lines by inhibiting the STAT3 pathway. |
| Target | Value |
| ROS1 (Cell-free assay) | <0.025 nM(Ki) |
| c-Met (A549, MDA-MB-231, GTL-16, HT29, 786-O, Colo-205, A498 cells) | 11 nM |
| ALK (Karpas299 cells) | 24 nM |
Last Update：2024-04-10 22:29:15
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Product Name: Crizotinib Visit Supplier Webpage Request for quotationCAS: 877399-52-5
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Spot supply
Product Name: Crizotinib Visit Supplier Webpage Request for quotationCAS: 877399-52-5
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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