SNS-314 is a potent and selective aurora kinase inhibitor with IC50s of 9, 31, and 6 nM for aurora A, B and C, respectively[1].
IC50 & Target[1]
Aurora A
9 nM (IC50)
Aurora B
31 nM (IC50)
Aurora C
6 nM (IC50)
体外研究 (In Vitro)
SNS-314 blocks proliferation in a broad panel of tumor cell lines (HCT116, A2780, PC-3, HeLa, MDA-MB-231, H-1299, and HT29) with IC50 values ranging from 1.8 nM in A2780 ovarian cancer cells to 24 nM in HT29 colon cancer cells[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
In the HCT116 human colon cancer xenograft model, administration of 50 and 100 mg/kg SNS-314 leads to dose-dependent inhibition of histone H3 phosphorylation for at least 10 h. SNS-314 shows significant tumor growth inhibition in a dose dependent manner under a variety of dosing schedules including weekly, bi-weekly, and 5 days on/9 days off[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
430.93
Formula
C18H15ClN6OS2
CAS 号
1057249-41-8
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]. Oslob JD, et al. Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4.
[2]. Arbitrario JP, et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
SNS-314 is a potent and selective aurora kinase inhibitor with IC50s of 9, 31, and 6 nM for aurora A, B and C, respectively[1].
IC50 & Target[1]
Aurora A
9 nM (IC50)
Aurora B
31 nM (IC50)
Aurora C
6 nM (IC50)
体外研究 (In Vitro)
SNS-314 blocks proliferation in a broad panel of tumor cell lines (HCT116, A2780, PC-3, HeLa, MDA-MB-231, H-1299, and HT29) with IC50 values ranging from 1.8 nM in A2780 ovarian cancer cells to 24 nM in HT29 colon cancer cells[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)
In the HCT116 human colon cancer xenograft model, administration of 50 and 100 mg/kg SNS-314 leads to dose-dependent inhibition of histone H3 phosphorylation for at least 10 h. SNS-314 shows significant tumor growth inhibition in a dose dependent manner under a variety of dosing schedules including weekly, bi-weekly, and 5 days on/9 days off[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.
分子量
430.93
Formula
C18H15ClN6OS2
CAS 号
1057249-41-8
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]. Oslob JD, et al. Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4.
[2]. Arbitrario JP, et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
SNS-314 is a potent and selective aurora kinase inhibitor with IC50s of 9, 31, and 6 nM for aurora A, B and C, respectively[1].
IC50 & Target[1]
Aurora A
9 nM (IC50)
Aurora B
31 nM (IC50)
Aurora C
6 nM (IC50)
体外研究 (In Vitro)
SNS-314 blocks proliferation in a broad panel of tumor cell lines (HCT116, A2780, PC-3, HeLa, MDA-MB-231, H-1299, and HT29) with IC50 values ranging from 1.8 nM in A2780 ovarian cancer cells to 24 nM in HT29 colon cancer cells[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
In the HCT116 human colon cancer xenograft model, administration of 50 and 100 mg/kg SNS-314 leads to dose-dependent inhibition of histone H3 phosphorylation for at least 10 h. SNS-314 shows significant tumor growth inhibition in a dose dependent manner under a variety of dosing schedules including weekly, bi-weekly, and 5 days on/9 days off[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
430.93
Formula
C18H15ClN6OS2
CAS 号
1057249-41-8
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]. Oslob JD, et al. Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4.
[2]. Arbitrario JP, et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
Voreloxin (SNS-595; Vosaroxin; AG 7352) 是一种新创的拓扑异构酶 II (topoisomerase II) 抑制剂，能够诱导 DNA 双链断裂，阻滞 G2 期，最终细胞凋亡。
Voreloxin Chemical Structure
CAS No. : 175414-77-4
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
Voreloxin 的其他形式现货产品:
Voreloxin Hydrochloride
生物活性
Voreloxin (SNS-595; Vosaroxin; AG 7352) is a first-in-class topoisomerase II inhibitor that intercalates DNA and induces site-selective DNA DSB, G2 arrest, and apoptosis.
IC50 & Target
Topoisomerase II
体外研究 (In Vitro)
Voreloxin is a first-in-class topoisomerase II poison and inhibitor that intercalates DNA and induces site-selective DNA DSB, G2 arrest, and apoptosis. Voreloxin (0.1-20 µM) inhibits topoisomerase II activity and induces site-selective DNA DSB in CCRF-CEM cells. Voreloxin (0.11, 0.33, 1, 3 µM) induces G2 arrest partially through topoisomerase II in A549 lung cancer cell line. Voreloxin cytotoxic activity requires DNA intercalation. However, Voreloxin (1-9 µM) does not generate significant levels of ROS[1]. Voreloxin has potent cytotoxic activity in AML cell lines MV4-11 and HL-60, with IC50s of 95 ± 8 nM and 884 ± 114 nM, respectively. Voreloxin in combination with cytarabine shows additive or synergistic activity in acute leukemia cell lines[2]. Voreloxin is active on the primary acute myeloid leukemia (AML) with a mean LD50 of 2.3 μM. The LD50 for voreloxin in myeloid cell lines NB4 and HL-60 is 0.59 μM ± 0.25 μM. Voreloxin causes accumulation of cells in the S and G2 phases of the cell cycle and acts on topoisomerase II[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Voreloxin (20 mg/kg, i.v.) alone results in 80% reduction in bone marrow cellularity of CD-1 mice by administration one dose every 4 days repeated twice (q4d ×2). voreloxin at 10 mg/kg in combination with cytarabine causes ablation of the marrow, dilation of sinusoids, and infiltration of adipocytes in mice. Voreloxin (20 mg/kg, i.v.) combined with cytarabine causes a reversible decrease in myeloid and lymphoid cells in bone marrow and peripheral blood CD-1 mice. voreloxin (10 mg/kg, q4d ×2) and cytarabine in combination causes reversible neutropenia with a more modest impact on platelets CD-1 mice[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
401.44
Formula
C18H19N5O4S
CAS 号
175414-77-4
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]. Hotinski AK, et al. Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and refractory acute myeloid leukaemia. Expert Opin Pharmacother. 2015 Jun;16(9):1395-402.
[2]. Scatena CD, et al. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemother Pharmacol. 2010 Oct;66(5):881-8.
[3]. Walsby EJ, et al. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine. Haematologica. 2011 Mar;96(3):393-9.
Cell Assay [3]
In vitro toxicity assays are performed on primary AML mononuclear cells over a 48 h period using a MTS cell proliferation assay. Lethal doses (LD50) are calculated. Cells are treated with voreloxin (31.25 nM to 4 μM) and Ara-C (62.5 nM to 8 μM) by serial dilution and incubated for 48 h in a final volume of 90 μL. Following the incubation, 20 μL of MTS reagent are added and the reaction is incubated for a further 4 h. The absorbance of the reaction after this time is read by spectrophotometry at 490 nm and the percentage of viable cells calculated relative to untreated control cells in the same assay. IC50 values are calculated using Calcusyn software[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [2]
Animals are weighed, randomized by body weight, and assigned to the study groups before initiation of treatment. Voreloxin is administered intravenously (IV) at 10 or 20 mg/kg once on day zero and once on day four (q4d ×2). Cytarabine is administered subcutaneously (SC) at 20 or 60 mg/kg every 8 h on day zero and day four (tid q4d ×2). Tissues and blood are sampled on days 6, 8, and 12 from at least three and not greater than ten animals per treatment group. Femurs are placed in Streck Tissue Fixative solution, or in 10% formalin solution for 24-48 h followed by a 70% dehydrant (ethanol, isopropanol, methanol). Femurs are decalcified, paraffin embedded, and sectioned at Biopathology Labs. The four micron sections are stained with hematoxylin-eosin (H&E). H&E stained femurs are examined and percent cellularity of the bone marrow is determined. Digital photographs of representative femur sections are taken on a Leica DM2000 microscope using Image-Pro Plus v6.1 software[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Hotinski AK, et al. Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and refractory acute myeloid leukaemia. Expert Opin Pharmacother. 2015 Jun;16(9):1395-402.
[2]. Scatena CD, et al. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemother Pharmacol. 2010 Oct;66(5):881-8.
[3]. Walsby EJ, et al. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine. Haematologica. 2011 Mar;96(3):393-9.
Voreloxin (SNS-595; Vosaroxin; AG 7352) 是一种新创的拓扑异构酶 II (topoisomerase II) 抑制剂，能够诱导 DNA 双链断裂，阻滞 G2 期，最终细胞凋亡。
Voreloxin Chemical Structure
CAS No. : 175414-77-4
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
Voreloxin 的其他形式现货产品:
Voreloxin Hydrochloride
生物活性
Voreloxin (SNS-595; Vosaroxin; AG 7352) is a first-in-class topoisomerase II inhibitor that intercalates DNA and induces site-selective DNA DSB, G2 arrest, and apoptosis.
IC50 & Target
Topoisomerase II
体外研究 (In Vitro)
Voreloxin is a first-in-class topoisomerase II poison and inhibitor that intercalates DNA and induces site-selective DNA DSB, G2 arrest, and apoptosis. Voreloxin (0.1-20 µM) inhibits topoisomerase II activity and induces site-selective DNA DSB in CCRF-CEM cells. Voreloxin (0.11, 0.33, 1, 3 µM) induces G2 arrest partially through topoisomerase II in A549 lung cancer cell line. Voreloxin cytotoxic activity requires DNA intercalation. However, Voreloxin (1-9 µM) does not generate significant levels of ROS[1]. Voreloxin has potent cytotoxic activity in AML cell lines MV4-11 and HL-60, with IC50s of 95 ± 8 nM and 884 ± 114 nM, respectively. Voreloxin in combination with cytarabine shows additive or synergistic activity in acute leukemia cell lines[2]. Voreloxin is active on the primary acute myeloid leukemia (AML) with a mean LD50 of 2.3 μM. The LD50 for voreloxin in myeloid cell lines NB4 and HL-60 is 0.59 μM ± 0.25 μM. Voreloxin causes accumulation of cells in the S and G2 phases of the cell cycle and acts on topoisomerase II[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.
体内研究 (In Vivo)
Voreloxin (20 mg/kg, i.v.) alone results in 80% reduction in bone marrow cellularity of CD-1 mice by administration one dose every 4 days repeated twice (q4d ×2). voreloxin at 10 mg/kg in combination with cytarabine causes ablation of the marrow, dilation of sinusoids, and infiltration of adipocytes in mice. Voreloxin (20 mg/kg, i.v.) combined with cytarabine causes a reversible decrease in myeloid and lymphoid cells in bone marrow and peripheral blood CD-1 mice. voreloxin (10 mg/kg, q4d ×2) and cytarabine in combination causes reversible neutropenia with a more modest impact on platelets CD-1 mice[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.
Clinical Trial
分子量
401.44
Formula
C18H19N5O4S
CAS 号
175414-77-4
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]. Hotinski AK, et al. Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and refractory acute myeloid leukaemia. Expert Opin Pharmacother. 2015 Jun;16(9):1395-402.
[2]. Scatena CD, et al. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemother Pharmacol. 2010 Oct;66(5):881-8.
[3]. Walsby EJ, et al. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine. Haematologica. 2011 Mar;96(3):393-9.
Cell Assay [3]
In vitro toxicity assays are performed on primary AML mononuclear cells over a 48 h period using a MTS cell proliferation assay. Lethal doses (LD50) are calculated. Cells are treated with voreloxin (31.25 nM to 4 μM) and Ara-C (62.5 nM to 8 μM) by serial dilution and incubated for 48 h in a final volume of 90 μL. Following the incubation, 20 μL of MTS reagent are added and the reaction is incubated for a further 4 h. The absorbance of the reaction after this time is read by spectrophotometry at 490 nm and the percentage of viable cells calculated relative to untreated control cells in the same assay. IC50 values are calculated using Calcusyn software[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.
Animal Administration [2]
Animals are weighed, randomized by body weight, and assigned to the study groups before initiation of treatment. Voreloxin is administered intravenously (IV) at 10 or 20 mg/kg once on day zero and once on day four (q4d ×2). Cytarabine is administered subcutaneously (SC) at 20 or 60 mg/kg every 8 h on day zero and day four (tid q4d ×2). Tissues and blood are sampled on days 6, 8, and 12 from at least three and not greater than ten animals per treatment group. Femurs are placed in Streck Tissue Fixative solution, or in 10% formalin solution for 24-48 h followed by a 70% dehydrant (ethanol, isopropanol, methanol). Femurs are decalcified, paraffin embedded, and sectioned at Biopathology Labs. The four micron sections are stained with hematoxylin-eosin (H&E). H&E stained femurs are examined and percent cellularity of the bone marrow is determined. Digital photographs of representative femur sections are taken on a Leica DM2000 microscope using Image-Pro Plus v6.1 software[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.
参考文献
[1]. Hotinski AK, et al. Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and refractory acute myeloid leukaemia. Expert Opin Pharmacother. 2015 Jun;16(9):1395-402.
[2]. Scatena CD, et al. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemother Pharmacol. 2010 Oct;66(5):881-8.
[3]. Walsby EJ, et al. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine. Haematologica. 2011 Mar;96(3):393-9.
Voreloxin (SNS-595; Vosaroxin; AG 7352) 是一种新创的拓扑异构酶 II (topoisomerase II) 抑制剂，能够诱导 DNA 双链断裂，阻滞 G2 期，最终细胞凋亡。
Voreloxin Chemical Structure
CAS No. : 175414-77-4
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
Voreloxin 的其他形式现货产品:
Voreloxin Hydrochloride
生物活性
Voreloxin (SNS-595; Vosaroxin; AG 7352) is a first-in-class topoisomerase II inhibitor that intercalates DNA and induces site-selective DNA DSB, G2 arrest, and apoptosis.
IC50 & Target
Topoisomerase II
体外研究 (In Vitro)
Voreloxin is a first-in-class topoisomerase II poison and inhibitor that intercalates DNA and induces site-selective DNA DSB, G2 arrest, and apoptosis. Voreloxin (0.1-20 µM) inhibits topoisomerase II activity and induces site-selective DNA DSB in CCRF-CEM cells. Voreloxin (0.11, 0.33, 1, 3 µM) induces G2 arrest partially through topoisomerase II in A549 lung cancer cell line. Voreloxin cytotoxic activity requires DNA intercalation. However, Voreloxin (1-9 µM) does not generate significant levels of ROS[1]. Voreloxin has potent cytotoxic activity in AML cell lines MV4-11 and HL-60, with IC50s of 95 ± 8 nM and 884 ± 114 nM, respectively. Voreloxin in combination with cytarabine shows additive or synergistic activity in acute leukemia cell lines[2]. Voreloxin is active on the primary acute myeloid leukemia (AML) with a mean LD50 of 2.3 μM. The LD50 for voreloxin in myeloid cell lines NB4 and HL-60 is 0.59 μM ± 0.25 μM. Voreloxin causes accumulation of cells in the S and G2 phases of the cell cycle and acts on topoisomerase II[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Voreloxin (20 mg/kg, i.v.) alone results in 80% reduction in bone marrow cellularity of CD-1 mice by administration one dose every 4 days repeated twice (q4d ×2). voreloxin at 10 mg/kg in combination with cytarabine causes ablation of the marrow, dilation of sinusoids, and infiltration of adipocytes in mice. Voreloxin (20 mg/kg, i.v.) combined with cytarabine causes a reversible decrease in myeloid and lymphoid cells in bone marrow and peripheral blood CD-1 mice. voreloxin (10 mg/kg, q4d ×2) and cytarabine in combination causes reversible neutropenia with a more modest impact on platelets CD-1 mice[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
401.44
Formula
C18H19N5O4S
CAS 号
175414-77-4
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]. Hotinski AK, et al. Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and refractory acute myeloid leukaemia. Expert Opin Pharmacother. 2015 Jun;16(9):1395-402.
[2]. Scatena CD, et al. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemother Pharmacol. 2010 Oct;66(5):881-8.
[3]. Walsby EJ, et al. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine. Haematologica. 2011 Mar;96(3):393-9.
Cell Assay [3]
In vitro toxicity assays are performed on primary AML mononuclear cells over a 48 h period using a MTS cell proliferation assay. Lethal doses (LD50) are calculated. Cells are treated with voreloxin (31.25 nM to 4 μM) and Ara-C (62.5 nM to 8 μM) by serial dilution and incubated for 48 h in a final volume of 90 μL. Following the incubation, 20 μL of MTS reagent are added and the reaction is incubated for a further 4 h. The absorbance of the reaction after this time is read by spectrophotometry at 490 nm and the percentage of viable cells calculated relative to untreated control cells in the same assay. IC50 values are calculated using Calcusyn software[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [2]
Animals are weighed, randomized by body weight, and assigned to the study groups before initiation of treatment. Voreloxin is administered intravenously (IV) at 10 or 20 mg/kg once on day zero and once on day four (q4d ×2). Cytarabine is administered subcutaneously (SC) at 20 or 60 mg/kg every 8 h on day zero and day four (tid q4d ×2). Tissues and blood are sampled on days 6, 8, and 12 from at least three and not greater than ten animals per treatment group. Femurs are placed in Streck Tissue Fixative solution, or in 10% formalin solution for 24-48 h followed by a 70% dehydrant (ethanol, isopropanol, methanol). Femurs are decalcified, paraffin embedded, and sectioned at Biopathology Labs. The four micron sections are stained with hematoxylin-eosin (H&E). H&E stained femurs are examined and percent cellularity of the bone marrow is determined. Digital photographs of representative femur sections are taken on a Leica DM2000 microscope using Image-Pro Plus v6.1 software[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Hotinski AK, et al. Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and refractory acute myeloid leukaemia. Expert Opin Pharmacother. 2015 Jun;16(9):1395-402.
[2]. Scatena CD, et al. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemother Pharmacol. 2010 Oct;66(5):881-8.
[3]. Walsby EJ, et al. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine. Haematologica. 2011 Mar;96(3):393-9.
Vecabrutinib (SNS-062) is a potent, noncovalent BTK and ITK inhibitor, with Kd values of 0.3 nM and 2.2 nM, respectively. Vecabrutinib shows an IC50 of 24 nM for ITK[1][2].
Vecabrutinib inhibits pBTK in human whole blood with an average IC50 of 50 nM. Vecabrutinib inhibits WT and C481S BTK with similar IC50s (pBTK IC50s: WT BTK 2.9 nM, C481S BTK 4.4 nM)[1]. In a recombinant kinase assay, IC50s of Vecabrutinib against WT BTK and C481S BTK are 4.6 nM and 1.1 nM. Vecabrutinib retains activity against the mutated BTK variant. Vecabrutinib is six times more potent than PCI-32765 and greater than 640 times more potent than acalabrutinib against C481S BTK. Vecabrutinib demonstrates dose-dependent inhibition of BTK in primary patient CLL cells comparable to PCI-32765 via immunoblot for BTK phosphorylation. Vecabrutinib decreases viability of primary CLL cells in the presence of HS5 stromal protection by 5.5%[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)
Vecabrutinib has good oral bioavailability in rat and dog (%F ≥ 40%) and a terminal half-life of 5 to 6 hours. Vecabrutinib is well tolerated with continuous drug levels and at exposures much greater than those achieved for PCI-32765[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
529.92
Formula
C22H24ClF4N7O2
CAS 号
1510829-06-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Minke E. Binnerts, et al. Abstract C186: SNS-062 is a potent noncovalent BTK inhibitor with comparable activity against wild type BTK and BTK with an acquired resistance mutation. Molecular Cancer Therapeutics. December 2015 Volume 14, Issue 12 Supplement 2
[2]. Catherine A. Fabian, et al. Abstract 1207: SNS-062 demonstrates efficacy in chronic lymphocytic leukemia in vitro and inhibits C481S mutated Bruton tyrosine kinase. Cancer Research July 2017 Volume 77, Issue 13 Supplement
SNS-314 mesylate is a potent and selective aurora kinase inhibitor with IC50s of 9, 31, and 6 nM for aurora A, B and C, respectively[1].
IC50 & Target[1]
Aurora A
9 nM (IC50)
Aurora B
31 nM (IC50)
Aurora C
6 nM (IC50)
体外研究 (In Vitro)
SNS-314 blocks proliferation in a broad panel of tumor cell lines (HCT116, A2780, PC-3, HeLa, MDA-MB-231, H-1299, and HT29) with IC50 values ranging from 1.8 nM in A2780 ovarian cancer cells to 24 nM in HT29 colon cancer cells[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)
In the HCT116 human colon cancer xenograft model, administration of 50 and 100 mg/kg SNS-314 leads to dose-dependent inhibition of histone H3 phosphorylation for at least 10 h. SNS-314 shows significant tumor growth inhibition in a dose dependent manner under a variety of dosing schedules including weekly, bi-weekly, and 5 days on/9 days off[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.
Clinical Trial
分子量
527.04
Formula
C19H19ClN6O4S3
CAS 号
1146618-41-8
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. Oslob JD, et al. Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4.
[2]. Arbitrario JP, et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
Kinase Assay [2]
A homogeneous time-resolved fluorescence (HTRF)-based biochemical IC50 assay is used to test for the kinase activity of the three isoforms of Aurora (A, B, and C) in the presence of SNS-314. A biotin-conjugated histone H3 peptide is used as substrate. Aurora-A kinase (7.5 nM) is assayed in 10 mM Tris–HCl pH 7.2, 10 mM MgCl2, 0.1% BSA, 0.05% Tween 20, 1 mM DTT, 120 nM biotinylated peptide ARTKQTARKSTGGKAPRKQLA-GGK-biotin, 6 μM ATP (2×the Km for the enzyme) for 1 h at 25°C. The reaction is stopped with 200 mM EDTA. Aurora-B and Aurora-C are assayed at 5 nM enzyme concentration, 120 nM biotinylated peptide, and 300 lM ATP (29 the Km for the enzymes) for 1 h at 25°C[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.
Cell Assay [2]
HCT116 cells are treated with various concentrations of SNS-314 for 96 hours. cells are incubated with BrdU for 2 h at 37°C. Cell proliferation activity is evaluated by chemiluminescence detection of BrdU incorporated in DNA[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 [2]
Mice: Tumor mice are treated with vehicle or SNS-314. Animals are weighed, monitored for signs or symptoms of toxic effects, and measured for tumor volumes twice weekly until an end point is met[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.
参考文献
[1]. Oslob JD, et al. Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4.
[2]. Arbitrario JP, et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
SNS-032 (BMS-387032) is a potent and selective inhibitor of CDK2, CDK7, and CDK9 with IC50s of 38 nM, 62 nM and 4 nM, respectively. SNS-032 has antitumor effect[1].
IC50 & Target
CDK9
4 nM (IC50)
CDK2
38 nM (IC50)
CDK7
62 nM (IC50)
CDK1
480 nM (IC50)
CDK4
925 nM (IC50)
体外研究 (In Vitro)
SNS-032 has low sensitivity to CDK1 and CDK4 with IC50 of 480 nM and 925 nM, respectively. SNS-032 effectively kills chronic lymphocytic leukemia cells in vitro regardless of prognostic indicators and treatment history. Compared with flavopiridol and roscovitine, SNS-032 is more potent, both in inhibition of RNA synthesis and at induction of apoptosis. SNS-032 activity is readily reversible; removal of SNS-032 reactivates RNA polymerase II, which led to resynthesis of Mcl-1 and cell survival[1]. SNS-032 inhibits three dimensional capillary network formations of endothelial cells. SNS-032 completely prevents U87MG cell–mediated capillary formation of HUVECs. In addition, SNS-032 significantly prevents the production of VEGF in both cell lines, SNS-032 prevents in vitro angiogenesis, and this action is attributable to blocking of VEGF. Preclinical studies have shown that SNS-032 induces cell cycle arrest and apoptosis across multiple cell lines[2]. SNS-032 blocks the cell cycle via inhibition of CDKs 2 and 7, and transcription via inhibition of CDKs 7 and 9. SNS-032 activity is unaffected by human serum[3]. SNS-032 induces a dose-dependent increase in annexin V staining and caspase-3 activation. At the molecular level, SNS-032 induces a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and inhibits the expression of CDK2 and CDK9 and dephosphorylated CDK7[5].
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)
SNS-032 (15 mg/kg, i.p.) inhibits both xenografted BaF3-T674I cells and KBM5-T315I cells in vivo. SNS-032 abrogates the growth of tumors transplanted in nude mice with downregulation of T674I PDGFRα and T315I-Bcr-Abl[4].
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
380.53
Formula
C17H24N4O2S2
CAS 号
345627-80-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Chen R, et al. Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
[2]. Ali MA, et al. SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor. Neoplasia. 2007 May;9(5):370-81.
[3]. Conroy A, et al. SNS-032 is a potent and selective CDK 2, 7 and 9 inhibitor that drives target modulation in patient samples. Cancer Chemother Pharmacol. 2009 Sep;64(4):723-32.
[4]. Wu Y, et al. Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor α and bcr-abl oncogene addiction in malignant hematologic cells.Clin Cancer Res. 2012 Apr 1;18(7):1966-78. Epub 2012 Mar 23.
[5]. Walsby E, et al. The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells. Leukemia. 2011 Mar;25(3):411-9. Epub 2011 Jan 7.
Cell Assay [2]
Cell Titer-Glo (CTG) luminescent assay is performed to measure the growth curves of both HUVECs and U87MG cells. U87MG cells and HUVECs (2×103 cells/well) are seeded in a 96-well microplate in a final volume of 100 mL. After 24 hours, cells are treated with various doses of SNS-032 (0-0.5 mM) for 24, 48, or 72 hours. After completion of the treatment, 100 mL of CTG solution is added to each well and incubated for 20 minutes at room temperature in the dark. Lysate (50 mL) is transferred to a 96-well white plate, and luminescence is measured by POLARstar OPTIMA. Percent cell growth is calculated by considering 100% growth at the time of SNS-032 addition.
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 [4]
Nude nu/nu BALB/c mice are housed in barrier facilities with a 12-hour light-dark cycle, with food and water available ad libitum. A mixture of 1×107 of BaF3-T674I cells with Matrigel or KBM5-T315I cells (3×107) are inoculated subcutaneously on the flanks of 4- to 6-week-old male nude mice. Tumors are measured every other day with use of calipers. Tumor volumes are calculated by the following formula: a2×b×0.4, where a is the smallest diameter and b is the diameter perpendicular to a. Four days after subcutaneous inoculation, when tumors are palpable (appr 100 mm3), mice are randomized to receive treatment with vehicle (tissue culture medium containing DMSO 0.1% v/v) or SNS-032 (15 mg/kg injected intraperitoneally every 2 days) for about 2 weeks. SNS-032 is dissolved in tissue culture grade DMSO before dilution. The body weight, feeding behavior, and motor activity of each animal are monitored as indicators of general health. The animals are then euthanized, and tumor xenografts are immediately removed, weighed, stored, and fixed.
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]. Chen R, et al. Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
[2]. Ali MA, et al. SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular endothelial growth factor. Neoplasia. 2007 May;9(5):370-81.
[3]. Conroy A, et al. SNS-032 is a potent and selective CDK 2, 7 and 9 inhibitor that drives target modulation in patient samples. Cancer Chemother Pharmacol. 2009 Sep;64(4):723-32.
[4]. Wu Y, et al. Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor α and bcr-abl oncogene addiction in malignant hematologic cells.Clin Cancer Res. 2012 Apr 1;18(7):1966-78. Epub 2012 Mar 23.
[5]. Walsby E, et al. The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells. Leukemia. 2011 Mar;25(3):411-9. Epub 2011 Jan 7.
THAL-SNS-032 is a selective CDK9 degrader PROTAC consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative that binds the E3 ubiquitin ligase Cereblon (CRBN)[1].
IC50 & Target
CDK9[1]
体外研究 (In Vitro)
THAL-SNS-032 selectively induces degradation of CDK9[1]. THAL-SNS-032 diminishes elongating polymerase II[1]. THAL-SNS-032 inhibits proliferation of MOLT4 cells with an IC50 of 50 nM[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.
分子量
869.02
Formula
C40H52N8O10S2
CAS 号
2139287-33-3
运输条件
Room temperature in continental US; may vary elsewhere.
