siremadlin

p53-MDM2 inhibitor

Also Known As:

HDM-201; HDM201; 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)-

Networked: 14 relevant articles (0 outcomes, 4 trials/studies)

Bio-Agent Context: Research Results

Heterocyclic Compounds: 198
- 1-Ring Heterocyclic Compounds
  - Azoles: 2138
    - Pyrroles: 369
      - siremadlin: 14
    - Imidazoles: 150
      - siremadlin: 14
  - Pyrimidines: 510
    - siremadlin: 14

Experts

1.	Fabre, Claire: 4 articles (03/2022 - 01/2021)
2.	Ferretti, Stephane: 4 articles (03/2022 - 01/2017)
3.	Guerreiro, Nelson: 4 articles (03/2022 - 11/2018)
4.	Halilovic, Ensar: 4 articles (03/2022 - 11/2018)
5.	Jullion, Astrid: 3 articles (01/2022 - 11/2018)
6.	Lunec, John: 3 articles (07/2021 - 01/2018)
7.	Wu, Chiao-En: 3 articles (07/2021 - 01/2018)
8.	Bauer, Sebastian: 2 articles (03/2022 - 01/2022)
9.	Lin, Chia-Chi: 2 articles (03/2022 - 01/2022)
10.	Meille, Christophe: 2 articles (03/2022 - 01/2021)

Related Diseases

1.	Neoplasms (Cancer) 03/01/2022 - "This phase I, dose-escalation study investigated the recommended dose for expansion (RDE) of siremadlin, a p53-MDM2 inhibitor, in patients with wild-type TP53 advanced solid or hematologic cancers. " 11/01/2018 - ": Pulsed high doses versus sustained low doses of the p53-MDM2 inhibitor HDM201 elicit a proapoptotic response from wild-type p53 cancer cells, offering guidance to current clinical trials with this and other drugs that exploit the activity of p53. " 01/01/2021 - "Combining HDM201 with PD-1 or PD-L1 blockade increased the number of complete tumor regressions. " 01/01/2021 - "Furthermore, HDM201 increased the percentage of Tbet+Eomes+ CD8+ T cells and the CD8+/Treg ratio within the tumor. " 01/01/2021 - "To investigate the role of p53 in controlling tumor-immune cell cross-talk, we studied murine syngeneic models treated with HDM201, a potent and selective second-generation MDM2 inhibitor. "
2.	Melanoma (Melanoma, Malignant) 01/23/2023 - "This approach based on in vitro/in vivo extrapolation may help in the design of potential clinical trials using siremadlin and trametinib and provide a rationale for their use in patients with melanoma." 01/23/2023 - "We performed physiologically based pharmacokinetic-pharmacodynamic (PBPK/PD) modelling and virtual clinical trial simulations for siremadlin, trametinib, and their combination in a virtual representation of melanoma patients. " 10/26/2022 - "The cytotoxicity of the Siremadlin and Trametinib combination was evaluated in vitro in melanoma A375 cells with MTS and RealTime-Glo assays. " 10/08/2022 - "We performed PBPK/PD modelling for siremadlin, trametinib, and their combination at various dose levels and dosing schedules in an A375 xenografted mouse model (melanoma cells). " 10/26/2022 - "Translation of the synergy between the Siremadlin (MDM2 inhibitor) and Trametinib (MEK inhibitor) combination observed in vitro into in vivo synergistic efficacy in melanoma requires estimation of the interaction between these molecules at the pharmacokinetic (PK) and pharmacodynamic (PD) levels. "
3.	Leukemia 03/01/2022 - "Results from a First-in-Human Phase I Study of Siremadlin (HDM201) in Patients with Advanced Wild-Type TP53 Solid Tumors and Acute Leukemia." 11/12/2019 - "Here, we assessed the MCL1-antagonist S63845, the MDM2-inhibitor HDM201, and the MEK1/2-inhibitor trametinib as single agents and in combination in a variety of AML cell lines and mononuclear cells isolated from patients with hematological malignancies centered on myeloid leukemia, some lymphatic leukemia, as well as some lymphomas, for their ability to induce apoptosis and cell death. "
4.	Disease Progression 01/01/2022 - "In this proof-of-concept, phase Ib, dose-escalation study, patients received siremadlin and ribociclib across different regimens until unacceptable toxicity, disease progression, and/or treatment discontinuation: Regimen A [4-week cycle: siremadlin once daily (QD) and ribociclib QD (2 weeks on, 2 weeks off)], Regimen B [3-week cycle: siremadlin once every 3 weeks; ribociclib QD (2 weeks on, 1 week off)], and Regimen C [4-week cycle: siremadlin once every 4 weeks; ribociclib QD (2 weeks on, 2 weeks off)]. "
5.	Liposarcoma 01/01/2022 - "Co-Targeting of MDM2 and CDK4/6 with Siremadlin and Ribociclib for the Treatment of Patients with Well-Differentiated or Dedifferentiated Liposarcoma: Results from a Proof-of-Concept, Phase Ib Study."

Related Drugs and Biologics

1.	siremadlin
2.	trametinib
3.	ribociclib
4.	RG7388
5.	Mitogen-Activated Protein Kinase Kinases (MEKs)
6.	GSK2830371
7.	nutlin 3
8.	Phosphoric Monoester Hydrolases (Phosphatases)
9.	Antineoplastic Agents (Antineoplastics)
10.	Immune Checkpoint Inhibitors

Related Therapies and Procedures

1.	Regimen B
2.	Therapeutics