Siremadlin
Siremadlin Basic information
- Product Name:
- Siremadlin
- Synonyms:
-
- (6S)-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)-Pyrrolo[3,4-d]imidazol-4(1H)-one
- HDM-201
- NVP-HDM201
- CS-2613
- CS-2787
- HDM201; HDM 201; HDM-201; NVP-HDM201; NVP-HDM-201; NVP-HDM 201
- (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
- Siremadlin
- CAS:
- 1448867-41-1
- MF:
- C26H24Cl2N6O4
- MW:
- 555.41
- Mol File:
- 1448867-41-1.mol
Siremadlin Chemical Properties
- Boiling point:
- 736.5±70.0 °C(Predicted)
- Density
- 1.47±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO : ≥ 56.75 mg/mL (102.18 mM)
- form
- Solid
- pka
- 1.33±0.29(Predicted)
- color
- White to off-white
- InChIKey
- AGBSXNCBIWWLHD-FQEVSTJZSA-N
- SMILES
- C1(C2=CN=C(OC)N=C2OC)=NC2C(=O)N(C3=CC(Cl)=CN(C)C3=O)[C@@H](C3=CC=C(Cl)C=C3)C=2N1C(C)C
Siremadlin Usage And Synthesis
Uses
Siremadlin is an oral biologic agent that is a selective inhibitor of the p53-MDM2 interaction and is being investigated for the treatment of patients with myeloid malignancies after showing single agent activity in preclinical studies. the safety profile of Siremadlin did not differ significantly between tumor types and treatment regimens.
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].
SiremadlinSupplier
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