We provide robust and sensitive in vitro screening and characterization platforms for accelerating the discovery and screening of potential therapies for Immunodeficiency Disorders. Our service offers comprehensive functional and biochemical assays to evaluate immune cell function, signaling pathway integrity, and protein interactions that are critical in immunodeficiencies. Key targets include cytokines, immune cell receptors, and enzymes central to immune response modulation and pathogen defense. We assess defects in immune cell activation, signal transduction, and protein-protein interactions associated with the pathological processes underlying immunodeficiency disorders.
Our portfolio includes a diverse array of in vitro testing methods, such as enzymatic activity, binding affinity, and cell-based functional assays, to thoroughly characterize therapeutic candidates. These methods enable precise measurement of drug efficacy, target engagement, and mechanism of action, supporting both early discovery and lead optimization.
ATP assay: Measures cellular energy status and viability, providing insights into immune cell function and cytotoxicity.
Acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin substrate assay: Detects caspase activity linked to apoptosis, relevant for assessing immune cell survival.
Acetyl-Leu-Arg-Ser-Arg-7-amino-4-methylcoumarin substrate assay: Evaluates serine protease activity, important for monitoring immune response pathways.
Chemiluminescent assay: Offers sensitive detection of target proteins or enzymatic activity through light emission, supporting high-throughput screening.
Competitive binding assay (qPCR): Quantifies binding affinity and specificity of compounds to immune targets using competitive displacement and quantitative PCR readout.
ELISA assay: Enables quantification of cytokines, antibodies, or other immune mediators, providing critical information on immune modulation.
Luciferine/luciferase assay: Reports on gene expression, promoter activity, or cell viability via luminescence, aiding in pathway and functional studies.
Surface plasmon resonance assay: Provides real-time analysis of biomolecular interactions and binding kinetics, essential for characterizing drug-target engagement.
We measure key pharmacological parameters such as EC-50, IC-50, Kd, and Ki to quantify drug potency, efficacy, and binding affinity. These data are crucial for comparing candidate therapeutics and optimizing lead compounds for clinical development.
EC-50: The concentration of a compound that produces 50% of its maximal effect, indicating drug potency in functional assays.
IC-50: The concentration required to inhibit a biological or biochemical function by 50%, used to assess inhibitor strength.
Kd: The equilibrium dissociation constant, reflecting the affinity between a drug and its target; lower Kd values indicate higher affinity.
Ki: The inhibitor constant, representing the binding affinity of an inhibitor for its target enzyme or receptor, important for lead optimization.
The Aryl Hydrocarbon Receptor (AhR) plays a crucial role in immune regulation and is implicated in immunodeficiency disorders. AhR testing is vital for drug development, helping identify compounds that modulate immune responses. Our service utilizes luciferin/luciferase reporter assays to quantify AhR activity, providing precise IC-50 values to assess compound potency. This enables efficient screening and optimization of immunomodulatory drug candidates targeting AhR pathways.
| Pharmacological Activity | Material | Method | Parameter |
|---|---|---|---|
| Gene (Ahr) transcription (VAF-347-induced), inhibition | HepG2 human hepatoblastoma cells | Luciferine/luciferase assay | IC-50 |
| Gene (Ahr) transcription (VAF-347-induced), inhibition | HepG2 human hepatoblastoma cells transfected with luciferase | Luciferine/luciferase assay | IC-50 |
| Gene (Ahr) transcription, inhibition | HepG2 human hepatoblastoma cells | Luciferine/luciferase assay | IC-50 |
| Gene (xenobiotic response element-dependent) transcription (VAF347-induced), inhibition | HepG2 human hepatoblastoma cells | Luciferine/luciferase assay | IC-50 |
| Gene (xenobiotic response element-dependent) transcription, inhibition | HepG2 human hepatoblastoma cells | Luciferine/luciferase assay | IC-50 |
Our Caspase 3 testing service supports Immunodeficiency Disorders drug development by measuring Caspase 3 activity, a key mediator of apoptosis implicated in immune cell regulation. This assay is essential for evaluating drug effects on apoptotic pathways. Using Acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin as a fluorogenic substrate, we determine compound potency via IC₅₀ values, enabling precise assessment of therapeutic candidates targeting caspase-mediated immune modulation.
| Pharmacological Activity | Material | Method | Parameter |
|---|---|---|---|
| Caspase-3, inhibition | Human enzyme | IC-50 | |
| Caspase-3, inhibition | Acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin as substrate | IC-50 |
Cereblon, a substrate receptor of the CRL4 E3 ubiquitin ligase complex, modulates immune cell function and is implicated in immunodeficiency disorders. Cereblon testing is vital for identifying drug targets and patient stratification in drug development. Key methods include gene sequencing, protein expression analysis, and functional assays. Main parameters assessed are cereblon gene variants, protein levels, and ubiquitination activity, providing crucial insights for therapeutic strategies.
| Pharmacological Activity | Method | Parameter |
|---|---|---|
| Cereblon/Damage-specific DNA binding protein 1 interaction, inhibition | Fluorescent polarization assay | Ki |
Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4) regulates immune responses and its dysfunction is linked to immunodeficiency disorders. Testing CTLA-4 is crucial for developing targeted therapies. Our service utilizes the luciferin/luciferase assay to assess CTLA-4 activity and inhibition, providing precise IC-50 measurements. This enables accurate evaluation of drug efficacy in modulating CTLA-4, supporting drug development for immunodeficiency conditions.
| Pharmacological Activity | Material | Method | Parameter |
|---|---|---|---|
| Cytotoxic lymphocyte-associated antigen-4 (CTLA-4)/Lipopolysaccharide-responsive beige-like anchor protein (LRBA)-interaction, inhibition | HEK293 human embryonic kidney cells | Luciferine/luciferase assay | IC-50 |
Interleukin 1 Receptor Associated Kinase 4 (IRAK4) plays a pivotal role in immune signaling, and its dysfunction is linked to immunodeficiency disorders. IRAK4 testing is crucial for drug development, enabling assessment of compound efficacy and potency. Our service utilizes chemiluminescent and ATP assays to reliably quantify IRAK4 activity, measuring key parameters such as EC-50 and IC-50, which inform compound effectiveness and guide therapeutic optimization.
| Pharmacological Activity | Material | Method | Parameter |
|---|---|---|---|
| Serine/threonine protein kinase (IRAK-4) degradation, induction | OCI-Ly10 human diffuse large B-cell lymphoma cells | Chemiluminescent assay | EC-50 |
| Serine/threonine protein kinase (IRAK-4), inhibition | Recombinant human enzyme | ATP assay | IC-50 |
Malt1 Paracaspase is crucial for immune cell signaling, and its dysfunction is linked to immunodeficiency disorders. Testing Malt1 activity is vital for drug development targeting these conditions. Our service uses Acetyl-Leu-Arg-Ser-Arg-7-amino-4-methylcoumarin substrate in chemiluminescent assays, as well as surface plasmon resonance and ELISA methods. Key parameters measured include EC-50, IC-50, and Kd, enabling precise assessment of compound potency and binding affinity.
| Pharmacological Activity | Material | Method | Parameter |
|---|---|---|---|
| B-cell lymphoma 10 protein (BCL-10) cleavage, inhibition | OCI-Ly3 human diffuse large B-cell lymphoma cells | ELISA assay | IC-50 |
| Mucosa associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (E397A-mutated) affinity | B-Lymphocytes, human (immunosuppressed) | Surface plasmon resonance assay | Kd |
| Mucosa associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (W580S-mutated) affinity | B-Lymphocytes, human (immunosuppressed) | Surface plasmon resonance assay | Kd |
| Mucosa associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (W580S-mutated) stabilization, induction | B-Lymphocytes, human (immunosuppressed) | Chemiluminescent assay | EC-50 |
| Mucosa associated lymphoid tissue lymphoma translocation protein 1 (MALT1) affinity | B-Lymphocytes, human (immunosuppressed) | Surface plasmon resonance assay | Kd |
| Mucosa associated lymphoid tissue lymphoma translocation protein 1 (MALT1), inhibition | Recombinant human protein | Acetyl-Leu-Arg-Ser-Arg-7-amino-4-methylcoumarin as substrate | IC-50 |
Phosphatidylinositol-5-Phosphate 4-Kinase Type 2 Gamma (PI5P4K2C) plays a crucial role in immune cell signaling, and its dysregulation is linked to immunodeficiency disorders. Testing PI5P4K2C activity is vital for drug development targeting immune dysfunction. Our service utilizes chemiluminescent and competitive binding (qPCR) assays to measure enzyme activity and inhibitor potency, providing key parameters such as EC-50 and Ki to guide therapeutic candidate selection.
| Pharmacological Activity | Material | Method | Parameter |
|---|---|---|---|
| Phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP5K2C) affinity | Recombinant enzyme | Competitive binding assay (qPCR) | Ki |
| Phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP5K2C) degradation, induction | MOLT4 human acute T-lymphoblastoid leukemia cells | Chemiluminescent assay | EC-50 |
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