| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Other Sizes |
| Targets |
Bruton's tyrosine kinase (BTK), with IC50 = 1.95 nM. BMX (IC50 = 0.64 nM, 0.3-fold selectivity), TEC (2.3-fold), TXK (2.4-fold). Poseltinib covalently binds to the active site Cys481 residue of BTK.
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| ln Vitro |
In B cells, poseltinib (0.1–100 nM, 30 min) suppresses FcR and BCR signaling [1]. At dosages activated in activated Ramos B cells, poseltinib (1-1000 nM, 1 h) suppresses human monocyte production of interleukin (IL)-6, tumor factor (TNF)-alpha, and primary human B cells. The inhibition of human monocytogenes by IL-1β results in the inhibition of Btk's phosphorylation and that of its downstream components, including PLCγ2. In PBMCs, poseltinib (30 μM, 15 min) suppresses the phosphorylation of BTK, AKT, and PLCγ2 [3].
Poseltinib effectively inhibits signaling mediated by B-cell receptors (BCR), Fc receptors (FcR), and Toll-like receptors (TLR). It exhibits potent BTK inhibition with an IC50 of 1.95 nM. The compound shows 0.3-, 2.3-, and 2.4-fold higher selectivity for BTK over BMX, TEC, and TXK, respectively. This distinct selectivity profile enables clean dissection of TEC-family kinase signaling in BCR, FcR, and TLR pathways. Poseltinib has anti-inflammatory activity and can be used in research of rheumatoid arthritis. |
| ln Vivo |
Poseltinib (3–30 mg/kg, lateral, once daily, from 18–40 weeks) inhibits BTK, which lowers B cell hyperactivity and attenuates lupus erythematosus (SLE) and lupus nephritis (LN) in mice. Poseltinib (1–30 mg/kg, lateral, once daily during the day) was created to alleviate experimental arthritis in mice [2].
Poseltinib demonstrates in vivo efficacy in autoimmune disease models. In the collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis, Poseltinib shows an ED90 of 6.0 mg/kg/day. The compound has been extensively characterized in autoimmune and inflammatory disease models. Its oral bioavailability and irreversible BTK inhibition enable sustained target engagement in vivo. Studies validate its potential for treating autoimmune conditions through modulation of B-cell and Fc receptor-mediated inflammatory pathways. |
| Enzyme Assay |
BTK kinase activity assays are performed using recombinant human BTK enzyme and a peptide substrate in a kinase reaction buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.01% BSA, 0.1 mM Na3VO4). ATP is added at Km concentration, and the reaction is incubated at 30°C for 30-60 minutes. Phosphorylated substrate is quantified using a homogeneous time-resolved fluorescence (HTRF) or luminescence-based detection system. Test compounds are serially diluted in DMSO and added to the reaction mixture. IC50 values are determined by fitting dose-response curves using non-linear regression analysis. Each concentration is tested in duplicate.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: B Cell Tested Concentrations: Nucleated cells form osteoclasts[2]. 0.1-100 nM Incubation Duration: 30 minutes Experimental Results: Blocks the autophosphorylation of BTK and the phosphorylation of PLCγ2, with an IC50 value less than 10 nM. Reduces TNF-α and IL-6 production in a dose-dependent manner. Cellular BTK inhibition is evaluated in B-cell lines (e.g., Ramos, Raji) or primary B cells isolated from human or mouse blood. Cells are cultured in RPMI-1640 with 10% FBS and treated with Poseltinib at various concentrations (0.01-10 μM) for 1-4 hours. BTK autophosphorylation at Tyr223 is measured by Western blotting or ELISA using phospho-specific antibodies. BCR-induced calcium flux is assessed using Fluo-4 AM dye and flow cytometry. Phosphorylation of downstream signaling proteins (PLCγ2, ERK, AKT) is measured by Western blotting. Cell viability is assessed using MTT or CellTiter-Glo assays. Each experiment includes vehicle controls and positive controls. |
| Animal Protocol |
Animal/Disease Models: MRL/lpr mouse and NZB/W F1 mouse model [1]. ]
Doses: 3-30 mg/kg Route of Administration: Oral Experimental Results: Reduce spleen weight and prevent progression of skin lesions. Improves kidney damage and inflammation and improves survival. In vivo efficacy is evaluated in the collagen-induced arthritis (CIA) mouse model. DBA/1 mice are immunized with bovine type II collagen in Freund's complete adjuvant. Poseltinib is administered orally at doses ranging from 1-30 mg/kg/day. Clinical arthritis scores are assessed based on paw swelling and redness. Paw thickness is measured using calipers. At study endpoint, joints are collected for histopathological analysis (H&E staining, Safranin O staining). Serum levels of inflammatory cytokines (TNF-α, IL-6, IL-1β) are measured by ELISA. Blood samples are collected for pharmacokinetic analysis. Sample sizes typically range from 8-10 animals per group. |
| ADME/Pharmacokinetics |
Poseltinib is orally bioavailable. Solubility: soluble in DMSO. Storage: dry, dark, at 0-4°C for short term (days to weeks) or -20°C for long term (months to years). The compound is supplied as a solid powder with purity ≥98%. In vivo formulation typically involves DMSO/PEG300 or similar vehicles. The compound shows favorable pharmacokinetic properties with oral administration suitable for once-daily dosing in preclinical studies.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Poseltinib are limited to preclinical studies. In animal models, the compound is generally well-tolerated at therapeutic doses (6 mg/kg/day). Standard toxicology profiling would include acute toxicity in rodents, 14-day and 28-day repeat-dose studies with histopathological examination, hematology and clinical chemistry analysis, and genotoxicity assessment. As an irreversible kinase inhibitor, potential off-target effects require careful evaluation. The compound is intended for research use only and has not received regulatory approval for clinical use.
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| References |
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| Additional Infomation |
Poseltinib is being investigated in the clinical trial NCT02628028 (LY3337641 study for the treatment of rheumatoid arthritis). Poseltinib is a Bruton's tyrosine kinase (BTK) inhibitor with potential anti-inflammatory activity. After administration, Poseltinib inhibits BTK activity and blocks the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents the activation of BTK-mediated inflammatory pathways.
Poseltinib is also known as HM71224, HM-71224, LY3337641, LY-3337641. It is a BTK inhibitor initially developed for autoimmune and inflammatory disease models, particularly rheumatoid arthritis. Unlike many BTK inhibitors that have achieved clinical success in B-cell malignancies, Poseltinib was extensively characterized in autoimmune disease models. Its unique selectivity profile among TEC family kinases establishes it as a distinct tool compound for specific scientific inquiries. No regulatory approvals have been reported for human use. |
| Molecular Formula |
C26H26N6O3
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|---|---|
| Molecular Weight |
470.5230
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| Exact Mass |
470.206
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| CAS # |
1353552-97-2
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| PubChem CID |
56644522
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
709
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C([H])=C([H])C2=C1C(=NC(=N2)N([H])C1C([H])=C([H])C(=C([H])C=1[H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])OC1=C([H])C([H])=C([H])C(=C1[H])N([H])C(C([H])=C([H])[H])=O
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| InChi Key |
LZMJNVRJMFMYQS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H26N6O3/c1-3-23(33)27-19-5-4-6-21(17-19)35-25-24-22(11-16-34-24)29-26(30-25)28-18-7-9-20(10-8-18)32-14-12-31(2)13-15-32/h3-11,16-17H,1,12-15H2,2H3,(H,27,33)(H,28,29,30)
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| Chemical Name |
N-[3-[2-[4-(4-methylpiperazin-1-yl)anilino]furo[3,2-d]pyrimidin-4-yl]oxyphenyl]prop-2-enamide
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| Synonyms |
HM-71224 LY3337641HM 71224 LY 3337641PoseltinibHM71224 LY-3337641
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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 : ~100 mg/mL (~212.53 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (15.94 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 75.0 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. Solubility in Formulation 2: ≥ 7.5 mg/mL (15.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 75.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1253 mL | 10.6265 mL | 21.2531 mL | |
| 5 mM | 0.4251 mL | 2.1253 mL | 4.2506 mL | |
| 10 mM | 0.2125 mL | 1.0627 mL | 2.1253 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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