NVP-HDM201
Names
[ CAS No. ]:
1448867-41-1
[ Name ]:
NVP-HDM201
[Synonym ]:
(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
Biological Activity
[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]
[Related Small Molecules]
Chemical & Physical Properties
[ 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℃