HDM201
HDM201, also known as Siremadlin or NVP-HDM201, inhibits the Mdm2-p53 protein-protein interaction, with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs. Mdm4. It binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction of the Mdm2 and p53 proteins as well as leading to the activation of the p53 pathway. Currently, interfering the interaction between the tumor suppressor p53 and its main negative regulator MDM2 has become a therapeutic concept explored to treat cancers.
References:
1. Stachyra-Valat T, Baysang F, D’Alessandro AC, et al. Abstract 1239: NVP-HDM201: Biochemical and biophysical profile of a novel highly potent and selective PPI inhibitor of p53-Mdm2. Cancer Research, 2016, 76(14 Suppl): Abstract nr 1239.
2. Jeay S, Ferretti S, Holzer P, et al. Dose and Schedule Determine Distinct Molecular Mechanisms Underlying the Efficacy of the p53-MDM2 Inhibitor HDM201. Cancer Research, 2018, 78(21): 6257-6267.
| Storage | Store at -20°C |
| M.Wt | 555.41 |
| Cas No. | 1448867-41-1 |
| Formula | C26H24Cl2N6O4 |
| Synonyms | NVP-HDM201 |
| Solubility | insoluble in H2O; ≥49.1 mg/mL in DMSO; ≥51.8 mg/mL in EtOH |
| Chemical Name | (S)-5-(5-chloro-1-methyl-2-oxo-1,2-dihydropyridin-3-yl)-6-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-1-isopropyl-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one |
| SDF | Download SDF |
| Canonical SMILES | ClC1=CC=C([C@@H]2N(C3=CC(Cl)=CN(C)C3=O)C(C4=C2N(C(C)C)C(C5=C(OC)N=C(OC)N=C5)=N4)=O)C=C1 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[2] | |
|
Cell lines |
Human SJSA-1 cancer cells |
|
Reaction Conditions |
Continuous low-dose treatment: 1.5 μmol/L for 7 ~ 10 h; pulsed high-dose treatment: 0.1 μmol/L for 48 ~ 72 h |
|
Applications |
Continuous exposure of HDM201 resulted in induction of p21 and delayed accumulation of apoptotic cells. In contrast, high-dose pulses of HDM201 were associated with marked induction of PUMA and a rapid onset of apoptosis. |
| Animal experiment:[2] | |
|
Animal models |
SJSA-1 and HSAX2655 tumor-bearing rats |
|
Dosage form |
5 or 27 mg/kg Orally |
|
Applications |
HDM201 at 27 mg/kg induced robust increases in p21 and PUMA proteins whereas only p21 protein was increased after the low-dose treatment (5 mg/kg). Single high-dose treatment of HDM201 induced PUMA-associated tumor regression in vivo. |
|
Note |
The technical data provided above is for reference only. |
|
References: 1. Stachyra-Valat T, Baysang F, D’Alessandro AC, et al. Abstract 1239: NVP-HDM201: Biochemical and biophysical profile of a novel highly potent and selective PPI inhibitor of p53-Mdm2. Cancer Research, 2016, 76(14 Suppl): Abstract nr 1239. 2. Jeay S, Ferretti S, Holzer P, et al. Dose and Schedule Determine Distinct Molecular Mechanisms Underlying the Efficacy of the p53-MDM2 Inhibitor HDM201. Cancer Research, 2018, 78(21): 6257-6267. |
|
Quality Control & MSDS
- View current batch:
Chemical structure
