CYC116 / Cyclacel - LARVOL DELTA

Loss of heterozygosity of CYP2D6 enhances the sensitivity of hepatocellular carcinomas to talazoparib. (PubMed, EBioMedicine) - "Exploiting the loss of drug-metabolizing enzyme gene activity in tumor cells following loss of heterozygosity could present a promising therapeutic strategy for targeted cancer treatment."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Identification and structural characterization of small molecule inhibitors of PINK1. (PubMed, Sci Rep) - "The crystal structures of insect PINK1 bound to PRT062607 or CYC116 reveal how the compounds interact with the ATP-binding pocket. PRT062607 notably engages with the catalytic aspartate and causes a destabilization of insert-2 at the autophosphorylation dimer interface. While PRT062607 is not selective for PINK1, it provides a scaffold for the development of more selective and potent inhibitors of PINK1 that could be used as chemical probes."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation • SYK

The Aurora Kinase Inhibitor CYC116 Promotes the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells. (PubMed, Mol Cells) - "In addition, a number of other Aurora kinase inhibitors have also been found to promote the maturation of hPSC-CMs. Our data suggest that blocking aurora kinase activity and regulating cell cycle progression may promote the maturation of hPSC-CMs."

Journal • Heart Failure • AURKA

A Phase I Pharmacologic Study of CYC116, an Oral Aurora Kinase Inhibitor, in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=25; Terminated; Sponsor: Cyclacel Pharmaceuticals, Inc.; N=40 ➔ 25

Clinical • Enrollment change • Oncology • Solid Tumor

Cyclacel announces presentation of preclinical data demonstrating combination potential of clinical agents at AACR annual meeting (Globe Newswire) -

Resistant clones generated were cross-resistant to other Aurora kinase inhibitors tested, but showed differing resistance or sensitivity to a panel of other chemotherapeutics; Unlike ZM447439-resistant clones, CYC116-resistant clones did not contain mutations in the Aurora kinase genes, but became stably tetraploid; CYC116-resistant clones with functional p53 showed increased sensitivity to navitoclax

Oncology