CYH33 methanesulfonate is an orally active, highly selective PI3Kα inhibitor with IC50s of 5.9 nM/598 nM/78.7 nM/225 nM against α/β/δ/γ isoform, respectively. CYH33 methanesulfonate inhibits phosphorylation of Akt, ERK and induces significant G1 phase arrest in breast cancer cells and non-small cell lung cancer (NSCLC) cells. CYH33 methanesulfonate has potent activity against solid tumors[1][2][3].
IC50 & Target[1]
PI3Kα
5.9 nM (IC50)
PI3Kβ
598 nM (IC50)
PI3Kδ
78.7 nM (IC50)
PI3Kγ
225 nM (IC50)
体外研究 (In Vitro)
CYH33 methanesulfonate inhibits cell proliferation with IC50s below 1 μM in 56% (18/32) of the breast cancer cell lines[2]. CYH33 (0.012-1 μM; for 24 hours) methanesulfonate significantly arrests T47D and MCF7 cells in G1 phase in a concentration-dependent manner[2]. CYH33 (4-1000 nM; 1 hour) methanesulfonate concurrently inhibits phosphorylation of ERK and Akt in both T47D and MCF7 cells[2]. CYH33 (0.11-1 μM; 24 hours) methanesulfonate fails to induce apoptosis in MCF7 and MDA-MB-231 cells[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cycle Analysis[2]
Cell Line:
Sensitive T47D, MCF7 and resistant MDA-MB-231 cells
Concentration:
0.012, 0.037, 0.11, 0.33, 1 μM
Incubation Time:
For 24 hours
Result:
Arrested T47D and MCF7 cells in G1 phase in a concentration-dependent manner, accompanied with concomitant reduced cell population in S phase. Had little effect on cell cycle distribution in resistant MDA-MB-231 cells.
Western Blot Analysis[2]
Cell Line:
Sensitive T47D, MCF7 and resistant MDA-MB-231 cells
Concentration:
4, 12, 37, 111, 333, 1000 nM
Incubation Time:
1 hour
Result:
Concurrently inhibited phosphorylation of ERK and Akt in both T47D and MCF7 cells, whereas it had little effect on phosphorylated ERK (pERK) in MDA-MB-231 cells up to 1 μM.
体内研究 (In Vivo)
CYH33 (2-20 mg/kg; oral; once a day for 21 days) methanesulfonate potently restrains tumor growth in mice bearing human breast cancer cell xenografts[2]. Single administration of CYH33 (20 mg/kg; oral) methanesulfonate significantly down-regulates the level of phosphorylated Akt in tumor tissues, demonstrating the suppression of PI3K signaling in nude mice[2]. CYH33 (10 mg/kg; oral; once a day for 18-d or 20-d respectively) methanesulfonate delays the restoration of blood glucose and area under the curve (AUC) of blood glucose increased upon CYH33 treatment in T47D xenografts and R26-Pik3caH1047R;MMTV-Cre mice[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
SCID mice aged 4-6 weeks bearing human breast cancer T47D xenografts[2]
Dosage:
2, 5, 10, 20 mg/kg
Administration:
Oral; once a day for 21 days
Result:
Displayed marginal inhibitory effect on the tumor growth at lower doses (2 and 5 mg/kg) and significantly attenuated tumor growth at the dose of 10 or 20 mg/kg, yielding T/C values of 58.36% and 49.42% respectively.
分子量
694.70
Formula
C25H33F3N8O8S2
CAS 号
1494684-33-1
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]. Haoyue Xiang, et al. Abstract LB-268: Discovery of clinical candidate methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate (CYH33) : A highly potent and selective PI3K alpha inhibitor for the treatment of advanced solid tumors. AACR Annual Meeting 2018; April 14-18, 2018
[2]. Xue-Ling Liu, et al. Decrease in Phosphorylated ERK Indicates the Therapeutic Efficacy of a Clinical PI3Kα-selective Inhibitor CYH33 in Breast Cancer. Cancer Lett. 2018 Oct 1;433:273-282.
[3]. Yuxiang Wang, et al. Simultaneous inhibition of PI3Kα and CDK4/6 synergistically suppresses KRAS-mutated non-small cell lung cancer. Cancer Biol Med. 2019 Feb;16(1):66-83.
CYH33 is an orally active, highly selective PI3Kα inhibitor with IC50s of 5.9 nM/598 nM/78.7 nM/225 nM against α/β/δ/γ isoform, respectively. CYH33 inhibits phosphorylation of Akt, ERK and induces significant G1 phase arrest in breast cancer cells and non-small cell lung cancer (NSCLC) cells. CYH33 has potent activity against solid tumors[1][2][3].
IC50 & Target[1]
PI3Kα
5.9 nM (IC50)
PI3Kβ
598 nM (IC50)
PI3Kδ
78.7 nM (IC50)
PI3Kγ
225 nM (IC50)
体外研究 (In Vitro)
CYH33 inhibits cell proliferation with IC50s below 1 μM in 56% (18/32) of the breast cancer cell lines[2]. CYH33 (0.012-1 μM; for 24 hours) significantly arrests T47D and MCF7 cells in G1 phase in a concentration-dependent manner[2]. CYH33 (4-1000 nM; 1 hour) concurrently inhibits phosphorylation of ERK and Akt in both T47D and MCF7 cells[2]. CYH33 (0.11-1 μM; 24 hours) fails to induce apoptosis in MCF7 and MDA-MB-231 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.
Cell Cycle Analysis[2]
Cell Line:
Sensitive T47D, MCF7 and resistant MDA-MB-231 cells
Concentration:
0.012, 0.037, 0.11, 0.33, 1 μM
Incubation Time:
For 24 hours
Result:
Arrested T47D and MCF7 cells in G1 phase in a concentration-dependent manner, accompanied with concomitant reduced cell population in S phase. Had little effect on cell cycle distribution in resistant MDA-MB-231 cells.
Western Blot Analysis[2]
Cell Line:
Sensitive T47D, MCF7 and resistant MDA-MB-231 cells
Concentration:
4, 12, 37, 111, 333, 1000 nM
Incubation Time:
1 hour
Result:
Concurrently inhibited phosphorylation of ERK and Akt in both T47D and MCF7 cells, whereas it had little effect on phosphorylated ERK (pERK) in MDA-MB-231 cells up to 1 μM.
体内研究 (In Vivo)
CYH33 (2-20 mg/kg; oral; once a day for 21 days) potently restrains tumor growth in mice bearing human breast cancer cell xenografts[2]. Single administration of CYH33 (20 mg/kg; oral) significantly down-regulates the level of phosphorylated Akt in tumor tissues, demonstrating the suppression of PI3K signaling in nude mice[2]. CYH33 (10 mg/kg; oral; once a day for 18-d or 20-d respectively) delays the restoration of blood glucose and area under the curve (AUC) of blood glucose increased upon CYH33 treatment in T47D xenografts and R26-Pik3caH1047R;MMTV-Cre 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.
Animal Model:
SCID mice aged 4-6 weeks bearing human breast cancer T47D xenografts[2]
Dosage:
2, 5, 10, 20 mg/kg
Administration:
Oral; once a day for 21 days
Result:
Displayed marginal inhibitory effect on the tumor growth at lower doses (2 and 5 mg/kg) and significantly attenuated tumor growth at the dose of 10 or 20 mg/kg, yielding T/C values of 58.36% and 49.42% respectively.
Clinical Trial
分子量
598.60
Formula
C24H29F3N8O5S
CAS 号
1494684-28-4
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]. Haoyue Xiang, et al. Abstract LB-268: Discovery of clinical candidate methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate (CYH33) : A highly potent and selective PI3K alpha inhibitor for the treatment of advanced solid tumors. AACR Annual Meeting 2018; April 14-18, 2018
[2]. Xue-Ling Liu, et al. Decrease in Phosphorylated ERK Indicates the Therapeutic Efficacy of a Clinical PI3Kα-selective Inhibitor CYH33 in Breast Cancer. Cancer Lett. 2018 Oct 1;433:273-282.
[3]. Yuxiang Wang, et al. Simultaneous inhibition of PI3Kα and CDK4/6 synergistically suppresses KRAS-mutated non-small cell lung cancer. Cancer Biol Med. 2019 Feb;16(1):66-83.
