Name | HDM201 |
---|---|
Synonyms |
(6S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-3-pyridinyl)-6-(4-chlorophenyl)-2-(2,4-dimethoxy-5-pyrimidinyl)-1-isopropyl-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one
Pyrrolo[3,4-d]imidazol-4(1H)-one, 5-(5-chloro-1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-6-(4-chlorophenyl)-2-(2,4-dimethoxy-5-pyrimidinyl)-5,6-dihydro-1-(1-methylethyl)-, (6S)- NVP-HDM201 |
Description | NVP-HDM201 (HDM201) is a potent and highly specific MDM-2/p53 inhibitor currently under phase I clinical trial. |
---|---|
Related Catalog | |
In Vitro | NVP-HDM201 disrupts both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation[1]. |
In Vivo | 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 NVP-HDM201. Sixteen out of 21 allograft models are sensitive to NVP-HDM201 but ultimately relapse under treatment. A comparison of tumors with acquired resistance to NVP-HDM201 and untreated tumors identified 87 genes that are differentially and significantly targeted by the PB transposon[1]. 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 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 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]. |
References |
Density | 1.5±0.1 g/cm3 |
---|---|
Boiling Point | 736.5±70.0 °C at 760 mmHg |
Molecular Formula | C26H24Cl2N6O4 |
Molecular Weight | 555.413 |
Flash Point | 399.2±35.7 °C |
Exact Mass | 554.123596 |
LogP | 2.01 |
Vapour Pressure | 0.0±2.4 mmHg at 25°C |
Index of Refraction | 1.688 |
Storage condition | -20℃ |