| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
PKC-theta inhibitor 1 selectively targets protein kinase C theta (PKCθ) with a Ki of 6 nM. PKCθ is a calcium-independent, diacylglycerol-activated serine/threonine kinase that is predominantly expressed in T cells and skeletal muscle. In T cells, PKCθ is recruited to the immunological synapse upon T-cell receptor (TCR) engagement and is essential for the activation of transcription factors NF-kappaB, AP-1, and NFAT, which drive IL-2 production and T-cell proliferation. The compound shows excellent selectivity for PKCθ over other PKC isoforms including PKCalpha (Ki = 1020 microM) and PKCdelta (Ki = 392 microM).
|
|---|---|
| ln Vitro |
In vitro, PKC-theta inhibitor 1 exhibits potent inhibition of PKCθ with a Ki of 6 nM. The compound shows excellent selectivity for PKCθ over other PKC isoforms: PKCalpha (Ki = 1020 microM) and PKCdelta (Ki = 392 microM). In cellular assays, the compound inhibits IL-2 production with an IC₅0 of 0.19 microM. This inhibition of IL-2 production reflects the compound's ability to block PKCθ-mediated T-cell activation and NF-kappaB signaling. The high selectivity of PKC-theta inhibitor 1 for PKCθ over other PKC isoforms reduces the potential for off-target effects associated with pan-PKC inhibition.
|
| ln Vivo |
In vivo, PKC-theta inhibitor 1 reduces disease symptoms in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE). In this model, the compound demonstrates a reduction of clinical symptoms, indicating its potential as a therapeutic for autoimmune diseases. The compound also inhibits IL-2 production in vivo with an IC₅0 of 0.19 microM. The in vivo efficacy of PKC-theta inhibitor 1 supports the concept that PKCθ inhibition may provide a targeted approach to immunosuppression without the broad toxicity associated with global T-cell depletion or non-selective kinase inhibitors.
|
| Enzyme Assay |
In vitro enzyme assays for PKC-theta inhibitor 1 involve measuring PKCθ kinase activity using recombinant human PKCθ enzyme and a peptide substrate. The assay is performed in kinase buffer containing ATP, Mg2+, and phosphatidylserine/diacylglycerol as activators. Serial dilutions of the compound (0.001-100 microM) are incubated with the enzyme and substrate at 30degC for 30-60 minutes. Kinase activity is quantified by measuring phosphorylation of the peptide substrate using a fluorescence-based or radioactivity-based detection system (e.g., [33P]-ATP incorporation or ADP-Glo assay). IC₅0 and Ki values are determined from dose-response curves. Selectivity is assessed by screening against a panel of protein kinases including other PKC isoforms (alpha, beta, gamma, delta, ε, η, zeta) and unrelated kinases.
|
| Cell Assay |
Cellular assays for PKC-theta inhibitor 1 are performed using T-cell lines or primary human T cells. Human peripheral blood mononuclear cells (PBMCs) are isolated from whole blood by density gradient centrifugation. T cells are purified using magnetic bead separation. Cells are cultured in RPMI-1640 medium supplemented with 10% FBS and stimulated with anti-CD3/anti-CD28 antibodies or phytohemagglutinin (PHA) in the presence of serial dilutions of the compound (0.001-10 microM) for 24-48 hours. IL-2 production in the supernatant is quantified by ELISA. T-cell proliferation is measured by [3H]-thymidine incorporation or CFSE dilution. NF-kappaB activation is assessed by Western blotting for IkappaBalpha degradation or p65 phosphorylation. IC₅0 values for inhibition of IL-2 production are calculated.
|
| Animal Protocol |
In vivo animal studies for PKC-theta inhibitor 1 are conducted in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Female C57BL/6 mice are immunized with myelin oligodendrocyte glycoprotein (MOG3₅₋₅₅) peptide emulsified in complete Freund's adjuvant supplemented with Mycobacterium tuberculosis. Pertussis toxin is administered intraperitoneally on days 0 and 2. Animals are randomized into treatment groups and administered PKC-theta inhibitor 1 orally or intraperitoneally at doses of 10-50 mg/kg daily from day 7 post-immunization. Clinical scores are assessed daily using a 0-5 scale. At the end of the study, spinal cords and brains are collected for histopathological analysis (H&E and Luxol fast blue staining) and immunohistochemistry for inflammatory markers.
|
| ADME/Pharmacokinetics |
PKC-theta inhibitor 1 (CAS#: 1160501-81-4) has molecular formula C1₇H1₅F3N4O and molecular weight 348.32. The compound is a solid and is soluble in DMSO. It is a potent PKCθ inhibitor with a Ki of 6 nM, excellent selectivity over PKCalpha (Ki = 1020 microM) and PKCdelta (Ki = 392 microM), and in vivo efficacy in a mouse model of multiple sclerosis. The compound is a research chemical for laboratory use only. It is not for human therapeutic applications. The compound should be stored at -20degC, protected from light and moisture.
|
| Toxicity/Toxicokinetics |
Toxicological information for PKC-theta inhibitor 1 is limited as the compound is a research chemical. Based on its mechanism of PKCθ inhibition in T cells, potential adverse effects may include immunosuppression, increased susceptibility to infections, and impaired immune responses. The compound should be handled with standard laboratory precautions including the use of personal protective equipment and working in a well-ventilated area. Avoid inhalation, ingestion, and skin contact. The compound should be stored at -20degC and disposed of according to institutional guidelines for chemical waste.
|
| References | |
| Additional Infomation |
PKC-theta inhibitor 1 (CAS#: 1160501-81-4) is a potent and selective PKCθ inhibitor with a Ki of 6 nM. PKCθ is a key signaling molecule in T-cell activation and is required for IL-2 production, T-cell proliferation, and the pathogenesis of autoimmune diseases. The compound exhibits excellent selectivity for PKCθ over other PKC isoforms including PKCalpha and PKCdelta. PKC-theta inhibitor 1 has been shown to reduce disease symptoms in a mouse model of multiple sclerosis (EAE), demonstrating its potential as a therapeutic for autoimmune disorders. The compound is supplied for research use only and is not approved for clinical use. As of the current date, PKC-theta inhibitor 1 remains a preclinical research compound.
|
| Molecular Formula |
C17H15F3N4O
|
|---|---|
| Molecular Weight |
348.32
|
| Exact Mass |
348.119
|
| CAS # |
1160501-81-4
|
| PubChem CID |
57969746
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.1
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
25
|
| Complexity |
485
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O1CC(C2=CC=CC(C3C=CN=C4NN=C(C(F)(F)F)C4=3)=C2)(CN)C1
|
| InChi Key |
WQSBBBAQXNAUEM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H15F3N4O/c18-17(19,20)14-13-12(4-5-22-15(13)24-23-14)10-2-1-3-11(6-10)16(7-21)8-25-9-16/h1-6H,7-9,21H2,(H,22,23,24)
|
| Chemical Name |
[3-[3-[3-(trifluoromethyl)-2H-pyrazolo[3,4-b]pyridin-4-yl]phenyl]oxetan-3-yl]methanamine
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8709 mL | 14.3546 mL | 28.7092 mL | |
| 5 mM | 0.5742 mL | 2.8709 mL | 5.7418 mL | |
| 10 mM | 0.2871 mL | 1.4355 mL | 2.8709 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
