货号： C-7900-1 g 产品名称： Crizotinib, Free Base 品牌： LC 规格： 1 g
C-7900 Crizotinib, Free Base, >99% Synonyms: [PF-02341066] [PF-1066] [PF-2341066] Related Terms: [Xalkori] M.W. 450.34 C21H22Cl2FN5O [877399-52-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. Zou, H.Y., et al. “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms.” Cancer Res. 67: 4408-4417 (2007). •The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Yamazaki, S., et al. “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267-1274 (2008). •Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z., et al. “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296-306 (2010). •76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Bang, Y., et al. “Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). •Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE
C-7900 Crizotinib, Free Base, >99% Synonyms: [PF-02341066] [PF-1066] [PF-2341066] Related Terms: [Xalkori] M.W. 450.34 C21H22Cl2FN5O [877399-52-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. Zou, H.Y., et al. “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms.” Cancer Res. 67: 4408-4417 (2007). •The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Yamazaki, S., et al. “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267-1274 (2008). •Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z., et al. “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296-306 (2010). •76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Bang, Y., et al. “Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). •Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE
C-7900 Crizotinib, Free Base, >99% Synonyms: [PF-02341066] [PF-1066] [PF-2341066] Related Terms: [Xalkori] M.W. 450.34 C21H22Cl2FN5O [877399-52-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. Zou, H.Y., et al. “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms.” Cancer Res. 67: 4408-4417 (2007). •The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Yamazaki, S., et al. “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267-1274 (2008). •Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z., et al. “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296-306 (2010). •76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Bang, Y., et al. “Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). •Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE
C-7900 Crizotinib, Free Base, >99% Synonyms: [PF-02341066] [PF-1066] [PF-2341066] Related Terms: [Xalkori] M.W. 450.34 C21H22Cl2FN5O [877399-52-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. Zou, H.Y., et al. “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms.” Cancer Res. 67: 4408-4417 (2007). •The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Yamazaki, S., et al. “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267-1274 (2008). •Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z., et al. “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296-306 (2010). •76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Bang, Y., et al. “Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). •Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE
C-7900 Crizotinib, Free Base, >99% Synonyms: [PF-02341066] [PF-1066] [PF-2341066] Related Terms: [Xalkori] M.W. 450.34 C21H22Cl2FN5O [877399-52-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. Zou, H.Y., et al. “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms.” Cancer Res. 67: 4408-4417 (2007). •The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Yamazaki, S., et al. “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267-1274 (2008). •Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z., et al. “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296-306 (2010). •76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Bang, Y., et al. “Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). •Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE
C-7900 Crizotinib, Free Base, >99% Synonyms: [PF-02341066] [PF-1066] [PF-2341066] Related Terms: [Xalkori] M.W. 450.34 C21H22Cl2FN5O [877399-52-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. Zou, H.Y., et al. “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms.” Cancer Res. 67: 4408-4417 (2007). •The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Yamazaki, S., et al. “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267-1274 (2008). •Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z., et al. “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296-306 (2010). •76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Bang, Y., et al. “Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). •Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE
C-7900 Crizotinib, Free Base, >99% Synonyms: [PF-02341066] [PF-1066] [PF-2341066] Related Terms: [Xalkori] M.W. 450.34 C21H22Cl2FN5O [877399-52-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. Zou, H.Y., et al. “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms.” Cancer Res. 67: 4408-4417 (2007). •The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Yamazaki, S., et al. “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267-1274 (2008). •Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z., et al. “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296-306 (2010). •76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Bang, Y., et al. “Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). •Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE
C-7900 Crizotinib, Free Base, >99% Synonyms: [PF-02341066] [PF-1066] [PF-2341066] Related Terms: [Xalkori] M.W. 450.34 C21H22Cl2FN5O [877399-52-5] Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; soluble in ethanol at 25 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A •Crizotinib, also known as PF-02341066, is a potent ATP-competitive, recombinant human c-Met kinase inhibitor (Ki = 4 nM). In cell-based assays, it inhibited hepatocyte growth factor (HGF)-stimulated or constitutive total tyrosine phosphorylation of wild-type c-Met in a panel of human tumor and endothelial cell lines. It showed activity against c-Met phosphorylation in mIMCD3 mouse (IC50 = 5 nM) or MDCK canine (IC50 = 20 nM) epithelial cells. Crizotinib inhibited human GTL-16 gastric carcinoma cell growth (IC50 = 9.7 nM), induced apoptosis in GTL-16 cells (IC50 = 8.4 nM), inhibited HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion (IC50s of 11 and 6.1 nM, respectively), and inhibited MDCK cell scattering (IC50 = 16 nM). Crizotinib also inhibited HGF-stimulated c-Met phosphorylation (IC50 = 11 nM), cell survival (IC50 = 14 nM), and Matrigel invasion (IC50 = 35 nM) in human umbilical vascular endothelial cells. In addition, it inhibited serum-stimulated human dermal microvascular endothelial cell branching tubulogenesis (formation of vascular tubes) in fibrin gels. Crizotinib showed antitumor effects in vivo in c-Met-dependent human xenograft models including GTL-16 human gastric carcinoma, U87MG human glioblastoma, NCI-H441 NSCLC, Caki-1 RCC, and PC-3 prostate carcinoma. Zou, H.Y., et al. “An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms.” Cancer Res. 67: 4408-4417 (2007). •The EC90 (167 ng/ml) for the inhibition of cMet phosphorylation in athymic mice bearing GTL16 tumors corresponded to the EC50 (213 ng/ml) for the GTL16 tumor growth inhibition, indicating that near-complete inhibition of cMet phosphorylation (>90%) is required to significantly inhibit tumor growth (>50%). Yamazaki, S., et al. “Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available cMet kinase inhibitor in human tumor xenograft mouse models.” Drug Metab. Dispos. 36: 1267-1274 (2008). •Crizotinib showed gender-related differences in pharmacokinetics in rats, with at least 2-fold higher crizotinib plasma concentrations in males than females when administered at the same dose. In male rat liver S9 incubation oxidation was the major metabolic pathway, whereas in females sulfoconjugation predominanted. Zhong, W.Z., et al. “Gender specific drug metabolism of PF-02341066 in rats–role of sulfoconjugation.” Curr. Drug Metab. 11: 296-306 (2010). •76 patients with non-small cell lung cancer harboring anaplastic lymphoma kinase (ALK) fusion were recruited for a phase II clinical trial of crizotinib. The median half-life was about 53 hours. 50 patients were evaluable for response. The overall response rate was 64% and the disease control rate was 90%. Gastrointestinal toxicities (nausea and vomiting) were the most frequent adverse events. Bang, Y., et al. “Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC).” J. Clin. Oncol. 28: 3 (2010). •Crizotinib is the active ingredient in the drug sold under the trade name Xalkori®. This drug is currently approved in at least one country for use in patients with certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. NOTE: THE
Crizotinib Description A potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). Specifications Cas No. 877399-52-5 Product ID C6935 Product Name Crizotinib Formula Wt. 450.34 References Cui JJ, Tran-Dube M, Shen H, et al . J Med Chem. 54:6342-63 (2011). Okaniti W, Okamoto I, Arao T, et al. Mol Cancer Ther.11:1557-64 (2012).
Crizotinib Description A potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). Specifications Cas No. 877399-52-5 Product ID C6935 Product Name Crizotinib Formula Wt. 450.34 References Cui JJ, Tran-Dube M, Shen H, et al . J Med Chem. 54:6342-63 (2011). Okaniti W, Okamoto I, Arao T, et al. Mol Cancer Ther.11:1557-64 (2012).
Crizotinib Description A potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). Specifications Cas No. 877399-52-5 Product ID C6935 Product Name Crizotinib Formula Wt. 450.34 References Cui JJ, Tran-Dube M, Shen H, et al . J Med Chem. 54:6342-63 (2011). Okaniti W, Okamoto I, Arao T, et al. Mol Cancer Ther.11:1557-64 (2012).
Crizotinib Description A potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). Specifications Cas No. 877399-52-5 Product ID C6935 Product Name Crizotinib Formula Wt. 450.34 References Cui JJ, Tran-Dube M, Shen H, et al . J Med Chem. 54:6342-63 (2011). Okaniti W, Okamoto I, Arao T, et al. Mol Cancer Ther.11:1557-64 (2012).
Crizotinib A potent c-Met and ALK inhibitor Product Overview Product Name: Crizotinib Alternate Name/Synonyms: 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Description: A specific, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met and anaplastic lymphoma kinase (ALK). Iinhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations. Inhibits the growth and survival of cell lines dependent upon c-Met or ALK enzymatic activity. Peptide Sequence: N/A Appearance: Off-white solid Formulation: N/A CAS Number: 877399-52-5 Molecular Formula: C₂₁H₂₂Cl₂FN₅O Molecular Weight: 450.34 Purity: ≥98% by HPLC Solubility:DMSO Storage Temp.: -20°C Shipping Conditions: gel pack Handling: Protect from air and light SMILES: CC(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N InChi: InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1 InChi Key: KTEIFNKAUNYNJU-GFCCVEGCSA-N PubChem CID: 11626560 MDL Number: MFCD12407409 USAGE: For Research Use Only! Not For Use in Humans.
Crizotinib A potent c-Met and ALK inhibitor Product Overview Product Name: Crizotinib Alternate Name/Synonyms: 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Description: A specific, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met and anaplastic lymphoma kinase (ALK). Iinhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations. Inhibits the growth and survival of cell lines dependent upon c-Met or ALK enzymatic activity. Peptide Sequence: N/A Appearance: Off-white solid Formulation: N/A CAS Number: 877399-52-5 Molecular Formula: C₂₁H₂₂Cl₂FN₅O Molecular Weight: 450.34 Purity: ≥98% by HPLC Solubility:DMSO Storage Temp.: -20°C Shipping Conditions: gel pack Handling: Protect from air and light SMILES: CC(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N InChi: InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1 InChi Key: KTEIFNKAUNYNJU-GFCCVEGCSA-N PubChem CID: 11626560 MDL Number: MFCD12407409 USAGE: For Research Use Only! Not For Use in Humans.
