| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Itacnosertib (hydrocholide) targets three distinct kinases: JAK2 (Janus kinase 2), ACVR1 (activin A receptor type 1, also known as ALK2), and ALK5 (activin receptor-like kinase 5, also known as TGF-β receptor type I). JAK2 is a non-receptor tyrosine kinase that is involved in cytokine signaling and hematopoiesis, and is a well-established target for myeloproliferative neoplasms. ACVR1 (ALK2) is a bone morphogenetic protein (BMP) receptor that is involved in bone development and is mutated in fibrodysplasia ossificans progressiva. ALK5 is the type I receptor for TGF-β, a key regulator of fibrosis, inflammation, and cancer. By inhibiting these three kinases, Itacnosertib modulates multiple signaling pathways that are important in cancer and fibrotic diseases.
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| ln Vitro |
In vitro, Itacnosertib (hydrocholide) acts as an inhibitor of JAK2, ACVR1 (ALK2), and ALK5. The compound's multi-targeted kinase inhibition profile makes it a valuable tool for studying the roles of these kinases in various cellular processes. Specific quantitative data such as IC50 values for each kinase have not been extensively reported in the available literature. The compound's activity can be assessed in kinase assays using recombinant enzymes and appropriate substrates. The compound is used in research on signaling pathways involved in cancer and fibrosis. However, specific cell-based and in vivo data beyond the kinase inhibition profile have not been extensively reported.
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| ln Vivo |
In vivo activity data for Itacnosertib (hydrocholide) are not available in the current scientific literature. As a multi-targeted kinase inhibitor targeting JAK2, ACVR1, and ALK5, the compound would be expected to have effects on pathways involved in cancer and fibrosis. However, specific animal model studies, dosing regimens, and quantitative outcomes have not been reported. The compound's ability to inhibit multiple kinases suggests that it may have broad therapeutic potential, but further in vivo studies would be required to characterize its efficacy, safety, and pharmacokinetic properties in animal models of cancer and fibrotic diseases.
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| Enzyme Assay |
In vitro enzyme assay protocols for Itacnosertib (hydrocholide) would typically involve measuring its inhibition of JAK2, ACVR1 (ALK2), and ALK5 kinase activities. A standard protocol would involve incubating recombinant kinase enzymes with varying concentrations of Itacnosertib (typically 0.1 nM to 10 μM), ATP, and appropriate peptide substrates in kinase assay buffer at 30°C for a defined period. The extent of substrate phosphorylation is measured using methods such as 33P-ATP incorporation, TR-FRET, or luminescent kinase assays (e.g., ADP-Glo). IC50 values are determined from concentration-response curves for each kinase target. Selectivity profiling can be performed by testing the compound against a panel of kinases to assess its specificity.
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| Cell Assay |
In vitro cell-based assay protocols for Itacnosertib (hydrocholide) would typically involve assessing its effects on signaling pathways regulated by JAK2, ACVR1, and ALK5 in cultured cells. A standard protocol would involve treating cancer cells or cells relevant to fibrotic diseases with varying concentrations of Itacnosertib (typically 0.1 nM to 10 μM) for 24-72 hours. Signaling pathway modulation is assessed by Western blot analysis of phosphorylated STAT (for JAK2), SMAD1/5 (for ACVR1), and SMAD2/3 (for ALK5). Cell proliferation and viability are assessed using MTT or CellTiter-Glo assays. Apoptosis can be assessed by Annexin V staining or caspase activity assays. Appropriate controls include vehicle-treated cells and cells treated with selective inhibitors for each kinase.
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| Animal Protocol |
In vivo animal experimental protocols for Itacnosertib (hydrocholide) have not been reported in the available literature. Based on its multi-targeted kinase inhibition profile, potential studies might involve using mouse models of cancer or fibrosis. A hypothetical protocol for cancer studies would involve implanting cancer cells in immunodeficient mice and administering Itacnosertib via oral gavage or intraperitoneal injection at doses determined from preliminary pharmacokinetic and tolerability studies. For fibrosis studies, the compound could be administered in models of pulmonary fibrosis, liver fibrosis, or other fibrotic diseases. Endpoints would include tumor growth inhibition, assessment of signaling pathway modulation in tissues, and evaluation of fibrosis markers.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Itacnosertib (hydrocholide) have not been characterized in published studies. The compound has a molecular weight of 505.01 and a molecular formula of C26H29ClN8O. It is soluble in DMSO at 5.56 mg/mL (11.01 mM) with ultrasonic and warming to 60°C. The compound should be stored at 4°C, sealed, and protected from moisture. Specific PK parameters such as half-life, Cmax, AUC, bioavailability, volume of distribution, and clearance have not been reported. The compound's metabolism, protein binding, and routes of elimination remain to be characterized. Further pharmacokinetic studies would be required to understand its absorption, distribution, metabolism, and excretion profile.
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| References | |
| Additional Infomation |
Itacnosertib (hydrocholide) (TP-0184 (hydrocholide)) is a research-grade compound that functions as a multi-targeted inhibitor of JAK2, ACVR1 (ALK2), and ALK5. It has a molecular weight of 505.01. The compound is used in research on signaling pathways involved in cancer and fibrosis. It has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves inhibition of JAK2, ACVR1, and ALK5 kinases, modulating cytokine signaling, BMP signaling, and TGF-β signaling pathways. The compound is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
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| CAS # |
2409543-84-4
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| Appearance |
Off-white to light brown solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~5.56 mg/mL (~11.01 mM; with sonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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