VS 8 (Compound VS 8) 是一种有效的口服 VEGFR-2 抑制剂，具有显著的抗血管生成 (anti-angiogenic) 作用。 VS 8 诱导癌细胞凋亡 (apoptosis) 和迁移。 VS 8 对 CSCs (癌症干细胞)有活性。
VS 8 Chemical Structure
CAS No. : 2471865-38-8
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
VS 8 (Compound VS 8) is a potent, orally active VEGFR-2 inhibitor with significant anti-angiogenic effects. VS 8 induces cancer cell apoptosis and migration. VS 8 is active against CSCs (Cancer stem cells)[1].
IC50 & Target
VEGFR-2
体外研究 (In Vitro)
VS 8 (Compound VS 8) (0.01-100 µM, 24 h) shows potent anti-proliferative activity against MCF-7, MDA-MB-231, Hep G2, and HUVECs cells[1]. VS 8 induces early apoptosis in MDA-MB-231 (1413 nM, 72 h), Hep G2 (257.80 nM, 24 h), and HUVECs (1954 nM, 24 h) cells[1]. VS 8 is shown to be a pro-oxidant molecule that enhances the ROS level in Hep G2 cells[1]. VS 8 inhibits wound healing and migration of MCF-7 cancer cells[1]. VS 8 downregulates human vascular endothelial growth factor (hVEGF) and hVEGFR-2 expression in HUVECs[1]. VS 8 (257.80 nM, 48 h) arrests cell cycle at ‘G0/G1’ and ‘S’ phase in CD44+ and CD133+ CSCs, respectively[1]. VS 8 inhibits TGF-β-induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma by the upregulation of E-cadherin and the suppression of vimentin and SNAIL[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
Cell Line:
MCF-7, MDA-MB-231, Hep G2, and HUVECs cells
Concentration:
0.01, 0.1, 1, 10, 50, and 100 µM
Incubation Time:
24 h
Result:
Showed significantly potent anti-proliferative activity against all the selected cell lines in a dose-dependent manner, with IC50 values of 953.30, 1413, 257.80, and 1954 nM against MCF-7, MDA-MB-231, Hep G2, and HUVECs cells.
Apoptosis Analysis[1]
Cell Line:
MDA-MB-231, Hep G2, and HUVECs cells
Concentration:
1413, 257.80, and 1954 nM for MDA-MB-231, Hep G2, and HUVECs cells, respectively.
Incubation Time:
72 h for MDA-MB-231 cells; 24 h for Hep G2 and HUVECs cells
Result:
Resulted in high population of early apoptotic MDA-MB-231 cells (68.34 ± 0.18%). A significant increase in % apoptotic index (~86.66%) was observed in Hep G2 cells. The percentage of early apoptotic cells were found to be ~37.53% in HUVECs cells.
Cell Cycle Analysis[1]
Cell Line:
CD44+ and CD133+ CSCs isolated from Hep G2 cells
Concentration:
257.80 nM
Incubation Time:
48 h
Result:
Arrested cell cycle at ‘G0/G1’ and ‘S’ phase in CD44+ and CD133+ CSCs, respectively.
体内研究 (In Vivo)
VS 8 inhibits angiogenesis in the chick chorioallantoic membrane without oral toxicity[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male Wistar rats (180-220 gm)[1]
Dosage:
5 mg/kg
Administration:
Oral administration (Pharmacokinetic Analysis)
Result:
Pharmacokinetic parameters for VS 8 in rats after administration of oral dose (5 mg/ kg) [1]
Pharmacokinetic parameters
Unit
Value
Cmax
μg/mL
39.7193 ± 0.36
Tmax
hrs
6 ± 0
AUC(0-72)
mg/mL*hrs
621.3236 ± 1.843
AUC(0-∞)
mg/mL*hrs
625.2219 ± 1.864
AUMC(0-∞)
(mg/mL*hrs2)
8929.284 ± 72.85
MRT
hrs
14.2817 ± 0.102
t1/2
hrs
11.9277 ± 0.324
Data represented as mean ± SD (n = 3); t1/2, Half-Life; Cmax, Maximum Observed Concentration; Tmax, Maximum Observed Time; AUC, Area Under Curve; AUMC Area Under Movement Curve, MRT, Mean Residence Time.
分子量
479.45
Formula
C26H20F3N3O3
CAS 号
2471865-38-8
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Siddharth J Modi, et al. Discovery of VEGFR-2 inhibitors exerting significant anticancer activity against CD44+ and CD133+ cancer stem cells (CSCs): Reversal of TGF-β induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma. Eur J Med Chem. 2020 Dec 1;207:112851.
VS 8 (Compound VS 8) 是一种有效的口服 VEGFR-2 抑制剂，具有显著的抗血管生成 (anti-angiogenic) 作用。 VS 8 诱导癌细胞凋亡 (apoptosis) 和迁移。 VS 8 对 CSCs (癌症干细胞)有活性。
VS 8 Chemical Structure
CAS No. : 2471865-38-8
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
VS 8 (Compound VS 8) is a potent, orally active VEGFR-2 inhibitor with significant anti-angiogenic effects. VS 8 induces cancer cell apoptosis and migration. VS 8 is active against CSCs (Cancer stem cells)[1].
IC50 & Target
VEGFR-2
体外研究 (In Vitro)
VS 8 (Compound VS 8) (0.01-100 µM, 24 h) shows potent anti-proliferative activity against MCF-7, MDA-MB-231, Hep G2, and HUVECs cells[1]. VS 8 induces early apoptosis in MDA-MB-231 (1413 nM, 72 h), Hep G2 (257.80 nM, 24 h), and HUVECs (1954 nM, 24 h) cells[1]. VS 8 is shown to be a pro-oxidant molecule that enhances the ROS level in Hep G2 cells[1]. VS 8 inhibits wound healing and migration of MCF-7 cancer cells[1]. VS 8 downregulates human vascular endothelial growth factor (hVEGF) and hVEGFR-2 expression in HUVECs[1]. VS 8 (257.80 nM, 48 h) arrests cell cycle at ‘G0/G1’ and ‘S’ phase in CD44+ and CD133+ CSCs, respectively[1]. VS 8 inhibits TGF-β-induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma by the upregulation of E-cadherin and the suppression of vimentin and SNAIL[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
Cell Line:
MCF-7, MDA-MB-231, Hep G2, and HUVECs cells
Concentration:
0.01, 0.1, 1, 10, 50, and 100 µM
Incubation Time:
24 h
Result:
Showed significantly potent anti-proliferative activity against all the selected cell lines in a dose-dependent manner, with IC50 values of 953.30, 1413, 257.80, and 1954 nM against MCF-7, MDA-MB-231, Hep G2, and HUVECs cells.
Apoptosis Analysis[1]
Cell Line:
MDA-MB-231, Hep G2, and HUVECs cells
Concentration:
1413, 257.80, and 1954 nM for MDA-MB-231, Hep G2, and HUVECs cells, respectively.
Incubation Time:
72 h for MDA-MB-231 cells; 24 h for Hep G2 and HUVECs cells
Result:
Resulted in high population of early apoptotic MDA-MB-231 cells (68.34 ± 0.18%). A significant increase in % apoptotic index (~86.66%) was observed in Hep G2 cells. The percentage of early apoptotic cells were found to be ~37.53% in HUVECs cells.
Cell Cycle Analysis[1]
Cell Line:
CD44+ and CD133+ CSCs isolated from Hep G2 cells
Concentration:
257.80 nM
Incubation Time:
48 h
Result:
Arrested cell cycle at ‘G0/G1’ and ‘S’ phase in CD44+ and CD133+ CSCs, respectively.
体内研究 (In Vivo)
VS 8 inhibits angiogenesis in the chick chorioallantoic membrane without oral toxicity[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male Wistar rats (180-220 gm)[1]
Dosage:
5 mg/kg
Administration:
Oral administration (Pharmacokinetic Analysis)
Result:
Pharmacokinetic parameters for VS 8 in rats after administration of oral dose (5 mg/ kg) [1]
Pharmacokinetic parameters
Unit
Value
Cmax
μg/mL
39.7193 ± 0.36
Tmax
hrs
6 ± 0
AUC(0-72)
mg/mL*hrs
621.3236 ± 1.843
AUC(0-∞)
mg/mL*hrs
625.2219 ± 1.864
AUMC(0-∞)
(mg/mL*hrs2)
8929.284 ± 72.85
MRT
hrs
14.2817 ± 0.102
t1/2
hrs
11.9277 ± 0.324
Data represented as mean ± SD (n = 3); t1/2, Half-Life; Cmax, Maximum Observed Concentration; Tmax, Maximum Observed Time; AUC, Area Under Curve; AUMC Area Under Movement Curve, MRT, Mean Residence Time.
分子量
479.45
Formula
C26H20F3N3O3
CAS 号
2471865-38-8
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Siddharth J Modi, et al. Discovery of VEGFR-2 inhibitors exerting significant anticancer activity against CD44+ and CD133+ cancer stem cells (CSCs): Reversal of TGF-β induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma. Eur J Med Chem. 2020 Dec 1;207:112851.
VS 8 (Compound VS 8) 是一种有效的口服 VEGFR-2 抑制剂，具有显著的抗血管生成 (anti-angiogenic) 作用。 VS 8 诱导癌细胞凋亡 (apoptosis) 和迁移。 VS 8 对 CSCs (癌症干细胞)有活性。
VS 8 Chemical Structure
CAS No. : 2471865-38-8
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
VS 8 (Compound VS 8) is a potent, orally active VEGFR-2 inhibitor with significant anti-angiogenic effects. VS 8 induces cancer cell apoptosis and migration. VS 8 is active against CSCs (Cancer stem cells)[1].
IC50 & Target
VEGFR-2
体外研究 (In Vitro)
VS 8 (Compound VS 8) (0.01-100 µM, 24 h) shows potent anti-proliferative activity against MCF-7, MDA-MB-231, Hep G2, and HUVECs cells[1]. VS 8 induces early apoptosis in MDA-MB-231 (1413 nM, 72 h), Hep G2 (257.80 nM, 24 h), and HUVECs (1954 nM, 24 h) cells[1]. VS 8 is shown to be a pro-oxidant molecule that enhances the ROS level in Hep G2 cells[1]. VS 8 inhibits wound healing and migration of MCF-7 cancer cells[1]. VS 8 downregulates human vascular endothelial growth factor (hVEGF) and hVEGFR-2 expression in HUVECs[1]. VS 8 (257.80 nM, 48 h) arrests cell cycle at ‘G0/G1’ and ‘S’ phase in CD44+ and CD133+ CSCs, respectively[1]. VS 8 inhibits TGF-β-induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma by the upregulation of E-cadherin and the suppression of vimentin and SNAIL[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
Cell Line:
MCF-7, MDA-MB-231, Hep G2, and HUVECs cells
Concentration:
0.01, 0.1, 1, 10, 50, and 100 µM
Incubation Time:
24 h
Result:
Showed significantly potent anti-proliferative activity against all the selected cell lines in a dose-dependent manner, with IC50 values of 953.30, 1413, 257.80, and 1954 nM against MCF-7, MDA-MB-231, Hep G2, and HUVECs cells.
Apoptosis Analysis[1]
Cell Line:
MDA-MB-231, Hep G2, and HUVECs cells
Concentration:
1413, 257.80, and 1954 nM for MDA-MB-231, Hep G2, and HUVECs cells, respectively.
Incubation Time:
72 h for MDA-MB-231 cells; 24 h for Hep G2 and HUVECs cells
Result:
Resulted in high population of early apoptotic MDA-MB-231 cells (68.34 ± 0.18%). A significant increase in % apoptotic index (~86.66%) was observed in Hep G2 cells. The percentage of early apoptotic cells were found to be ~37.53% in HUVECs cells.
Cell Cycle Analysis[1]
Cell Line:
CD44+ and CD133+ CSCs isolated from Hep G2 cells
Concentration:
257.80 nM
Incubation Time:
48 h
Result:
Arrested cell cycle at ‘G0/G1’ and ‘S’ phase in CD44+ and CD133+ CSCs, respectively.
体内研究 (In Vivo)
VS 8 inhibits angiogenesis in the chick chorioallantoic membrane without oral toxicity[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male Wistar rats (180-220 gm)[1]
Dosage:
5 mg/kg
Administration:
Oral administration (Pharmacokinetic Analysis)
Result:
Pharmacokinetic parameters for VS 8 in rats after administration of oral dose (5 mg/ kg) [1]
Pharmacokinetic parameters
Unit
Value
Cmax
μg/mL
39.7193 ± 0.36
Tmax
hrs
6 ± 0
AUC(0-72)
mg/mL*hrs
621.3236 ± 1.843
AUC(0-∞)
mg/mL*hrs
625.2219 ± 1.864
AUMC(0-∞)
(mg/mL*hrs2)
8929.284 ± 72.85
MRT
hrs
14.2817 ± 0.102
t1/2
hrs
11.9277 ± 0.324
Data represented as mean ± SD (n = 3); t1/2, Half-Life; Cmax, Maximum Observed Concentration; Tmax, Maximum Observed Time; AUC, Area Under Curve; AUMC Area Under Movement Curve, MRT, Mean Residence Time.
分子量
479.45
Formula
C26H20F3N3O3
CAS 号
2471865-38-8
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Siddharth J Modi, et al. Discovery of VEGFR-2 inhibitors exerting significant anticancer activity against CD44+ and CD133+ cancer stem cells (CSCs): Reversal of TGF-β induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma. Eur J Med Chem. 2020 Dec 1;207:112851.
Defactinib (VS-6063; PF-04554878) is a novel FAK inhibitor with potential antiangiogenic and antineoplastic activities.
IC50 & Target
FAK[1]
体外研究 (In Vitro)
Defactinib (VS-6063) inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. RPPA data shows that Defactinib reduces levels of AKT and YB-1 in taxane-resistant cell lines. The expression of pFAK (Tyr397) is statistically significantly inhibited by Defactinib in a dose-dependent manner in all cell lines. Defactinib inhibits pFAK (Tyr397) expression within 3 hours, with a gradual return of expression by 48 hours[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Defactinib (VS-6063) doses of 25 mg/kg twice a day or greater statistically significantly inhibits pFAK (Tyr397) at 3 hours, with return of expression noted by 24 hours. Therefore, administration of Defactinib at 25 mg/kg twice a day is selected as the dosing schedule for subsequent therapy experiments. For therapy experiments, female nude mice bearing HeyA8 tumors in the peritoneal cavity are randomly divided into 4 groups (n=10 per group): 1) vehicle orally twice daily and phosphate-buffered saline intraperitoneally weekly (control); 2) Defactinib 25 mg/kg orally twice daily; 3) PTX intraperitoneally weekly; and 4) both VDefactinib 25 mg/kg orally twice daily and PTX intraperitoneally weekly. There is an 87.4% reduction in tumor weight by PTX monotherapy in the HeyA8 model, and combination therapy resulted in the greatest tumor weight reduction, with a 97.9% reduction (P=0.05 compared with PTX). In the SKOV3ip1 model, a 92.7% tumor weight reduction is observed in the combination group compared with PTX (P<0.001)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
510.49
Formula
C20H21F3N8O3S
CAS 号
1073154-85-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 50 mg/mL (97.95 mM; Need ultrasonic)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
[1]. Kang Y, et al. Role of focal adhesion kinase in regulating YB-1-mediated resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95.
Animal Administration [1]
Mice[1] To determine the antitumor effects of Defactinib, SKOV3ip1, SKOV3-TR, HeyA8, and HeyA8-MDR cells are injected intraperitoneally. One week after tumor cell injection, mice are randomly assigned to 4 groups of 10 mice (control, PTX alone, Defactinib alone, and PTX with Defactinib); treatment is initiated at 3-4 weeks following injection. PTX at 2 mg/kg (SKOV3ip1 and SKOV3-TR) or 2.5 mg/kg (HeyA8 and HeyA8-MDR) is given intraperitoneally weekly; Defactinib at 25 mg/kg is given orally twice every day. Control mice received HBSS intraperitoneally once a week and vehicle orally twice every day. Mice are monitored daily for adverse effects of therapy and are killed on day 35 (SKOV3ip1 or SKOV3-TR), day 28 (HeyA8 or HeyA8-MDR), or when any of the mice seemed moribund. Total body weight, tumor incidence and mass, and the number of tumor nodules are recorded. Tumors are either fixed in formalin or embedded in paraffin or snap frozen in optimal cutting temperature (OCT) compound in liquid nitrogen.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Kang Y, et al. Role of focal adhesion kinase in regulating YB-1-mediated resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95.
Defactinib hydrochloride (VS-6063 hydrochloride; PF 04554878 hydrochloride) is a novel FAK inhibitor, which inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner.
IC50 & Target
FAK[1]
体外研究 (In Vitro)
Defactinib (VS-6063) inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner. RPPA data shows that Defactinib reduces levels of AKT and YB-1 in taxane-resistant cell lines. The expression of pFAK (Tyr397) is statistically significantly inhibited by Defactinib in a dose-dependent manner in all cell lines. Defactinib inhibits pFAK (Tyr397) expression within 3 hours, with a gradual return of expression by 48 hours[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Defactinib (VS-6063) doses of 25 mg/kg twice a day or greater statistically significantly inhibits pFAK (Tyr397) at 3 hours, with return of expression noted by 24 hours. Therefore, administration of Defactinib at 25 mg/kg twice a day is selected as the dosing schedule for subsequent therapy experiments. For therapy experiments, female nude mice bearing HeyA8 tumors in the peritoneal cavity are randomly divided into 4 groups (n=10 per group): 1) vehicle orally twice daily and phosphate-buffered saline intraperitoneally weekly (control); 2) Defactinib 25 mg/kg orally twice daily; 3) PTX intraperitoneally weekly; and 4) both VDefactinib 25 mg/kg orally twice daily and PTX intraperitoneally weekly. There is an 87.4% reduction in tumor weight by PTX monotherapy in the HeyA8 model, and combination therapy resulted in the greatest tumor weight reduction, with a 97.9% reduction (P=0.05 compared with PTX). In the SKOV3ip1 model, a 92.7% tumor weight reduction is observed in the combination group compared with PTX (P<0.001)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
546.95
Formula
C20H22ClF3N8O3S
CAS 号
1073160-26-5
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Kang Y, et al. Role of focal adhesion kinase in regulating YB-1-mediated resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95.
Animal Administration [1]
Mice[1] To determine the antitumor effects of Defactinib, SKOV3ip1, SKOV3-TR, HeyA8, and HeyA8-MDR cells are injected intraperitoneally. One week after tumor cell injection, mice are randomly assigned to 4 groups of 10 mice (control, PTX alone, Defactinib alone, and PTX with Defactinib); treatment is initiated at 3-4 weeks following injection. PTX at 2 mg/kg (SKOV3ip1 and SKOV3-TR) or 2.5 mg/kg (HeyA8 and HeyA8-MDR) is given intraperitoneally weekly; Defactinib at 25 mg/kg is given orally twice every day. Control mice received HBSS intraperitoneally once a week and vehicle orally twice every day. Mice are monitored daily for adverse effects of therapy and are killed on day 35 (SKOV3ip1 or SKOV3-TR), day 28 (HeyA8 or HeyA8-MDR), or when any of the mice seemed moribund. Total body weight, tumor incidence and mass, and the number of tumor nodules are recorded. Tumors are either fixed in formalin or embedded in paraffin or snap frozen in optimal cutting temperature (OCT) compound in liquid nitrogen.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Kang Y, et al. Role of focal adhesion kinase in regulating YB-1-mediated resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95.
VS-5584 is a pan-PI3K/mTOR kinase inhibitor with IC50s of 16 nM, 68 nM, 42 nM, 25 nM, and 37 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively. VS-5584 simultaneously blocks mTORC2 as well as mTORC1.
IC50 & Target[1]
PI3Kα
16 nM (IC50)
PI3Kγ
25 nM (IC50)
PI3Kδ
42 nM (IC50)
PI3Kβ
68 nM (IC50)
Vps34
7470 nM (IC50)
mTOR
37 nM (IC50)
mTORC1
mTORC2
DNA-PK
1270 nM (IC50)
体外研究 (In Vitro)
VS-5584 is an ATP-competitive inhibitor which selectively inhibits PI3K/mTOR signaling with equivalent low nanomolar potency against all human Class I PI3K isoforms and mTOR kinase. VS-5584 (0.001, 0.01, 0.1,1,10 and 100 μM) preferentially inhibits cancer stem cells in HMLE breast cancer cells while Paclitaxel increases the percentage of cancer stem cells. VS-5584 (0.1, 1, 10, 100 and 1000 nM) reduces the number of Aldefluor-positive cancer stem cells while Paclitaxel increases the percentage of cancer stem cells. VS-5584 (10, 30, 100, 300 nM) reduces the percentage of cancer stem cells (side population) in a Hoechst dye exclusion assay[1]. VS-5584 is a potent inhibitor of mTOR (IC50=37 nM) as well as class I PI3K isoforms (IC50: PI3Kα=16 nM; PI3Kβ=68 nM; PI3Kγ=25 nM; PI3Kδ=42 nM). All other evaluated kinases show negligible binding when tested up to 10 μM VS-5584[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Nude mice bearing MDA-MB-231 human breast cancer tumors are treated for 5 days with once daily oral VS-5584 (25 mg/kg). Oral treatment of tumor bearing mice with VS-5584 reduces cancer atem cells analyzed from extracted tumors. Mice are implanted with tumor fragments from a docetaxel-resistant patient-derived triple negative breast cancer. Mice are treated with VS-5584 (20 mg/kg, po, qd) or Docetaxel (20 mg/kg, i.v.). Oral VS-5584 induces tumor regression in a Docetaxel-resistant patient-derived breast cancer model[1]. A single oral dose of VS-5584 is rapidly absorbed with a tmax of 0.9 hours and an elimination half-life of 10 hours. To determine the pharmacokinetic and pharmacodynamic relationship in tumors, PC3-tumor–bearing mice are treated with a single dose of VS-5584 and plasma and tumors are harvested after 6 hours and analyzed for concentrations of VS-5584 and effects on target efficacy biomarkers. Plasma levels of VS-5584 increase dose-dependently. For evaluation of efficacy in a Rapamycin-sensitive PC3 engraftment model, tumor-bearing mice are treated with VS-5584 for 28 days in comparison with the rapalog Everolimus. VS-5584 is well tolerated at both doses tested (11 and 25 mg/kg) with minimal weight loss (mean 4.7% on day 27). Treatment with VS-5584 leads to significant tumor growth inhibition (TGI) of 79% and 113% for 11 and 25 mg/kg, respectively[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
354.41
Formula
C17H22N8O
CAS 号
1246560-33-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Hart S, et al. VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther, 2013, 12(2), 151-161.
Cell Assay [1]
For proliferation assays in 96-well plates, SET-2, SNU-478, SNU-1196, SNU-245, SNU-1079, SNU-308, SNU-869, and MKN7 cells are used. The multiple myeloma cells (H929, MM1.S, MM1.R, R8226, U266) and nasopharyngeal cells (CNE-1, CNE-2, HONE1, HK1) are used. Cells are seeded at 30% to 50% confluency for adherent cells, or 2,000 to 6,000 cells for suspension cells and treated the following day with VS-5584 (in triplicates) at concentrations up to 10 μM for 48 hours. Cell viability is monitored using the CellTiter-Glo assay. Dose-response curves were plotted to determine IC50 values for the compounds using the XL-fit software[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] Athymic BALB/c nude mice (BALB/cOlaHsd-Foxn1nu) are used. Fox-Chase severe combined immunodeficient (SCID) mice (CB17/Icr-Prkdcscid/CrlBltw) are used. Male (PC3 and COLO 205) or female (MV4-11 and HuH7) BALB/c nude mice or female SCID mice (NCI-N87) are implanted intradermally in the right flank with 5×106 (PC3, COLO205, HuH7, NCI-N87) or 1×107 (MV4-11) cells. Cells are resuspended in 70% (v/v; COLO205 and HuH7 only) or 50% (v/v) serum-free growth medium/Matrigel and injected in a total volume of 100 μL, using a 27.5-gauge needle. Dosing started 7 to 14 days after tumor implantation. VS-5584 (11 and 25 mg/kg) is dosed daily orally[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Hart S, et al. VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther, 2013, 12(2), 151-161.
PND-1186 (VS-4718) is a potent, highly-specific and reversible inhibitor of FAK with an IC50 of 1.5 nM. PND-1186 selectively promotes tumor cell apoptosis[1].
IC50 & Target
IC50: 1.5 nM (FAK)[1]
体外研究 (In Vitro)
PND-1186 has an IC50 of ~100 nM in breast carcinoma cells as determined by anti-phospho-specific immunoblotting to FAK Tyr-397[1]. In murine 4T1 breast carcinoma cells, FAK is important in promoting an invasive and metastatic cell phenotype. Increasing concentrations of PND-1186 (0.1 to 1.0 µM) added to 4T1 cells inhibits FAK Tyr-397 phosphorylation (pY397) and results in elevated levels of total FAK protein within 1 h[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
4T1 breast carcinoma cells
Concentration:
0.1, 0.2, 0.4, 0.6 and 1.0 µM
Incubation Time:
1 hour
Result:
Inhibited FAK Tyr-397 phosphorylation (pY397) and resulted in elevated levels of total FAK protein.
体内研究 (In Vivo)
PND-1186 (30 mg/kg or 100 mg/kg; subcutaneously; injected subcutaneously in the neck region) inhibits 4T1 subcutaneous tumor growth by induction of apoptosis[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
BALB/c mice[1]
Dosage:
30 mg/kg or 100 mg/kg
Administration:
Injected (100 µL) subcutaneously in the neck region; every 12 h (twice-daily, b.i.d.) for 5 days.
Result:
100 mg/kg treatment significantly reduced final 4T1 tumor weight 2-fold whereas 30 mg/kg treatment slightly reduced final tumor weight but was not significantly different compared to control.
Clinical Trial
分子量
501.50
Formula
C25H26F3N5O3
CAS 号
1061353-68-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Tanjoni I, et al. PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments. Cancer Biol Ther. 2010 May 15;9(10):764-77.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
相关属性
溶解性
Off-white/white solid or viscous liquid depends on molecule weight;Soluble in regular aqeous solution as well as most organic solvents;
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
相关属性
溶解性
Off-white/white solid or viscous liquid depends on molecule weight;Soluble in regular aqeous solution as well as most organic solvents;
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
相关属性
溶解性
Off-white/white solid or viscous liquid depends on molecule weight;Soluble in regular aqeous solution as well as most organic solvents;
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
相关属性
溶解性
Off-white/white solid or viscous liquid depends on molecule weight;Soluble in regular aqeous solution as well as most organic solvents;
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
相关属性
溶解性
Orange/yellowsolid or viscous liquid depends on molecule weight;Soluble in regular aqeous solution as well as most organic solvents;
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
相关属性
溶解性
Orange/yellowsolid or viscous liquid depends on molecule weight;Soluble in regular aqeous solution as well as most organic solvents;
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Physical Properties:
Off-white/white solid or viscous liquid depends on molecule weight;
Soluble in regular aqeous solution as well as most organic solvents;
Storage Conditions:
Store at -20 0C, dessiccated Protect from light. Avoid frequent thaw and freeze.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Physical Properties:
Off-white/white solid or viscous liquid depends on molecule weight;
Soluble in regular aqeous solution as well as most organic solvents;
Storage Conditions:
Store at -20 0C, dessiccated Protect from light. Avoid frequent thaw and freeze.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Physical Properties:
Off-white/white solid or viscous liquid depends on molecule weight;
Soluble in regular aqeous solution as well as most organic solvents;
Storage Conditions:
Store at -20 0C, dessiccated Protect from light. Avoid frequent thaw and freeze.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Physical Properties:
Off-white/white solid or viscous liquid depends on molecule weight;
Soluble in regular aqeous solution as well as most organic solvents;
Storage Conditions:
Store at -20 0C, dessiccated Protect from light. Avoid frequent thaw and freeze.
PF-562271 (VS-6062) is shown to be a 30- to 120-nM inhibitor of CDK2/E, CDK5/p35, CDK1/B, and CDK3/E in recombinant enzyme assays, in cell-based assays evaluating the role of CDKs, a 48-hour exposure of 3.3 μM PF-562271 is required to alter cell cycle progression. PF-562271 is potent in an inducible cell-based assay measuring phospho-FAK with a IC50 of 5 nM[1]. PF-562271, a selective inhibitor of both FAK and proline-rich tyrosine kinase 2 (PYK2), a FAK-related family member, on cell growth and colony formation in Ewing sarcoma cell lines. Seven cell lines are treated for 5 days with PF-562271 across a range of concentrations using 2-fold serial dilutions. Treatment with PF-562271 impaires cell viability in all cell lines, with an average IC50 of 2.4 μM after 3 days of treatment. TC32 and A673 are the 2 most sensitive cell lines, with IC50 concentrations of 2.1 and 1.7 μM, respectively[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
PF-562271 inhibits FAK phosphorylation in vivo in a dose-dependent fashion (calculated EC50 of 93 ng/mL, total) after p.o. administration to tumor-bearing mice[1]. Rats that receive PF-562271 demonstrate a decrease in tumor growth after 2 weeks of treatment with signs of bone healing as evidenced by the deposition of new bone (cortical and cancellous) at sites previously damaged by the tumor[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
507.49
Formula
C21H20F3N7O3S
CAS 号
717907-75-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Roberts WG, et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res, 2008, 68(6), 1935-1944.
[2]. Crompton BD, et al. High-throughput tyrosine kinase activity profiling identifies FAK as a candidate therapeutic target in Ewing sarcoma. Cancer Res. 2013 May 1;73(9):2873-83.
[3]. Bagi CM, et al. Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases. Cancer. 2008 May 15;112(10):2313-21.
Cell Assay [2]
Ewing sarcoma cells are plated in 10-cm dishes, allowed to adhere for 24 hours, and then treated with PF-562271, PD0325901, or BMS-354825. ATP content is measured as a surrogate for cell number using the CellTiter-Glo Luminescent Cell Viability Assay. Luminescence readings are obtained using the FLUOstar Omega microplate reader. For experiments with small-molecule treatment, 1.25×103 Ewing sarcoma cells are seeded in each well and treated with a range of concentrations. IC50 values are calculated from ATP measurements obtained after 3 days of treatment using log-transformed, normalized data in GraphPad Prism 5.0. Cell lines are also treated with compound in 6-cm dishes, trypsinized, and counted by light microscopy using trypan blue exclusion. For experiments using shRNA-transduced cells, 1.25×103 cells are seeded per well into 384-well plates on day 3 posttransduction. ATP content is measured on days 3, 6, and 8 posttransduction[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1][3]
Mice[1] Athymic female mice (CD-1 Nu/Nu, ~20 grams) are used for all in vivo studies. Exponentially growing cells are trypsinized and resuspended in sterile PBS and inoculated s.c. (1×106 cells per mouse in 200 μL) into the right flank of mice. Animals bearing tumors of 150 mm3 in size are divided into groups receiving either vehicle (5% Gelucire) or PF-562,271 (diluted in vehicle), and dosed by p.o. gavage. Animal body weight and tumor measurements are obtained every 2 d. Tumor volume (mm3) is measured with Vernier calipers and calculated using the formula: length (mm)×width (mm)×width (mm)×0.5. Percent growth inhibition. For all tumor growth inhibition experiments, 8 to 10 mice per dose group are used. A Student’s t test is used to determine the P value. Rats[3] Nude (Crl:NIH-rnu) female rats are used. PF-562271 is formulated for oral dosing using 0.5% methyl-cellulose. On the first day of dosing, rats receive a single dose of PF-562271 (10 mg/kg) by oral gavage. Based on the exposure levels at 1 hour after dosing, the dose is reduced to 5 mg/kg. From the second day onward, rats are dosed daily with 5 mg/kg by oral gavage for 28 days. Dosing is initiated 2 weeks after tumor inoculation and only after the presence of tumors is confirmed by radiography. The presence of the tested compound in serum is confirmed during the course of the study.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Roberts WG, et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res, 2008, 68(6), 1935-1944.
[2]. Crompton BD, et al. High-throughput tyrosine kinase activity profiling identifies FAK as a candidate therapeutic target in Ewing sarcoma. Cancer Res. 2013 May 1;73(9):2873-83.
[3]. Bagi CM, et al. Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases. Cancer. 2008 May 15;112(10):2313-21.
Vinylsulfone (VS) functionalized polyethylene glycol (VS PEG) is a thiol (-SH) group reactive PEG derivative that can be used to modify biomolecules or other materials via their available thiol groups. VS group react with free thiol groups easily in aqueous buffer between pH 6.5~8.5 at room temperature.
Physical Properties:
Off-white/white solid or viscous liquid depends on molecule weight;
Soluble in regular aqeous solution as well as most organic solvents;
Storage Conditions:
Store at -20 0C, dessiccated Protect from light. Avoid frequent thaw and freeze.
