PARP-10 Selective Inhibitor Development

Poly (ADP-ribose) polymerase 10 (PARP-10) is emerging as a critical component in the regulation of DNA repair mechanisms, particularly in the context of single-stranded DNA (ssDNA) gaps formed during replication stress. At Alfa Cytology, we specialize in the development of selective PARP-10 inhibitors, leveraging our extensive expertise in medicinal chemistry and preclinical research.

Introduction to PARP-10 Selective Inhibitor

The role of PARP-10 in promoting genomic stability, especially in BRCA-deficient cells, positions it as a promising target for selective inhibitors. Recent studies indicate that PARP-10 interacts with RAD18, facilitating PCNA ubiquitination and the recruitment of translesion synthesis (TLS) polymerases, such as REV1. The dysregulation of these processes is implicated in various cancers, making PARP-10 an attractive target for therapeutic intervention.

Fig. 1 In cells with concomitant inactivation of BRCA and PARP10, ssDNA gaps are expanded by the MRE11 exonuclease, resulting in cytotoxicity. (Khatib J. B., et al. 2024)

PARP-10 Selective Inhibitor Development

Selective inhibitors of PARP-10 can potentially mitigate the accumulation of DNA damage in cancer cells, particularly those exhibiting BRCA mutations. The development of such inhibitors involves a thorough understanding of the molecular interactions and pathways mediated by PARP-10. By inhibiting its activity, it is possible to enhance the sensitivity of cancer cells to existing treatments, providing a dual approach to tackling malignancies.

Our Services

At Alfa Cytology, we specialize in the development and characterization of PARP-10 selective inhibitors. Our comprehensive services include:

Target Identification and Validation

Utilizing advanced screening techniques, we identify and validate potential small-molecule inhibitors of PARP-10. Our team employs high-throughput screening methods alongside in vitro assays to confirm the specificity and efficacy of candidate compounds.

Lead Optimization

Once potential inhibitors are identified, we focus on lead optimization to enhance their pharmacological properties. This process involves structure-activity relationship (SAR) studies, where we systematically modify chemical structures to improve potency, selectivity, and bioavailability.

Mechanistic Studies

Understanding the mechanism of action of PARP-10 inhibitors is crucial for their development. We conduct detailed biochemical assays to elucidate how these compounds interact with PARP-10 and affect downstream signaling pathways, including their impact on RAD18-mediated PCNA ubiquitination and TLS activity.

Preclinical Testing

Our preclinical CRO services include a robust framework for testing the efficacy and safety of PARP-10 inhibitors in various cancer models. We utilize both in vitro and in vivo models to evaluate therapeutic potential, allowing us to gather critical data for future clinical trials.

To learn more about our PARP-10 selective inhibitor development services or to discuss collaboration opportunities, please contact us at Alfa Cytology. Our team of experts is dedicated to advancing the field of targeted therapies, and we look forward to contributing to your research and development efforts.

For research use only. Not intended for any clinical use.