| Name | Siremadlin |
| Description | Siremadlin (NVP-HDM 201) is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor. |
| In vitro | Siremadlin inhibits both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation[1] |
| In vivo | 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[1]. Siremadlin has recently entered Phase 1 clinical trials in cancer patients[2]. 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]. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (3.6 mM), Sonication is recommended.
DMSO : 56.75 mg/mL (102.18 mM), Sonication is recommended.
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| Keywords | Ubiquitin ligase | Ubiquitin conjugating enzyme | Ubiquitin activating enzyme | Siremadlin | p53-MDM2 | NVP-HDM-201 | NVP-HDM201 | MDM-2/p53 | Inhibitor | inhibit | HDM-201 | HDM201 | HDM 201 | E3Enzyme | E3 ligating enzyme | E3 Enzyme | E2Enzyme | E2 Enzyme | E2 conjugating enzyme | E1Enzyme | E1/E2/E3 Enzyme | E1 Enzyme | E1 activating enzyme |
| Inhibitors Related | 10-Hydroxydecanoic Acid | Flubendazole | Diuron | Gallium maltolate | Yucasin | D-(-)-3-Phosphoglyceric acid disodium | EN219 | Thiabendazole | Triglycidyl isocyanurate | Indole-3-carbinol | Methyl methanesulfonate | (E/Z)-10-Hydroxy-2-decenoic acid |
| Related Compound Libraries | Anti-Colorectal Cancer Compound Library | Bioactive Compound Library | HIF-1 Signaling Pathway Compound Library | ReFRAME Related Library | Anti-Cancer Metabolism Compound Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | Inhibitor Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Cancer Active Compound Library | Anti-Cancer Drug Library |
United States
