HDM-201

CAS No. 1448867-41-1

HDM-201( NVP-HDM 201 | NVP HDM201 | Siremadlin )

Catalog No. M11927 CAS No. 1448867-41-1

HDM-201 (NVP-HDM 201, Siremadlin)?is a highly potent p53-MDM2 interaction inhibitor with biochemical IC50 of 0.13 nM, cellular IC50 of 90 nM.

Purity : >98% (HPLC)

COA Datasheet HNMR HPLC MSDS Handing Instructions
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Biological Information

  • Product Name
    HDM-201
  • Note
    Research use only, not for human use.
  • Brief Description
    HDM-201 (NVP-HDM 201, Siremadlin)?is a highly potent p53-MDM2 interaction inhibitor with biochemical IC50 of 0.13 nM, cellular IC50 of 90 nM.
  • Description
    HDM-201 (NVP-HDM 201, Siremadlin)?is a highly potent p53-MDM2 interaction inhibitor with biochemical IC50 of 0.13 nM, cellular IC50 of 90 nM; a second generation p53-MDM2 inhibitor that recently entered phase I clinical trial.
  • In Vitro
    Siremadlin (NVP-HDM201) disrupts both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation.
  • 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. 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. 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.
  • Synonyms
    NVP-HDM 201 | NVP HDM201 | Siremadlin
  • Pathway
    Apoptosis
  • Target
    MDM2-p53
  • Recptor
    MDM2-p53
  • Research Area
    ——
  • Indication
    ——

Chemical Information

  • CAS Number
    1448867-41-1
  • Formula Weight
    555.4125
  • Molecular Formula
    C26H24Cl2N6O4
  • Purity
    >98% (HPLC)
  • Solubility
    DMSO : ≥ 56.75 mg/mL 102.18 mM
  • SMILES
    O=C1N(C2=CC(Cl)=CN(C)C2=O)[C@@H](C3=CC=C(Cl)C=C3)C4=C1N=C(C5=CN=C(OC)N=C5OC)N4C(C)C
  • 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

Shipping & Storage Information

  • Storage
    (-20℃)
  • Shipping
    With Ice Pack
  • Stability
    ≥ 2 years

Reference

1. Furet P, et al. Bioorg Med Chem Lett. 2016 Oct 1;26(19):4837-41. 2. Chapeau EA, et al. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3151-3156.
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