KU-0060648 / Axon Medchem - LARVOL DELTA

Gene Expression-Based Drug Repurposing Predicted GSK-2126458 and KU-0060648 as Candidate Small Molecules for Glioblastoma Multiforme Treatment. (PubMed, Biotechnol Bioeng) - "It was identified that two FDA-approved drugs, GSK-2126458/Omipalisib (TF-IDF value = 0.019) and KU 0060648/trihydrochloride (TF-IDF value = 0) and vorinostat (TF-IDF value = 0.29), which is frequently studied in GBM may be promising candidates for GBM. GSK-2126458 drug molecule showed the lowest IC50 value with 0.40 µM and triggered necrosis with 26.6% PI positive cell labeling. Further in vitro and in vivo validation of both small molecules may provide new treatment options for GBM."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors. (PubMed, Int J Mol Sci) - "Combination of THZ531 with either DNA-PK inhibitor (KU-0060648) or PARP inhibitor (Olaparib) led to synergistic cell death. In addition, combination treatment of THZ531 with Olaparib significantly reduced tumor burden in animal models. Our findings suggest that using a CDK12 inhibitor in combination with other DNA repair inhibitors may establish an effective therapeutic regimen to benefit myeloma patients."

Journal • Synthetic lethality • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Development of a CRISPR-Cas9 based luciferase turn-on system as non-homologous end joining pathway reporter. (PubMed, Chembiochem) - "Different known chemical inhibitors of the NHEJ pathway, such as NU7441, KU0060648, and KU55933, could significantly inhibit the bioluminescent signal generated by CRISPR-Cas9 targeting. In addition, we validated our system by high throughput sequencing."

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PARP Inhibitor Olaparib Causes No Potentiation of the Bleomycin Effect in VERO Cells, Even in the Presence of Pooled ATM, DNA-PK, and LigIV Inhibitors. (PubMed, Int J Mol Sci) - "Poly(ADP-ribosyl)polymerase (PARP) synthesizes poly(ADP-ribose) (PAR), which is anchored to proteins. A VERO subpopulation was resistant to BLEO, BLEO + OLA, and BLEO + OLA + ATM inhibitor KU55933 + DNA-PK inhibitor KU-0060648 + LigIV inhibitor SCR7 pyrazine. Regarding the mechanism(s) behind the resistance and lack of synthetic lethality, some hypotheses have been discarded and alternative hypotheses are suggested."

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