| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
BI8626 targets HUWE1, a ubiquitin ligase (E3) that regulates the degradation of various proteins. It is a specific inhibitor with an IC₅₀ of 0.9 µM. By inhibiting HUWE1, it modulates protein degradation pathways involved in immune cell function and cholesterol metabolism.
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| ln Vitro |
In HeLa cells, BI8626 stimulates HUWE1 ectopic expression to remove MCL1 ubiquitination [1]. BI8626 has an IC50 value of 0.7 μM, which inhibits the development of Ls174T cell colonies. All phases of the cell cycle are delayed in LS174T cells by BI8622 (1-4 days) treatment, with the G1 phase being most affected [1]. In U2OS cells, BI8626 (0-50 μM; 0–6 hours) postpones MCL1 degradation in response to fast depletion to a degree similar to HUWE1 depletion.
In vitro, BI8626 inhibits HUWE1 activity with an IC₅₀ of 0.9 µM. It inhibits intracellular cholesterol. It decreases the expression of phosphorylated ZAP-70, CD25, and other activation markers. It inhibits the proliferation of CD4 T-cells. |
| ln Vivo |
In vivo, BI8626 has protective effects against spontaneous desiccation syndrome in NOD/ShiLtj mice. It has been studied for its potential in treating autoimmune diseases and immune disorders.
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| Enzyme Assay |
The in vitro enzyme assay for BI8626 measures the inhibition of HUWE1 ubiquitin ligase activity. Recombinant HUWE1 is incubated with the compound, a substrate protein, and ubiquitin in the presence of ATP. The ubiquitination of the substrate is quantified, and IC₅₀ values are calculated.
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| Cell Assay |
Cell Cycle Analysis [1]
Cell Types: Ls174T Cell Tested Concentrations: 0 μM, 5 μM, 10 μM, 15 μM, 20 μM Incubation Duration: 0-4 days Experimental Results: Ls174T cells passed all stages with delayed passage. cell cycle, among which G1 has the strongest influence. Western Blot Analysis[1] Cell Types: U2OS Cell Tested Concentrations: 0 μM, 20 μM, 50 μM Incubation Duration: 0 hrs (hours), 1 hour, 2 hrs (hours), 4 hrs (hours), 6 hrs (hours) Experimental Results: Delayed degradation of MCL1 due to UV irradiation Acts in HeLa cells by inhibiting HUWE1 in U2OS cells. In vitro cell-based assays for BI8626 are performed using immune cells, such as T cells. Cells are treated with BI8626, and cell proliferation is measured. Activation markers such as CD25 and phosphorylated ZAP-70 are assessed by flow cytometry or Western blotting. Intracellular cholesterol levels are measured. |
| Animal Protocol |
In vivo animal experiments for BI8626 have been conducted in NOD/ShiLtj mice. Animals are administered the compound, and disease progression is monitored. Immune cell infiltration and activation markers are assessed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BI8626 have been characterized in preclinical species. Detailed PK parameters such as half-life, clearance, and bioavailability are determined from plasma concentration-time profiles.
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| Toxicity/Toxicokinetics |
Toxicological data for BI8626 are limited. In standard preclinical safety assessments, it would be evaluated for potential off-target effects and general toxicity. The compound is intended for research use only and not for therapeutic use in humans.
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| References | |
| Additional Infomation |
BI8626 is a specific HUWE1 inhibitor that has been studied for its potential in treating autoimmune diseases. It has protective effects against spontaneous desiccation syndrome in a mouse model. It has not been approved for clinical use.
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| Molecular Formula |
C25H28N8
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|---|---|
| Molecular Weight |
440.543423652649
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| Exact Mass |
440.243
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| CAS # |
1875036-75-1
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| PubChem CID |
138377589
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.3
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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 |
33
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| Complexity |
577
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(CC2C=CC=CC=2)CCN(C2C3C(=C(N=CN=3)NCC3C=CC=C(CN)C=3)N=CN=2)CC1
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| InChi Key |
DZDNGSNKWIORRZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H28N8/c26-14-20-7-4-8-21(13-20)15-27-24-22-23(29-17-30-24)25(31-18-28-22)33-11-9-32(10-12-33)16-19-5-2-1-3-6-19/h1-8,13,17-18H,9-12,14-16,26H2,(H,27,29,30)
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| Chemical Name |
N-(3-(Aminomethyl)benzyl)-8-(4-benzylpiperazin-1-yl)pyrimido[5,4-d]pyrimidin-4-amine
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| Synonyms |
BI8626; BI 8626; BI-8626
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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 : ~83.33 mg/mL (~189.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.72 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 (4.72 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 20.8 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 | 2.2699 mL | 11.3497 mL | 22.6994 mL | |
| 5 mM | 0.4540 mL | 2.2699 mL | 4.5399 mL | |
| 10 mM | 0.2270 mL | 1.1350 mL | 2.2699 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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