MDM2 inhibitors are used in cancer treatment where human tumors express wild-type p53 and overexpression of the oncogene MDM2. MDM2 overexpression is common in 7 percent of all cancers. Cancers with these characteristics often have a poor prognosis, are chemo resistant, or are in advanced stage of the disease. The p53 gene is a tumor suppressor which is often inactivated by genetic mutations in cancer.
MDM2 is an important negative regulator of the p53 tumor suppressor, and the p53 protein is a regulator of the MDM2 expression. The p53 negative regulator murine double minute 2 (MDM2) can be inhibited as a treatment strategy to ensure the p53 gene tumor suppressor can do its job. The MDM2 protein is also known as the E3 ubiquitin ligase. When the MDM2 regulator can bind to p53, transcription cannot occur, allowing cancerous cells to grow.
Clinical Trials Using MDM2 Inhibitors
The treatment of cancer using MDM2 inhibitors is increasing in popularity, as one can see with the number of MDM2 inhibitors being researched in clinical trials. Clinical trials are using MDM2 inhibitors to treat cancers such as brain cancer, myelofibrosis, and leukemia. Types of MDM2 inhibitors include CGM097, AMG-232, HDM201, ALRN-6924, RG7112, RG7388, APG-115, BI-907828, and DS-3032b.
Clinical Trials using the MDM2 inhibitor AMG-232 include:
- Testing the Ability of AMG 232 (KRT 232) to Get into the Tumor in Patients with Brain Cancer
- ClinicalTrials.gov Identifier: NCT03107780
- An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined with Ruxolitinib in Patients with Primary Myelofibrosis, Post-Polycythemia Vera MF, or Post-Essential Thrombocythemia MF, Who Have a Suboptimal Response to Ruxolitinib
- ClinicalTrials.gov Identifier: NCT04485260
- Testing the Addition of an anti0cancer drug, KRT-232 (AMG 232), to the Usual Treatments in Patients with Acute Myeloid Leukemia
- ClinicalTrials.gov Identifier: NCT04190550
- Testing the Addition of KRT-232 (AMG 232) to Usual Chemotherapy for Relapsed Multiple Myeloma
- ClinicalTrials.gov Identifier: NCT03031730
- Safety and Efficacy of KRT-232 in Combination with Acalabrutinib in Subjects With R/R DLBCL or R/R CLL
- ClinicalTrials.gov Identifier: NCT04502394
- TL-895 and KRT-232 Study in Acute Myeloid Leukemia
- ClinicalTrials.gov Identifier: NCT04669067
- KRT-232 (AMG-232) and Decitabine in Treating Patients with Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia
- ClinicalTrials.gov Identifier: NCT03041688