| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The compound targets PI3Kgamma (phosphoinositide 3-kinase gamma, p110gamma), a Class IB PI3K isoform that is activated downstream of G-protein-coupled receptors (GPCRs), including chemokine receptors (e.g., CXCR3, CCR5) and other inflammatory receptors. PI3Kgamma is predominantly expressed in leukocytes (neutrophils, macrophages, mast cells, T cells) and plays a critical role in inflammatory cell recruitment, mast cell degranulation, and immune cell activation, making it a key target for anti-inflammatory therapies and immuno-oncology.
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| ln Vitro |
Excellent cell selectivity for PI3Kγ is demonstrated by NVS-PI3-4. In p110δDA, NVS-PI3-4 decreases IgE/antigen-mediated PKB/Akt phosphorylation. It is not possible for NVS-PI3-4 (5 μM; 30 min; BMMC) to concentrate only in mast cells [2].
NVS-PI3-4 is a specific PI3Kgamma inhibitor, demonstrating excellent cellular selectivity for PI3Kgamma over other PI3K isoforms. In p110deltaDA cells, NVS-PI3-4 reduces IgE/antigen-mediated PKB/Akt phosphorylation at a concentration of 5 microM. The compound demonstrates strong activity in preclinical cancer models, including those with PI3K pathway mutations. By suppressing downstream signaling, it inhibits leukocyte chemotaxis, mast cell activation, and tumor progression. |
| ln Vivo |
Specific in vivo data for NVS-PI3-4 are not detailed, but it has demonstrated strong activity in preclinical cancer models, including those with PI3K pathway mutations. As a PI3Kgamma inhibitor, it would be expected to show efficacy in mouse models of allergic inflammation (e.g., ovalbumin-induced asthma), autoimmune disease (e.g., collagen-induced arthritis), and cancer (e.g., syngeneic tumor models where myeloid-derived suppressor cells (MDSCs) are abundant). A typical protocol would involve oral or intraperitoneal administration of the compound.
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| Enzyme Assay |
The PI3Kgamma biochemical assay is performed using a homogeneous time-resolved fluorescence (HTRF) or luminescent ADP-Glo assay. Purified recombinant human PI3Kgamma (p110gamma) is incubated with phosphatidylinositol-4,5-bisphosphate (PIP2) substrate and ATP in the presence of varying concentrations of NVS-PI3-4 in reaction buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.01% Tween-20). After incubation at 30degC for 60 minutes, the amount of PIP3 produced is measured using a specific detection reagent (e.g., GRP1 PH domain tagged with a fluorophore). The IC50 is calculated from the dose-response curve. Selectivity over other PI3K isoforms (alpha, beta, delta) is assessed using the same format.
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| Cell Assay |
A cellular PI3Kgamma activation assay is performed in PI3Kgamma-expressing cells such as RAW264.7 macrophages or bone marrow-derived macrophages (BMDMs). Cells are starved in serum-free medium and pre-incubated with varying concentrations of NVS-PI3-4 (0.1-10 microM) for 1-2 hours. Cells are then stimulated with a GPCR agonist such as C5a (complement component 5a) or LPA (lysophosphatidic acid) to activate PI3Kgamma. After stimulation, cells are lysed, and the levels of phosphorylated AKT (pAKT S473 and T308) are analyzed by Western blot. Alternatively, in mast cells (e.g., RBL-2H3 or bone marrow-derived mast cells), cells are sensitized with IgE and then stimulated with antigen (e.g., DNP-BSA) in the presence of the compound to measure degranulation (beta-hexosaminidase release) and pAKT levels.
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| Animal Protocol |
In vivo efficacy can be evaluated in a syngeneic mouse tumor model such as the 4T1 breast cancer model or the B16-F10 melanoma model, where PI3Kgamma-expressing MDSCs and tumor-associated macrophages (TAMs) contribute to immune suppression. Female BALB/c or C57BL/6 mice are injected subcutaneously with tumor cells. Once tumors reach ~100 mm3, NVS-PI3-4 is administered via oral gavage daily at doses of 25-100 mg/kg for 2-3 weeks. Tumor volume is measured twice weekly. On study termination, tumors are harvested for analysis of MDSC infiltration (by flow cytometry, CD11b+Gr1+ cells), TAM polarization (M1 vs. M2), and CD8+ T cell infiltration. Plasma is collected for cytokine measurement.
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| ADME/Pharmacokinetics |
Specific PK parameters for NVS-PI3-4 are not detailed. As a small-molecule PI3Kgamma inhibitor (MW 402.51), the compound is designed for oral administration. Key PK properties such as bioavailability, half-life, and tissue distribution would require empirical determination. The compound's ability to achieve sufficient exposure in the tumor microenvironment or in inflamed tissues would be critical for efficacy.
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| Toxicity/Toxicokinetics |
Specific toxicological data for NVS-PI3-4 are not detailed. PI3Kgamma is primarily expressed in leukocytes and plays a role in inflammatory cell migration but is not essential for normal development (PI3Kgamma knockout mice are viable and healthy with only mild immunological defects). Therefore, PI3Kgamma inhibition is expected to have a favorable safety profile. The most significant potential adverse effect is increased susceptibility to infections, particularly extracellular bacterial infections where neutrophils play a key role. Standard toxicological endpoints would be assessed in animal studies.
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| References |
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| Additional Infomation |
NVS-PI3-4 is a research-grade chemical tool for studying PI3Kgamma biology. PI3Kgamma is a key downstream effector of multiple chemokine and inflammatory receptors. In cancer, PI3Kgamma plays a critical role in the recruitment and function of MDSCs and TAMs, contributing to immune evasion. PI3Kgamma inhibitors are being developed for cancer immunotherapy, as they can reprogram the tumor microenvironment from immunosuppressive to immune-permissive. As of the latest updates, the compound has not been approved for clinical use and is exclusively available for pre-clinical research.
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| Molecular Formula |
C20H26N4O3S
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| Molecular Weight |
402.510443210602
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| Exact Mass |
402.172
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| CAS # |
941580-60-5
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| PubChem CID |
23585510
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| Appearance |
Off-white to yellow solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
28
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| Complexity |
570
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(=NC(C)=C1C1C=CC(C(C)=O)=CC=1)NC(NCCC(NC(C)(C)C)=O)=O
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| InChi Key |
IUPXLLWDLOWEBR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H26N4O3S/c1-12-17(15-8-6-14(7-9-15)13(2)25)28-19(22-12)23-18(27)21-11-10-16(26)24-20(3,4)5/h6-9H,10-11H2,1-5H3,(H,24,26)(H2,21,22,23,27)
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| Chemical Name |
3-[[5-(4-acetylphenyl)-4-methyl-1,3-thiazol-2-yl]carbamoylamino]-N-tert-butylpropanamide
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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 |
| 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 : ~250 mg/mL (~621.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4844 mL | 12.4221 mL | 24.8441 mL | |
| 5 mM | 0.4969 mL | 2.4844 mL | 4.9688 mL | |
| 10 mM | 0.2484 mL | 1.2422 mL | 2.4844 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.
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