MK-8745 / Merck (MSD) - LARVOL DELTA

Developing epigenetic synergistic drug combinations with albendazole in paediatric acute myeloid leukaemia (ASH 2025) - "Similar anthelmintic agents, mebendazole (MBZ) and parbendazole (PBZ), have been reported to have effects on epigenetic regulators that alter C-MYB degradation (Walf-Vorderwülbecke et al...These epigenetic hits represent various target families such as HDAC inhibitors (vorinostat, panobinostat, and CUDC-101), BET inhibitors (OTX-015, PFI-1, and (-)-JQ), aurora kinase inhibitors (MK-8745 and JNJ-7706621), and DNA synthesis inhibitors (cytarabine)...HDAC inhibitors (vorinostat), BET inhibitors (OTX-015) and histone methyltransferase (MS023) were among the most represented epigenetic target families, indicating potential mechanism of action of the novel ABZ+epigenetic combination. The novel drug candidate ABZ was found to have remarkable anti-leukaemia efficacy in murine and human models of childhood AML in vitro and in vivo while having negligible effects in normal cells. Current work is focused on evaluating ABZ+epigenetic synergistic combinations that will be taken..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics • HOXA9 • IL1B • MEIS1

Targeting aurora kinase a (AURKA) in cancer: molecular docking and dynamic simulations of potential AURKA inhibitors. (PubMed, Med Oncol) - "Furthermore, MK8745 analogues are potential replacements for MK8745 because they have strong binding affinity, which is consistent with MDS results, and have appropriate ADMET properties. Through basic, clinical, and preclinical research, the identification of novel compounds may open the door for their prospective use in the prevention of cancer."

Journal • Oncology

AML-377 A "Designed" High-Throughput Drug Screening Strategy Identifies Aurora Kinase A Inhibitors as Promising Preclinical Candidates for the Treatment of NPM1-Mutated AML. (PubMed, Clin Lymphoma Myeloma Leuk) - "We demonstrated that using HTS can considerably shorten drug discovery time scales, leading to the identification of promising lead compounds. Our study is the first to provide preclinical evidence of the antileukemic activity of AURKAi, with particular focus on NPM1-mutated AML."

Journal • Preclinical • Acute Myelogenous Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • Psychiatry • AURKA • NPM1

A “Designed” High-Throughput Drug Screening Strategy Identifi es Aurora Kinase A Inhibitors as Promising Preclinical Candidates for the Treatment of NPM1-Mutated AML (SOHO 2022) - "In the validation assay, 2 compounds (MK-5108 and MK-8745) were confi rmed as more active against NPM1-mutated than NPM1–wild-type AML cells by either CyQUANT or apoptosis assay. Strikingly, we confi rmed selectivity for two additional AURKAi (Alisertib and ENMD-2076, both isoform-selective inhibitors of AURKA) that were not included in the screening library... We demonstrated that using HTS can considerably shorten drug discovery time scales, leading to the identifi cation of promising lead compounds. Our study is the fi rst to provide preclinical evidence of the antileukemic activity of AURKAi, with particular focus on NPM1-mutated AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AURKA • NPM1

Apoptosis is responsible for the cytotoxic effects of anti-GD2 ganglioside antibodies and aurora A kinase inhibitors on human neuroblastoma cells. (PubMed, Acta Biochim Pol) - "However, the presence of necroptosis was ruled out in MK-5108-treated IMR-32 and CHP-134 cells. In summary, the effects of the combination of ch14.18/CHO mAb and aurora A kinase inhibitors (MK-5108 and MK-8745) were shown to enhance apoptosis in IMR-32 cells compared to when used individually."

IO biomarker • Journal • Neuroblastoma • Oncology • Solid Tumor • AURKA • CASP3 • CASP7

Macrophomina vaccinii Causes a Basal Stem and Root Rot of Patchouli (Pogostemon cablin) in China. (PubMed, Plant Dis) - "BLASTn searches revealed that 100% identity with the existing sequences of ex-type culture CGMCC3.19503 of Macrophomina vaccinii (ITS, MK687450; EF-1α, MK687426; and TUB, MK687434), respectively. 2019). To our knowledge, this is the first report of M. vaccinii causing basal stem and root rot on patchouli in China and worldwide."

Journal • Dyspepsia • Pain