| 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 |
TAK1 (MAP3K7). HS-276 is a highly selective TAK1 inhibitor with a Ki of 2.5 nM and IC50 of 8.25 nM. It also inhibits CLK2 (IC50=29 nM), GCK (IC50=22 nM), ULK2 (IC50=63 nM), MAP4K5 (IC50=125 nM), IRAK1 (IC50=264 nM), NUAK (IC50=270 nM), CSNK1G2 (IC50=810 nM), CAMKKbeta-1 (IC50=1280 nM), and MLK1 (IC50=5585 nM).
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| ln Vitro |
With IC50 values of 138, 201, and 234 nM, respectively, HS-276 decreases TNF, IL-6, and IL-1β expression in a dose-dependent manner [1].
HS-276 (IC50=8.25 nM) shows significant inhibition of TAK1-mediated signaling pathways. The compound has been evaluated for its ability to inhibit TNF-mediated cytokine profiles in vitro with an IC50 of 138 nM. This in vitro activity correlates with anti-inflammatory effects in disease models. HS-276 demonstrates high selectivity for TAK1 over other kinases at relevant concentrations. |
| ln Vivo |
Inflammation, pannus, cartilage destruction (CD), bone resorption (BR), and periosteal bone formation (PBF) are all decreased by HS-276 (a CIA mouse model of inflammatory arthritis, administered 50 mg/kg, IP, daily for 6 days) Histological findings [1]. With a Cmax of 3.68 μM and a %F of 98.1%, HS-276 (CD-1 mice, 30 mg/kg, oral gavage once) demonstrates good bioavailability in mice [1].
HS-276 demonstrated significant attenuation of arthritic-like symptoms in the collagen-induced arthritis (CIA) mouse model of inflammatory RA. The compound is orally bioavailable and has shown in vivo efficacy in this model, correlating with its inhibition of TNF-mediated cytokine profiles. Detailed dosing regimens are provided in the literature. |
| Enzyme Assay |
Not explicitly detailed in reference sources. A typical TAK1 binding assay involves incubating recombinant TAK1 protein with HS-276 and a fluorescent tracer in a buffer system, then measuring binding affinity using fluorescence polarization (FP) or TR-FRET. The Ki value of 2.5 nM was determined using such methods in biochemical kinase assays.
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| Cell Assay |
Not explicitly detailed in reference sources. A standard cellular assay for TAK1 inhibition involves treating cells with TNFalpha to activate TAK1 signaling, then measuring downstream NF-kappaB activation or cytokine production. HS-276 would be added to cells 1 hour prior to TNFalpha stimulation. Phosphorylation of TAK1 substrates is detected by Western blot.
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| Animal Protocol |
In the collagen-induced arthritis (CIA) mouse model, HS-276 is administered orally at doses ranging from 1-30 mg/kg daily starting from the onset of arthritis symptoms. Disease progression is monitored by clinical scoring of paw swelling, measurement of paw thickness, and histological analysis of joint inflammation and bone erosion.
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| ADME/Pharmacokinetics |
HS-276 is orally bioavailable with a molecular weight of 419.53 and formula C24H29N5O2. It is soluble in DMSO (45 mg/mL, 107.3 mM). For in vivo oral administration, HS-276 can be formulated in CMC-Na solution (≥5 mg/mL). For intravenous injection, a formulation of 5% DMSO + 40% PEG300 + 5% Tween80 + 50% ddH2O can be used.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for HS-276 are provided in the reference sources. In the collagen-induced arthritis mouse model, HS-276 is reported to be well-tolerated at the tested doses. However, comprehensive safety pharmacology and toxicology studies would be required for clinical development. The compound is for research use only.
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| References | |
| Additional Infomation |
HS-276 is a research compound not yet approved for clinical use. It has been developed as a selective TAK1 inhibitor for the potential treatment of inflammatory arthritis and other TAK1-mediated inflammatory diseases. The compound shows good oral bioavailability, selectivity over other kinases, and in vivo efficacy in RA models.
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| Molecular Formula |
C24H29N5O2
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|---|---|
| Molecular Weight |
419.52
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| Exact Mass |
419.232
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| CAS # |
2767422-72-8
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| PubChem CID |
164517032
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
623
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C(NC2N(CCC)C3=CC(CN4CCCCC4)=CC=C3N=2)=O)=CC=CC(C(N)=O)=C1
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| InChi Key |
NPEMHKSMWPZEOV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H29N5O2/c1-2-11-29-21-14-17(16-28-12-4-3-5-13-28)9-10-20(21)26-24(29)27-23(31)19-8-6-7-18(15-19)22(25)30/h6-10,14-15H,2-5,11-13,16H2,1H3,(H2,25,30)(H,26,27,31)
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| Chemical Name |
3-N-[6-(piperidin-1-ylmethyl)-1-propylbenzimidazol-2-yl]benzene-1,3-dicarboxamide
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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 : ~50 mg/mL (~119.18 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.96 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 25.0 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: ≥ 2.5 mg/mL (5.96 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3837 mL | 11.9184 mL | 23.8368 mL | |
| 5 mM | 0.4767 mL | 2.3837 mL | 4.7674 mL | |
| 10 mM | 0.2384 mL | 1.1918 mL | 2.3837 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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