- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, alrizomadlin (APG-115) / Ascentage Pharma
Journal, IO biomarker: MDM2 inhibitor APG-115 synergizes with ABT-199 to induce cell apoptosis in chronic lymphocytic leukemia. (Pubmed Central) - Aug 15, 2024 Collectively, this study demonstrates that APG-115 activates p53 and thus inhibits multiple pro-survival mechanisms, which provides a rational explanation for APG-115 efficiency in inducing cell apoptosis in CLL. The synergistic effect of APG-115 with ABT-199 suggested a potential combination application in CLL therapy.
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma
Journal: Unveiling therapeutic prospects: targeting MDM-2 in non-muscle invasive bladder cancer. (Pubmed Central) - Mar 18, 2024 Analysis of five trajectories, including RMSD, RMSF, hydrogen bond, radius of gyration, coulomb short-range electrostatic spectra, and free binding energy, confirmed that Mol-126 exhibited the highest structural stability compared to the reference drug (Alrizomadlin). Notably, Mol-126 is a derivative of 3-phenoxypropionic acid, which shows promise for the development of alternative therapeutic treatments for non-responsive bladder cancer patients.Communicated by Ramaswamy H. Sarma.
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma
Trial suspension: CAPS: APG-115 in Salivary Gland Cancer Trial (clinicaltrials.gov) - Mar 2, 2024 P1/2, N=34, Suspended, The findings provide a scientific rationale for future clinical development of APG-5918 and alrizomadlin for PCa patients. Recruiting --> Suspended
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma, lisaftoclax (APG-2575) / Ascentage Pharma
Phase classification, Trial completion date, Trial primary completion date, Combination therapy: A Study Evaluating APG-115 as a Single Agent or in Combination With APG-2575 in Subjects With T-PLL (clinicaltrials.gov) - Nov 28, 2023 P2, N=36, Recruiting, This is the first study to evaluate the activity of MDM2 inhibition in patients with SGC. Phase classification: P2a --> P2 | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2023 --> May 2024
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma, Yervoy (ipilimumab) / Ono Pharma, BMS
CCT6A and triple-negative breast cancer metastasis: Activating the AKT/MDM2/P53 pathway. () - Apr 26, 2023 - Abstract #ASCO2023ASCO_4307; Our research demonstrated that CCT6A can enhance metastasis of triple-negative breast cancer via up-regulating the AKT/MDM2/P53 pathway. These results provide rationales for MDM2 inhibitor combined with anti-CTLA-4 antibody for preventing TNBC metastasis.
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma
MDM2 inhibitor alrizomadlin (APG-115) stabilizes p53 and synergizes with proteasome inhibitors in multiple myeloma (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_6900; In vivo studies showed that coadministration of alrizomadlin with proteasome inhibitor bortezomib or carfilzomib enhanced tumor regression (vs. single agents) in H929 xenograft models...In conclusion, our results demonstrate that the combination of MDM2 inhibitor APG-115 and proteasome inhibitors have synergistic antitumor effects on MM tumors harboring WT TP53. These data lay a foundation for clinical trials of a new and novel therapeutic option for patients with refractory MM.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, alrizomadlin (APG-115) / Ascentage Pharma, lisaftoclax (APG-2575) / Ascentage Pharma
Co-targeting MDM2-p53 and BCL-2 apoptosis pathways overcomes resistance conferred by acquired BCL-2 gene mutations in preclinical models (Section 23) - Mar 9, 2022 - Abstract #AACR2022AACR_5914; Further, lisaftoclax plus alrizomadlin more effectively blocked cell cycle entry into the G2/M phase, resulting in accumulation of sub-G1 apoptotic cells. In summary, our study demonstrates, for the first time, that co-targeting BCL-2 and MDM2-p53 apoptosis pathways overcame resistance to BCL-2 inhibitors conferred by acquired BCL-2 gene mutations, potentially offering a viable strategy to overcome drug resistance and thus providing a rationale for clinical investigation.
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma, navtemadlin (KRT-232) / Kartos Therap, serdemetan (JNJ-26854165) / J&J
MDM2 inhibition as a non-hormone dependent radiosensitizing strategy in p53 wild-type breast cancer models (Section 10) - Mar 9, 2022 - Abstract #AACR2022AACR_3067; An MDM2 inhibitor (JNJ-26854165) was nominated as an effective drug in treatment for RT-resistant BC cell lines (R2 = 0.43, p value 10μm)... These results demonstrate the combination of RT and MDM2 inhibition may be an effective therapeutic strategy in patients with p53-wild type breast cancer, regardless of hormone receptor status.
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma
Trial completion date, Trial primary completion date, Combination therapy: A Study of APG-115 Alone or Combined With Azacitidine in Patients With AML, CMML, or MDS (clinicaltrials.gov) - Feb 10, 2022 P1/2, N=69, Recruiting, These results demonstrate the combination of RT and MDM2 inhibition may be an effective therapeutic strategy in patients with p53-wild type breast cancer, regardless of hormone receptor status. Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
Co-Targeting Intrinsic and Extrinsic Apoptosis to Maximize Cell Death Induction in Venetoclax-Resistant AML Cells (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5010; Only in the triple combination group, cIAP1, cIAP2, and XIAP as well as MDM2 were largely diminished and p21 was marked decreased. In conclusion, our study demonstrates that co-targeting intrinsic and extrinsic apoptosis maximizes cell death induction in AML cells with acquired resistance to VEN or with TP53 deletion/mutations by antagonizing Bcl-2, eliminating cIAPs and XIAP, as well as MDM2 and p21, a finding that needs to be validated clinically.
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma
Enrollment change, Trial completion date, Trial primary completion date: CAPS: APG-115 in Salivary Gland Cancer Trial (clinicaltrials.gov) - Oct 29, 2021 P1/2, N=34, Recruiting, In conclusion, our study demonstrates that co-targeting intrinsic and extrinsic apoptosis maximizes cell death induction in AML cells with acquired resistance to VEN or with TP53 deletion/mutations by antagonizing Bcl-2, eliminating cIAPs and XIAP, as well as MDM2 and p21, a finding that needs to be validated clinically. N=62 --> 34 | Trial completion date: Dec 2022 --> Jan 2025 | Trial primary completion date: Sep 2022 --> Jul 2024
- |||||||||| alrizomadlin (APG-115) / Ascentage Pharma
Journal: The ubiquitin ligase MDM2 sustains STAT5 stability to control T cell-mediated antitumor immunity. (Pubmed Central) - Jun 30, 2021 Targeting the p53-MDM2 interaction with a pharmacological agent, APG-115, augmented MDM2 in T cells, thereby stabilizing STAT5, boosting T cell immunity and synergizing with cancer immunotherapy...Clinically, MDM2 abundance correlated with T cell function and interferon-γ signature in patients with cancer. Thus, the p53-MDM2 pathway controls T cell immunity, and targeting this pathway may treat patients with cancer regardless of tumor p53 status.
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