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Accelerating Pik3Ca Related Overgrowth Spectrum Drug Development

PIK3CA related overgrowth spectrum (PROS) presents significant therapeutic challenges due to its complex genetic basis and heterogeneous clinical manifestations. Protheragen is a specialized partner in the development of therapeutics targeting PROS, leveraging deep expertise in PIK3CA-driven pathologies. Protheragen offers a comprehensive suite of preclinical drug development solutions, encompassing target validation, lead optimization, pharmacology, and IND-enabling studies. With a team of experienced scientists and access to state-of-the-art platforms, Protheragen integrates advanced molecular biology, in vitro and in vivo modeling, and robust pharmacokinetic and toxicology assessment. Every stage of the development process is executed in alignment with the latest regulatory standards, ensuring data integrity and streamlined progression toward clinical evaluation. By combining scientific rigor with cutting-edge technologies, Protheragen is dedicated to accelerating the translation of innovative PROS therapeutics from discovery to the clinic. Protheragen’s commitment to excellence and partnership empowers clients to address the unmet needs of patients affected by PIK3CA-related disorders.

What is Pik3Ca Related Overgrowth SpectrumTargets for Pik3Ca Related Overgrowth SpectrumDrug Discovery and Development ServicesWhy Choose Us

What is Pik3Ca Related Overgrowth Spectrum

PIK3CA-Related Overgrowth Spectrum (PROS) encompasses a group of rare disorders caused by postzygotic, somatic activating mutations in the PIK3CA gene, which encodes the p110α subunit of phosphatidylinositol 3-kinase (PI3K). These mosaic mutations result in hyperactivation of the PI3K/AKT/mTOR signaling pathway, leading to abnormal cell growth, proliferation, and differentiation in affected tissues. The pathological process manifests as segmental, asymmetric overgrowth involving skin, subcutaneous tissue, muscle, bone, vasculature, and sometimes internal organs, with the severity and distribution varying widely among individuals. Clinically, PROS presents with a spectrum of manifestations, including congenital or progressive overgrowth, vascular and lymphatic malformations, epidermal anomalies, and, in some subtypes, neurological involvement such as seizures or developmental delay. Diagnosis relies on clinical assessment, imaging studies to delineate tissue involvement, and definitive identification of a somatic PIK3CA mutation through molecular genetic testing of affected tissue. Alpelisib, a selective PI3Kα inhibitor, is the first targeted therapy approved for PROS, offering symptomatic relief and reduction in overgrowth by directly inhibiting the underlying signaling pathway. Management also includes supportive care, monitoring for complications, and multidisciplinary interventions tailored to each patient’s needs.

Launched Drugs

Structure Generic Name CAS Registry Number Molecular Formula Molecular Weight
img-1217486-61-7-alpelisib-rec-inn-usan alpelisib (Rec INN; USAN) 1217486-61-7 C19 H22 F3 N5 O2 S 441.47

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Targets for Pik3Ca Related Overgrowth Spectrum

Targets in Clinical or Later Phases of Development

Target Name Gene Symbol
ATP binding cassette subfamily G member 2 (JR blood group) ABCG2
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CA
AKT serine/threonine kinase 2 AKT2
AKT serine/threonine kinase 1 AKT1
AKT serine/threonine kinase 3 AKT3
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CB
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CD
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3CG

The central therapeutic targets in PIK3CA-related overgrowth spectrum (PROS) are the PI3K/AKT pathway effectors, primarily the PI3K catalytic subunits (PIK3CA, PIK3CB, PIK3CD, PIK3CG) and the AKT serine/threonine kinases (AKT1, AKT2, AKT3). Activating mutations in PIK3CA drive constitutive activation of PI3K, resulting in excessive production of PIP3 and persistent downstream signaling through AKT and mTOR. These molecular alterations disrupt normal cell growth, proliferation, and survival, leading to the hallmark tissue overgrowth and vascular anomalies seen in PROS. Other PI3K isoforms and AKT kinases modulate the pathway’s activity and may influence disease severity or tissue-specific features, while their structural and regulatory domains provide multiple points for pharmacological intervention.

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Drug Discovery and Development Services

In Vitro Efficacy Testing ServicesIn Vivo Model DevelopmentPK/PD Study ServicesIn Vivo Toxicity Assessment ServicesBiomarker Analysis Services
In Vitro Efficacy Testing Services

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Our In Vitro Efficacy Testing Service accelerates drug discovery for PIK3CA Related Overgrowth Spectrum (PROS) by providing robust, high-throughput screening and characterization platforms. We utilize advanced biochemical and cell-based assays—including ATP, FRET, BRET, HTRF, chemiluminescence, and ELISA—to evaluate compound efficacy, mechanism of action, and pathway modulation. Key pharmacological parameters such as IC-50, Kd, and Ki are precisely measured across PI3K/AKT/mTOR pathway targets. Our integrated approach delivers comprehensive, actionable data, enabling effective candidate prioritization and optimization to support the development of targeted therapies for PROS and related overgrowth disorders.

Akt Serine/Threonine Kinase 1 Akt Serine/Threonine Kinase 2
Akt Serine/Threonine Kinase 3 Cytochrome P450 Family 3 Subfamily A Member 4
Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta
Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Delta Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma

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Why Choose Us

Choosing Protheragen for your PIK3CA related overgrowth spectrum (PROS) drug development needs means partnering with a company that brings specialized expertise and a deep understanding of this complex therapeutic area. At Protheragen, our dedicated teams consist of experienced scientists and industry professionals who are well-versed in the latest advances in PROS research and drug discovery. We utilize state-of-the-art technology platforms to ensure precision and efficiency at every stage of preclinical development. Protheragen has established a proven track record of reliability, successfully guiding numerous projects from concept to preclinical validation with a strong focus on client satisfaction. Our commitment to the highest quality standards and strict adherence to regulatory guidelines ensures that every project meets both scientific and compliance requirements. Above all, Protheragen is devoted to advancing therapeutics for PIK3CA related overgrowth spectrum, striving to bring innovative and effective treatment options to patients in need. With Protheragen, you gain a trusted partner dedicated to excellence, integrity, and meaningful progress in PROS drug development.

FAQs for Our Services

Q: What are the main preclinical research challenges specific to developing drugs for PIK3CA related overgrowth spectrum (PROS)?

A: One of the primary challenges in preclinical research for PROS is the heterogeneity of the disease, as it encompasses a spectrum of rare, mosaic disorders with varying clinical manifestations. Developing relevant in vitro and in vivo models that accurately recapitulate the genetic and phenotypic diversity of PROS is complex. Additionally, the mosaic nature of PIK3CA mutations complicates the assessment of drug efficacy and safety, necessitating highly sensitive and precise methods for detecting and quantifying mutant cell populations.

Q: What regulatory considerations should be taken into account when developing drugs for PIK3CA related overgrowth spectrum (PROS)?

A: Given the rarity and complexity of PROS, early and ongoing engagement with regulatory authorities is essential. Sponsors should consider applying for orphan drug designation to leverage regulatory incentives. It is also important to develop robust preclinical data packages that address both efficacy and safety, particularly because PROS patients may include pediatric populations. Regulatory agencies may require innovative approaches for preclinical model validation and biomarker development to support clinical translation.

Q: What are the key technical aspects to consider in preclinical research for PIK3CA related overgrowth spectrum (PROS)?

A: Technical considerations include the selection and validation of disease-relevant cellular and animal models, such as patient-derived cells or genetically engineered mouse models expressing PIK3CA mutations. Advanced molecular techniques, including digital PCR and next-generation sequencing, are necessary to detect low-frequency mosaic mutations. Furthermore, pharmacodynamic and pharmacokinetic assessments must be tailored to evaluate target engagement and tissue distribution in affected tissues.

Q: What are the typical timeline and cost considerations for preclinical drug development in PIK3CA related overgrowth spectrum (PROS)?

A: Preclinical development for PROS-targeted therapies typically spans 18-30 months, depending on the complexity of model development and regulatory requirements. Costs can vary widely, but the rarity and specialized nature of the disorder may increase expenses related to model generation, biomarker assay development, and specialized toxicology studies. Engaging a preclinical CRO with expertise in rare diseases and molecular genetics can help optimize timelines and manage costs.

Q: What are the critical success factors in preclinical drug development for PIK3CA related overgrowth spectrum (PROS)?

A: Key success factors include the development of robust, disease-relevant models that accurately reflect the mosaic and phenotypic nature of PROS, early identification and validation of pharmacodynamic biomarkers, and a clear regulatory strategy that leverages orphan drug pathways. Strong interdisciplinary collaboration—combining expertise in molecular genetics, pharmacology, and regulatory affairs—is essential to overcome technical and regulatory hurdles and to facilitate the successful translation of preclinical findings into clinical development.

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