p53-HDM2-IN-1 is a potent inhibitor of p53-HDM2 protein-protein interaction, with an IC50 of 0.103 μM. p53-HDM2-IN-1 can be used for the research of cancer[1].
分子量
786.78
Formula
C36H40F6N4O7S
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]. Tian Y, et, al. Phe19 modification of HDM2-p53 PPI inhibitors to alleviate CYP3A4 metabolism/mechanism-based inhibition liability. Bioorg Med Chem Lett. 2022 Apr 1;61:128625.
p53-HDM2-IN-1 is a potent inhibitor of p53-HDM2 protein-protein interaction, with an IC50 of 0.103 μM. p53-HDM2-IN-1 can be used for the research of cancer[1].
分子量
786.78
Formula
C36H40F6N4O7S
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]. Tian Y, et, al. Phe19 modification of HDM2-p53 PPI inhibitors to alleviate CYP3A4 metabolism/mechanism-based inhibition liability. Bioorg Med Chem Lett. 2022 Apr 1;61:128625.
p53-HDM2-IN-1 is a potent inhibitor of p53-HDM2 protein-protein interaction, with an IC50 of 0.103 μM. p53-HDM2-IN-1 can be used for the research of cancer[1].
分子量
786.78
Formula
C36H40F6N4O7S
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]. Tian Y, et, al. Phe19 modification of HDM2-p53 PPI inhibitors to alleviate CYP3A4 metabolism/mechanism-based inhibition liability. Bioorg Med Chem Lett. 2022 Apr 1;61:128625.
Siremadlin (NVP-HDM201) is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor.
体外研究 (In Vitro)
Siremadlin (NVP-HDM201) disrupts both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation[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)
Siremadlin (NVP-HDM201) is an imidazolopyrrolidinone analogue, showing a very advantageous in vivo profile. NVP-HDM201 has recently entered Phase 1 clinical trials in cancer patients[2]. Constitutive PB mutagenesis in Arf−/− mice provides a collection of spontaneous tumors with characterized insertional genetic landscapes. Tumors are allografted in large cohorts of mice to assess the pharmacologic effects of Siremadlin (NVP-HDM201). Sixteen out of 21 allograft models are sensitive to Siremadlin (NVP-HDM201) but ultimately relapse under treatment. A comparison of tumors with acquired resistance to Siremadlin (NVP-HDM201) and untreated tumors identified 87 genes that are differentially and significantly targeted by the PB transposon[1]. Siremadlin (NVP-HDM201) administered either daily at a low dose or once at a high dose revealed a differentiated engagement of the p53 molecular response. In contrast to the daily low dose treatment regimen, the single high dose Siremadlin (NVP-HDM201) regimen results in a rapid and dramatic induction of p53-dependent PUMA expression and apoptosis. This is consistent with the finding that a single high dose Siremadlin (NVP-HDM201) treatment, administered orally or intravenously, results in a robust and sustained tumor regression. Overall, both daily and once every 3 weeks dosing regimen shows comparable long term efficacy in preclinical studies. The ongoing clinical trial is currently designed to compare both dosing regimens with regard to efficacy and tolerability[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.
Clinical Trial
分子量
555.41
Formula
C26H24Cl2N6O4
CAS 号
1448867-41-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Chapeau EA, et al. Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an Arf-/- mouse model. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3151-3156.
[2]. Furet P, et al. Discovery of a novel class of highly potent inhibitors of the p53-MDM2 interaction by structure-based design starting from a conformational argument. Bioorg Med Chem Lett. 2016 Oct 1;26(19):4837-41.
[3]. Stéphane F, et al. Abstract 1224: Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials. Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1224.
HLI373 is an efficacious Hdm2 inhibitor. HLI373 inhibits the ubiquitin ligase activity of Hdm2. HLI373 is effective in inducing apoptosis of several tumor cells that are sensitive to DNA-damaging agents[1]. Antimalarial activity[2].
IC50 & Target
Hdm2[1]; Apoptosis[1]; Antimalarial[2]
体外研究 (In Vitro)
HLI373 (3-15 μM; 15 hours) selectively kills tumor cells harboring wild type p53[1]. HLI373 (10-50 μM) stabilizes cellular Hdm2 in a dose-dependent manner. HLI373 (3 μM) activates p53 transcription[1]. HLI373 selectively inhibits auto-ubiquitylation of Hdm2[1]. Co-transfection with plasmids encoding p53 and Hdm2 results in degradation of p53. Incubation with HLI373 (5-10 μM; 8 hours) blocks p53 degradation. HLI373 increases p53 and Hdm2 protein levels in cells[1]. HLI 373 also shows lower IC50 values (below 6 μM) against both chloroquine-sensitive P. falciparum D6 strain (PfD6) and chloroquine-resistant P. falciparum W2 strain (PfW2) and exhibits early growth inhibition[2]. HLI-373 is a MDM2 inhibitor interrupting its ubiquitin E3 ligase activity, could abolish the ubiquitylation of its substrate protein p53. HLI-373 targets the C-terminus functioning as an E3 ubiquitin ligase[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
Wild type p53 mouse embryo fibroblasts (MEFs), and p53-deficient MEFs
Concentration:
3, 10, 15 μM
Incubation Time:
15 hours
Result:
Increased cell death in wild type p53 MEFs in a dose-dependent manner, p53-deficient MEFs were relatively resistant.
Western Blot Analysis[1]
Cell Line:
U2OS cells
Concentration:
5, 10 μM
Incubation Time:
8 hours
Result:
Blocked p53 degradation caused by co-transfection with plasmids encoding p53 and Hdm2.
分子量
341.41
Formula
C18H23N5O2
CAS 号
502137-98-6
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]. Jirouta Kitagaki, et al. Targeting Tumor Cells Expressing p53 With a Water-Soluble Inhibitor of Hdm2. Mol Cancer Ther. 2008 Aug;7(8):2445-54.
[2]. Jagrati Jain, et al. Inhibitors of Ubiquitin E3 Ligase as Potential New Antimalarial Drug Leads. BMC Pharmacol Toxicol. 2017 Jun 2;18(1):40.
[3]. Ying Chen, et al. MDM2 Promotes Epithelial-Mesenchymal Transition and Metastasis of Ovarian Cancer SKOV3 Cells. Br J Cancer. 2017 Oct 10;117(8):1192-1201.
HLI373 is an efficacious Hdm2 inhibitor. HLI373 inhibits the ubiquitin ligase activity of Hdm2. HLI373 is effective in inducing apoptosis of several tumor cells that are sensitive to DNA-damaging agents[1]. Antimalarial activity[2].
IC50 & Target
Hdm2[1]; Apoptosis[1]; Antimalarial[2]
体外研究 (In Vitro)
HLI373 (3-15 μM; 15 hours) selectively kills tumor cells harboring wild type p53[1]. HLI373 (10-50 μM) stabilizes cellular Hdm2 in a dose-dependent manner. HLI373 (3 μM) activates p53 transcription[1]. HLI373 selectively inhibits auto-ubiquitylation of Hdm2[1]. Co-transfection with plasmids encoding p53 and Hdm2 results in degradation of p53. Incubation with HLI373 (5-10 μM; 8 hours) blocks p53 degradation. HLI373 increases p53 and Hdm2 protein levels in cells[1]. HLI 373 also shows lower IC50 values (below 6 μM) against both chloroquine-sensitive P. falciparum D6 strain (PfD6) and chloroquine-resistant P. falciparum W2 strain (PfW2) and exhibits early growth inhibition[2]. HLI-373 is a MDM2 inhibitor interrupting its ubiquitin E3 ligase activity, could abolish the ubiquitylation of its substrate protein p53. HLI-373 targets the C-terminus functioning as an E3 ubiquitin ligase[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.
Cell Viability Assay[1]
Cell Line:
Wild type p53 mouse embryo fibroblasts (MEFs), and p53-deficient MEFs
Concentration:
3, 10, 15 μM
Incubation Time:
15 hours
Result:
Increased cell death in wild type p53 MEFs in a dose-dependent manner, p53-deficient MEFs were relatively resistant.
Western Blot Analysis[1]
Cell Line:
U2OS cells
Concentration:
5, 10 μM
Incubation Time:
8 hours
Result:
Blocked p53 degradation caused by co-transfection with plasmids encoding p53 and Hdm2.
分子量
341.41
Formula
C18H23N5O2
CAS 号
502137-98-6
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]. Jirouta Kitagaki, et al. Targeting Tumor Cells Expressing p53 With a Water-Soluble Inhibitor of Hdm2. Mol Cancer Ther. 2008 Aug;7(8):2445-54.
[2]. Jagrati Jain, et al. Inhibitors of Ubiquitin E3 Ligase as Potential New Antimalarial Drug Leads. BMC Pharmacol Toxicol. 2017 Jun 2;18(1):40.
[3]. Ying Chen, et al. MDM2 Promotes Epithelial-Mesenchymal Transition and Metastasis of Ovarian Cancer SKOV3 Cells. Br J Cancer. 2017 Oct 10;117(8):1192-1201.
HLI373 is an efficacious Hdm2 inhibitor. HLI373 inhibits the ubiquitin ligase activity of Hdm2. HLI373 is effective in inducing apoptosis of several tumor cells that are sensitive to DNA-damaging agents[1]. Antimalarial activity[2].
IC50 & Target
Hdm2[1]; Apoptosis[1]; Antimalarial[2]
体外研究 (In Vitro)
HLI373 (3-15 μM; 15 hours) selectively kills tumor cells harboring wild type p53[1]. HLI373 (10-50 μM) stabilizes cellular Hdm2 in a dose-dependent manner. HLI373 (3 μM) activates p53 transcription[1]. HLI373 selectively inhibits auto-ubiquitylation of Hdm2[1]. Co-transfection with plasmids encoding p53 and Hdm2 results in degradation of p53. Incubation with HLI373 (5-10 μM; 8 hours) blocks p53 degradation. HLI373 increases p53 and Hdm2 protein levels in cells[1]. HLI 373 also shows lower IC50 values (below 6 μM) against both chloroquine-sensitive P. falciparum D6 strain (PfD6) and chloroquine-resistant P. falciparum W2 strain (PfW2) and exhibits early growth inhibition[2]. HLI-373 is a MDM2 inhibitor interrupting its ubiquitin E3 ligase activity, could abolish the ubiquitylation of its substrate protein p53. HLI-373 targets the C-terminus functioning as an E3 ubiquitin ligase[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
Wild type p53 mouse embryo fibroblasts (MEFs), and p53-deficient MEFs
Concentration:
3, 10, 15 μM
Incubation Time:
15 hours
Result:
Increased cell death in wild type p53 MEFs in a dose-dependent manner, p53-deficient MEFs were relatively resistant.
Western Blot Analysis[1]
Cell Line:
U2OS cells
Concentration:
5, 10 μM
Incubation Time:
8 hours
Result:
Blocked p53 degradation caused by co-transfection with plasmids encoding p53 and Hdm2.
分子量
341.41
Formula
C18H23N5O2
CAS 号
502137-98-6
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]. Jirouta Kitagaki, et al. Targeting Tumor Cells Expressing p53 With a Water-Soluble Inhibitor of Hdm2. Mol Cancer Ther. 2008 Aug;7(8):2445-54.
[2]. Jagrati Jain, et al. Inhibitors of Ubiquitin E3 Ligase as Potential New Antimalarial Drug Leads. BMC Pharmacol Toxicol. 2017 Jun 2;18(1):40.
[3]. Ying Chen, et al. MDM2 Promotes Epithelial-Mesenchymal Transition and Metastasis of Ovarian Cancer SKOV3 Cells. Br J Cancer. 2017 Oct 10;117(8):1192-1201.
