PARP-1 Selective Inhibitor Development

Poly(ADP-ribose) polymerase-1 (PARP-1) plays a critical role in the DNA damage repair pathway, particularly in the repair of single-strand breaks (SSBs). At Alfa Cytology, we specialize in the development of selective PARP-1 inhibitors, leveraging our extensive expertise in medicinal chemistry and preclinical research.

Introduction to PARP-1 Selective Inhibitor

PARP-1 facilitates the base excision repair (BER) process, which is essential for maintaining genomic integrity. Inhibitors targeting PARP-1 have emerged as a promising therapeutic strategy, particularly in the treatment of cancers with defective DNA repair mechanisms. The development of selective PARP-1 inhibitors aims to exploit the therapeutic window provided by these inhibitors while minimizing off-target effects that result from inhibition of PARP-2, which is vital for stem cell survival.

Fig. 1 The PARP family of enzymes and their reported functions. (Ngoi N. Y. L., et al. 2021)

The necessity for selective PARP-1 inhibitors stems from the dual roles of PARP-1 and PARP-2 in cellular processes. While PARP-1 is predominantly responsible for the repair of SSBs, PARP-2 is involved in maintaining stem cell function and genomic stability. Consequently, dual inhibition can lead to significant hematological toxicities, limiting the clinical utility of currently approved PARP inhibitors. This highlights the importance of developing compounds that selectively inhibit PARP-1 without affecting PARP-2.

PARP-1 Selective Inhibitor Development

Recent advancements in the design of selective PARP-1 inhibitors have focused on structure-activity relationships (SAR) and molecular simulations. Compounds such as AZD5305 and AZD9574 are examples of highly selective PARP-1 inhibitors currently undergoing clinical trials. The design of these inhibitors often involves modifications that enhance binding affinity to the catalytic domain of PARP-1 while avoiding the conserved regions that overlap with PARP-2.

Ongoing Clinical Trials Investigating PARP1 Selective Inhibitors:

Our Services

At Alfa Cytology, we specialize in the development of selective PARP-1 inhibitors, leveraging our extensive expertise in medicinal chemistry and preclinical research. Our services encompass a comprehensive range of activities, including:

Selective PARP-1 Inhibitor Development

• Target Validation
• Hit Identification
• Hit-to-Lead Service
• Lead Optimization Service

Modeling Services

• Cell Line Development
• Animal Models
• Organoid Models

Preclinical Studies

• Efficacy Studies
• Pharmacokinetic (PK) Studies
• Safety and Toxicology Studies
• Mechanistic Studies

PARP-1 inhibitors are primarily used for the treatment of several types of cancer, particularly those associated with defects in DNA repair mechanisms.

Alfa Cytology is committed to advancing the development of selective PARP-1 inhibitors through comprehensive modeling services. Our expertise and innovative approaches will help guide your projects from concept to clinical application. For inquiries regarding our services or to discuss potential collaborations in the development of selective PARP-1 inhibitors, please don't hesitate to contact us.

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