PARP-7 Selective Inhibitor Development

Poly(ADP-ribose) polymerase 7 (PARP-7), known for its role in regulating immune responses, has emerged as a critical target in cancer therapy. At Alfa Cytology, we specialize in the development of selective PARP-7 inhibitors, leveraging our extensive expertise in medicinal chemistry and preclinical research.

Introduction to PARP-7 Selective Inhibitor

Overexpression of PARP-7 in various tumors correlates with immune suppression and poor patient outcomes. Inhibiting PARP-7 can restore type I interferon (IFN) signaling, enhancing the innate immune response and potentially leading to improved antitumor efficacy.

Fig. 1 Selective PARP7 Inhibitor. (Gu H., et al. 2024)

The mechanism of action of PARP-7 inhibitors hinges on their ability to enhance immune signaling pathways. By inhibiting PARP-7, these compounds facilitate the recovery of type I IFN signaling, promoting T-cell infiltration into tumors and activating immune responses against cancer cells. This dual mechanism of action underscores the potential of PARP-7 inhibitors in novel immunotherapeutic strategies, particularly in combination with existing therapies.

PARP-7 Selective Inhibitor Development

Recent advancements have highlighted selective PARP-7 inhibitors, such as compound I-1, which exhibit high potency and specificity. With an IC50 of 7.6 nM, I-1 demonstrates not only effective inhibition of PARP-7 but also minimal effects on other PARP family members, crucial for reducing unwanted side effects in therapeutic applications.

Compound	Structure	Effect
(S)-XY-05		Regulating nucleic acid-sensing and IFN-β signaling Strong tumor suppressor activity

Our Services

At Alfa Cytology, we provide comprehensive preclinical development services tailored to support the advancement of PARP-7 selective inhibitors. Our offerings include:

Drug Discovery and Design

Our team leverages advanced computational techniques and structural biology to design and optimize PARP-7 inhibitors. Utilizing molecular docking simulations, we analyze binding interactions to enhance selectivity and potency.

Structure-Based Drug Design
Fragment-Based Drug Discovery

In Silico Modeling
SAR (Structure-Activity Relationship) Studies

In Vitro and In Vivo Efficacy Evaluation

We conduct rigorous in vitro assays to assess the efficacy of PARP-7 inhibitors against various cancer cell lines. Our methodologies include MTT assays and cell viability studies, providing critical data on antiproliferative effects and cytotoxicity. Additionally, we utilize syngeneic mouse models for in vivo evaluations, allowing us to assess tumor growth inhibition and immune modulation in a physiological context.

Pharmacokinetic Studies

Understanding the pharmacokinetic profile of PARP-7 inhibitors is essential for their clinical success. Alfa Cytology performs comprehensive pharmacokinetic studies, analyzing absorption, distribution, metabolism, and excretion (ADME) parameters. This data informs dosing strategies and helps optimize the therapeutic index of candidate compounds.

Safety Assessment

We provide a comprehensive safety assessment that helps clients effectively identify potential toxicities, side effects, and overall risks before clinical trials.

Dose-Response Studies
Preclinical Toxicology Studies

Long-Term Toxicity Studies
Genotoxicity and Carcinogenicity Testing

For more information regarding our preclinical services in PARP-7 selective inhibitor development or to explore potential collaborations, please contact Alfa Cytology. Our dedicated team of experts is committed to advancing cancer research through innovative therapeutic solutions.

Reference

Gu H., Yan W., and et al. Discovery of Highly Selective PARP7 Inhibitors with a Novel Scaffold for Cancer Immunotherapy. J Med Chem. 2024, 67(3): 1932-1948.

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