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Accelerating Systemic Mastocytosis Drug Development

Systemic mastocytosis presents significant therapeutic challenges due to its complex pathophysiology and limited treatment options. Protheragen stands as a specialized partner in the development of novel therapeutics targeting systemic mastocytosis, offering a comprehensive suite of preclinical solutions that span target validation, lead optimization, and IND-enabling studies. Leveraging deep scientific expertise and advanced technological platforms, Protheragen integrates state-of-the-art in vitro and in vivo models with robust pharmacology and toxicology capabilities. Every project is executed with a stringent focus on regulatory compliance, ensuring a seamless transition from preclinical research to clinical development. Protheragen’s multidisciplinary team is dedicated to advancing innovative therapies with precision and speed, empowering clients to overcome the unique obstacles of systemic mastocytosis drug development. Through a commitment to scientific excellence and operational efficiency, Protheragen accelerates the path to therapeutic breakthroughs for patients in need.

What is Systemic MastocytosisTargets for Systemic MastocytosisDrug Discovery and Development ServicesWhy Choose Us

What is Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare clonal disorder characterized by the abnormal proliferation and accumulation of neoplastic mast cells in organs outside the skin, most commonly involving the bone marrow, liver, spleen, and gastrointestinal tract. The disease is most frequently driven by activating mutations in the KIT gene, particularly KIT D816V, which results in constitutive activation of the KIT receptor tyrosine kinase and promotes mast cell survival and proliferation. This leads to an excessive buildup of mast cells, which release mediators such as histamine and tryptase, contributing to the disease’s pathophysiology. Clinically, SM presents with a wide range of symptoms, from mild cutaneous manifestations like urticaria pigmentosa and flushing to severe complications such as anaphylaxis, gastrointestinal disturbances, osteoporosis, cytopenias, and organomegaly. Diagnosis relies on World Health Organization criteria, incorporating clinical assessment, serum tryptase measurement, bone marrow evaluation, immunohistochemistry, molecular testing for KIT mutations, and imaging to assess organ involvement. Treatment options depend on disease severity and subtype. Avapritinib and midostaurin, both KIT inhibitors, are approved for advanced SM, while imatinib is used in cases lacking the KIT D816V mutation. Cromolyn sodium may be prescribed for symptomatic relief by stabilizing mast cells and reducing mediator release.

Launched Drugs

Structure Generic Name CAS Registry Number Molecular Formula Molecular Weight
img-1703793-34-3-avapritinib-rec-inn-usan avapritinib (Rec INN; USAN) 1703793-34-3 C26 H27 F N10 498.558
img-120685-11-2-midostaurin-prop-inn-usan midostaurin (Prop INN; USAN) 120685-11-2 C35 H30 N4 O4 570.637
img-152459-95-5-free-base220127-57-1-imatinib-mesylate-rec-innm-usan imatinib mesylate (Rec INNM; USAN) 152459-95-5 (free base); 220127-57-1 C29 H31 N7 O . C H4 O3 S 589.708
img-15826-37-6-cromoglycate-sodiumcromolyn-sodium-usandisodium-cr cromoglycate sodium; cromolyn sodium (USAN); disodium cromoglycate; sodium cromoglycate (Prop INNM; BANM) 15826-37-6 C23 H14 O11 . 2 Na 512.33

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Targets for Systemic Mastocytosis

Targets in Clinical or Later Phases of Development

Target Name Gene Symbol
ABL proto-oncogene 1, non-receptor tyrosine kinase ABL1
ATP binding cassette subfamily B member 1 ABCB1
ATP binding cassette subfamily G member 2 (JR blood group) ABCG2
BCR activator of RhoGEF and GTPase BCR
G protein-coupled receptor 35 GPR35
fms related receptor tyrosine kinase 3 FLT3
colony stimulating factor 1 receptor CSF1R
KIT proto-oncogene, receptor tyrosine kinase KIT
phosphodiesterase 6D PDE6D
platelet derived growth factor receptor alpha PDGFRA

Systemic Mastocytosis (SM) is primarily driven by activating mutations in the KIT receptor tyrosine kinase, particularly KIT D816V, which leads to constitutive kinase activation and uncontrolled mast cell proliferation and survival. KIT is the central and most clinically validated target in SM, with downstream signaling through pathways such as MAPK, PI3K/AKT, and STAT. Additional receptor tyrosine kinases—including PDGFRA, PDGFRB, FGFR3, and FLT3—may act as co-drivers or modulators, especially in cases with overlapping myeloid neoplasms or resistance to KIT-targeted therapy. Non-receptor kinases like LYN and the serine/threonine kinase MTOR further contribute to aberrant signaling and mast cell persistence. Beyond kinases, anti-apoptotic regulators such as BCL2 and BCL2L1 are frequently upregulated in neoplastic mast cells, conferring resistance to cell death and supporting disease progression. Therapeutically, targeting KIT has yielded significant clinical advances; inhibitors such as midostaurin and avapritinib are approved for SM patients with KIT mutations, demonstrating reductions in mast cell burden and symptom relief. For patients lacking KIT mutations or with resistance, alternative kinase inhibitors (e.g., imatinib for PDGFRA mutations) and emerging agents against FLT3, FGFR3, or MTOR are under investigation. Targeting anti-apoptotic proteins like BCL2 (with agents such as venetoclax) represents a promising strategy to overcome resistance and induce mast cell apoptosis. Ongoing research aims to refine these targeted approaches, optimize combination regimens, and personalize therapy based on the molecular profile of each patient.

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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 Systemic Mastocytosis drug discovery by offering robust, sensitive platforms for screening candidate therapies. We utilize advanced cell-based and biochemical assays—including ATP, FRET, BRET, HTRF, chemiluminescent, and Rhodamine 123 accumulation—to evaluate compound potency, mechanism of action, and cellular responses. Key pharmacological parameters such as IC-50, Ki, and MIC are measured across critical targets like KIT, BTK, FLT3, and mTOR. This comprehensive approach enables high-throughput, quantitative analysis, supporting lead optimization, patient stratification, and informed therapeutic development for this rare hematologic disorder.

Abl Proto-Oncogene 1, Non-Receptor Tyrosine Kinase Atp Binding Cassette Subfamily B Member 1
Bruton Tyrosine Kinase Fms Related Receptor Tyrosine Kinase 3
Kit Proto-Oncogene, Receptor Tyrosine Kinase Lyn Proto-Oncogene, Src Family Tyrosine Kinase
Mechanistic Target Of Rapamycin Kinase Platelet Derived Growth Factor Receptor Alpha

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Why Choose Us

Choosing Protheragen means partnering with a team that is deeply committed to advancing therapeutics for Systemic mastocytosis. At Protheragen, we bring specialized expertise in Systemic mastocytosis research and drug development, ensuring that every project benefits from our in-depth understanding of the disease and its unique challenges. Our professional teams are supported by advanced technology platforms, enabling us to deliver innovative and effective solutions tailored to the needs of this complex field. Protheragen has established a strong track record in providing reliable preclinical drug development services, consistently meeting the expectations of our clients and partners. We adhere to the highest quality standards and maintain strict regulatory compliance throughout every stage of the development process, ensuring the safety and efficacy of our candidate therapeutics. Above all, Protheragen is dedicated to making a meaningful impact in the lives of patients with Systemic mastocytosis by driving the development of new and better treatment options. Our unwavering commitment and proven capabilities make us the trusted choice for your Systemic mastocytosis drug development needs.

FAQs for Our Services

Q: What are the main preclinical research challenges specific to developing drugs for Systemic mastocytosis?

A: Systemic mastocytosis (SM) is a rare and heterogeneous disease, making it challenging to establish robust preclinical models that accurately recapitulate the human condition. The scarcity of relevant cell lines and animal models, particularly those harboring the common KIT D816V mutation, can hinder efficacy and safety assessments. Our company addresses these challenges by leveraging advanced in vitro systems, genetically engineered mouse models, and patient-derived xenografts to provide comprehensive preclinical data tailored to SM.

Q: What regulatory considerations are important during preclinical development for Systemic mastocytosis therapies?

A: Given the orphan status of SM, regulatory authorities such as the FDA and EMA may offer expedited pathways and incentives, but they also require rigorous demonstration of safety and efficacy. It is crucial to design preclinical studies that meet regulatory expectations for rare diseases, including the selection of appropriate endpoints and biomarkers. Our regulatory experts guide clients through the preparation of IND-enabling studies, orphan drug designation applications, and interactions with regulatory agencies to ensure a smooth transition to clinical development.

Q: What are the key technical aspects to consider in preclinical research for Systemic mastocytosis?

A: Technical considerations include the selection of relevant in vitro assays (e.g., proliferation, apoptosis, and signaling pathway analyses in KIT-mutant mast cells), development of sensitive pharmacodynamic and pharmacokinetic assays, and the establishment of robust animal models. Our team utilizes state-of-the-art molecular biology, flow cytometry, and imaging techniques to assess drug efficacy and mechanism of action, ensuring that all technical aspects align with the unique biology of SM.

Q: What are the typical timeline and cost considerations for preclinical development of Systemic mastocytosis drug candidates?

A: Preclinical development for SM typically spans 12–24 months, depending on the complexity of the compound and the required studies. Costs can range from $1 million to $5 million, influenced by the need for specialized models and assays. Our company offers flexible, milestone-driven project plans and transparent budgeting to help clients manage timelines and costs effectively, while ensuring high-quality, regulatory-compliant results.

Q: What are the critical success factors in preclinical drug development for Systemic mastocytosis?

A: Success in SM drug development relies on early identification of compounds with high potency and selectivity for disease-driving mutations, robust preclinical efficacy and safety data, and the ability to translate preclinical findings to clinical settings. Our integrated approach—combining deep disease expertise, advanced model systems, regulatory guidance, and project management—maximizes the likelihood of preclinical success and smooth progression to clinical trials.

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