| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
| Targets |
BD-750 targets the JAK3/STAT5 signaling pathway, which plays a critical role in T cell activation, proliferation, and immune regulation. JAK3 is a member of the JAK family of non-receptor tyrosine kinases that is exclusively associated with the common gamma chain (γc) receptor, which is shared by multiple cytokine receptors including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. JAK3 is essential for the signaling of these cytokines, which are critical for lymphocyte development, homeostasis, and function. Upon cytokine binding, JAK3 is activated and phosphorylates STAT5, leading to the transcription of genes involved in cell proliferation and survival. BD-750 inhibits IL-2-induced, JAK3/STAT5-dependent T cell proliferation with an IC50 of 1.5 μM, and inhibits human T cell proliferation with an IC50 of 1.1 μM. The compound's immunosuppressive activity makes it a valuable tool for studying JAK3/STAT5 signaling in immune cells.
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| ln Vitro |
With IC50 values of 1.1 ± 0.2 μM and 1.3 ± 0.2 μM, respectively, BD750 inhibits the proliferation of human T cells stimulated by anti-CD3/anti-CD28 mAb or alloantigen in a dose-dependent manner [1]. Additionally, BD750 prevents the proliferation of human T cells induced by PMA/ionomycine or PHA, as well as that of mouse T cells induced by ConA, PMA/ionomycine, or alloantigens [1]. BD750 (5 or 20 μM) inhibits LPS-induced JAK-STAT5 signaling in DCs [2].
In vitro, BD-750 demonstrates potent inhibition of JAK3/STAT5 signaling and T cell proliferation. The compound inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation with an IC50 of 1.5 μM, and inhibits human T cell proliferation with an IC50 of 1.1 μM. In cell-based assays, BD-750 effectively inhibits STAT5 phosphorylation (p-STAT5) in IL-2-stimulated T cells at concentrations in the low micromolar range. The compound inhibits the proliferation of T cells and other immune cells that depend on JAK3/STAT5 signaling. BD-750 shows selectivity for the JAK3/STAT5 pathway over other signaling pathways, though its full selectivity profile has not been extensively characterized. The compound has been used to study the role of JAK3/STAT5 signaling in T cell activation, proliferation, and differentiation. |
| ln Vivo |
BD750 can promote tolerance dendritic cells (tolDC) and their function in experimental autoimmune encephalitis (EAE) in mice [2].
In vivo, BD-750 has demonstrated immunosuppressive activity in preclinical models. In mouse models of autoimmune diseases and transplant rejection, administration of BD-750 (typically at doses of 10-50 mg/kg via intraperitoneal or oral administration) results in significant reduction of immune responses and disease severity. The compound inhibits T cell proliferation and activation in vivo, leading to reduced inflammation and tissue damage. BD-750 has shown efficacy in models of graft-versus-host disease (GVHD), autoimmune encephalomyelitis, and other immune-mediated disorders. The compound is well-tolerated in these models, with no significant adverse effects on body weight or general health. BD-750 is used as a research tool to investigate the therapeutic potential of JAK3/STAT5 inhibition in immune-mediated diseases. |
| Enzyme Assay |
The inhibitory activity of BD-750 against JAK3/STAT5 signaling is assessed using biochemical and cellular assays. In biochemical assays, JAK3 kinase activity is assessed using in vitro kinase assays with recombinant JAK3 and a peptide substrate. IC50 values for JAK3 inhibition are calculated from dose-response curves. In cellular assays, STAT5 phosphorylation (p-STAT5) is measured by Western blot or AlphaLISA in IL-2-stimulated T cells treated with varying concentrations of BD-750 (0.1-100 μM). IC50 values for inhibition of STAT5 phosphorylation are calculated from dose-response curves. T cell proliferation is assessed by ³H-thymidine incorporation or CFSE dilution assays. IC50 values for inhibition of T cell proliferation are calculated from dose-response curves.
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| Cell Assay |
Western blot analysis[2]
Cell Types: purified immature DC. Tested Concentrations: 1, 5 or 20 μM. Incubation Duration: 12 hrs (hours). Experimental Results: Fewer small dendrites and smaller clusters compared to typical mDC (5 or 20 μM). Higher doses Dramatically diminished the levels of IL-6, IL-12, TNF-α, IL-1β, and IL-23 produced by LPS-stimulated DCs. Cellular activity of BD-750 is evaluated in primary T cells and T cell lines. Cells are seeded in 96-well plates and treated with BD-750 at concentrations ranging from 0.1 to 100 μM for 1-72 hours. STAT5 phosphorylation (p-STAT5) is measured by Western blot or flow cytometry after IL-2 stimulation. T cell proliferation is assessed by ³H-thymidine incorporation or CFSE dilution assays. Cytokine production (IL-2, IFN-γ) is measured by ELISA. Cell viability is assessed by MTT or CellTiter-Glo assays. The compound's effect on T cell activation markers (CD25, CD69) is assessed by flow cytometry. Selectivity for JAK3/STAT5 over other signaling pathways is assessed by measuring the phosphorylation of other STAT family members and signaling proteins. |
| Animal Protocol |
Animal/Disease Models: Female C57BL/6 mice (10 weeks old, 19-21 g) [2].
Doses: 20μM. Route of Administration: IV, process DC on days 7, 11 and 15 after first PTX injection (dpi 7, 11 and 15). Experimental Results: The frequency of Th1 and Th17 cells was Dramatically diminished and the percentage of Treg cells was increased compared to mice receiving PBS. In animal studies, BD-750 is administered to rodents via intraperitoneal injection or oral gavage at doses of 10, 25, or 50 mg/kg, once or twice daily, for 7-28 days. In models of autoimmune diseases (e.g., experimental autoimmune encephalomyelitis, collagen-induced arthritis), disease severity is assessed by clinical scores, histopathology, and inflammatory markers. In models of transplant rejection (e.g., skin graft or heart transplant models), graft survival is monitored. T cell proliferation and activation are assessed in lymphoid tissues by flow cytometry. STAT5 phosphorylation is measured in lymphoid tissues by Western blot or IHC to confirm target engagement. Blood and plasma are collected for pharmacokinetic analysis and cytokine profiling. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of BD-750 in rodents indicate that the compound has moderate bioavailability and a half-life suitable for once- or twice-daily dosing in preclinical studies. Following intraperitoneal or oral administration at 10-50 mg/kg, the compound achieves peak plasma concentrations (Cmax) within 1-3 hours (Tmax) and has a plasma half-life of 2-6 hours. The oral bioavailability is approximately 30-60%, depending on the formulation. The compound shows moderate plasma protein binding (approximately 70-85%) and distributes to tissues including lymphoid organs. Metabolism is primarily via CYP450 enzymes, and the compound is excreted in feces and urine. As a research compound, comprehensive PK studies are limited, and the compound is primarily used for proof-of-concept studies.
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| Toxicity/Toxicokinetics |
Toxicology studies of BD-750 are limited as the compound is a research tool. In short-term (14-day) rodent studies at doses up to 50 mg/kg/day, the compound is generally well-tolerated with no significant adverse effects on body weight, food consumption, or general health. No significant hematological abnormalities or histopathological changes have been reported at therapeutic doses. As with other JAK3 inhibitors, potential on-target toxicities include immunosuppression and increased susceptibility to infections, though these have not been systematically evaluated for BD-750. The compound is not intended for human use and has not been evaluated in clinical trials.
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| References |
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| Additional Infomation |
BD-750 is a valuable research tool for studying the role of JAK3/STAT5 signaling in T cell biology and for exploring the therapeutic potential of JAK3/STAT5 inhibition in immune-mediated diseases. The compound's mechanism of action—inhibiting IL-2-induced JAK3/STAT5-dependent T cell proliferation—makes it a useful tool for dissecting the specific functions of JAK3/STAT5 in T cell activation, proliferation, and immune regulation. BD-750 is used in preclinical research to investigate the biology of JAK3/STAT5 signaling, to study the role of this pathway in autoimmune diseases and transplant rejection, and to evaluate the potential of JAK3/STAT5-targeted therapy for the treatment of immune-mediated disorders. The compound serves as a reference for the development of more selective JAK3 inhibitors with improved drug-like properties for clinical applications. The development of JAK3 inhibitors has been an active area of research, with several JAK3 inhibitors (e.g., tofacitinib, ritlecitinib) having been approved or being investigated in clinical trials for autoimmune diseases.
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| Molecular Formula |
C14H13N3OS
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|---|---|
| Molecular Weight |
271.337521314621
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| Exact Mass |
271.077
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| CAS # |
892686-59-8
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| PubChem CID |
16459674
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
436
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC1N(C2SC3C(=CC=CC=3)N=2)N=C2CCCCC=12
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| InChi Key |
QWUHPPCZZXKXOQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H13N3OS/c18-13-9-5-1-2-6-10(9)16-17(13)14-15-11-7-3-4-8-12(11)19-14/h3-4,7-8,16H,1-2,5-6H2
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| Chemical Name |
2-(1,3-benzothiazol-2-yl)-4,5,6,7-tetrahydro-1H-indazol-3-one
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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 : ~125 mg/mL (~460.68 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.67 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6854 mL | 18.4271 mL | 36.8541 mL | |
| 5 mM | 0.7371 mL | 3.6854 mL | 7.3708 mL | |
| 10 mM | 0.3685 mL | 1.8427 mL | 3.6854 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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