| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary target is the PWWP1 domain of NSD3 (nuclear receptor-binding SET domain 3). BI-9321 binds to the PWWP1 domain with a Kd of 166 nM and acts as an antagonist, disrupting its interaction with methylated histones. This inhibits NSD3-mediated chromatin modification and gene expression. BI-9321 is selective for NSD3-PWWP1 over NSD2-PWWP1 and NSD3-PWWP2.
|
|---|---|
| ln Vitro |
At 1 µM concentration, BI-9321 demonstrates submicromolar in vitro activity and cellular target engagement, specifically targeting the methyllysine binding region of the PWWP1 domain. BI-9321, when used alone, inhibits the production of Myc messenger RNA and decreases MOLM-13 cell growth [1].
In vitro activity is evaluated through binding assays. The binding affinity of BI-9321 to the NSD3-PWWP1 domain is measured using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC), yielding a Kd of 166 nM. The compound's effect on NSD3-mediated histone methylation is assessed using biochemical assays with recombinant nucleosomes. |
| ln Vivo |
In vivo activity is manifested through the biological effects of NSD3-PWWP1 inhibition. In cancer models where NSD3 is amplified or overexpressed (e.g., lung cancer, breast cancer), BI-9321 inhibits tumor cell proliferation and induces apoptosis. The compound's pharmacokinetic properties and toxicity are evaluated.
|
| Enzyme Assay |
The non-cellular binding assay involves measuring the binding of BI-9321 to the NSD3-PWWP1 domain using SPR or ITC. The Kd value is determined. The compound's ability to compete with a methylated histone peptide for binding to the PWWP1 domain is assessed using fluorescence polarization.
|
| Cell Assay |
Cell-based assays involve treating cancer cell lines (e.g., H3122, A549) with BI-9321 at varying concentrations. Cell viability is measured by MTT or CCK-8 assay. The compound's effect on NSD3 target gene expression is assessed by quantitative RT-PCR. Apoptosis is assessed by flow cytometry.
|
| Animal Protocol |
In vivo animal experiments involve administering BI-9321 to tumor-bearing mice via oral gavage or intraperitoneal injection. Doses range from 1-50 mg/kg. Tumor growth is monitored by measuring tumor volume. Tumor tissue is analyzed by immunohistochemistry for proliferation markers (e.g., Ki-67) and apoptosis markers (e.g., cleaved caspase-3).
|
| References |
[1]. Böttcher J, et al. Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3. Nat Chem Biol. 2019 Aug;15(8):822-829.
|
| Additional Infomation |
Selective antagonists of the NSD3-PWWP1 domain
|
| Molecular Formula |
C22H21FN4
|
|---|---|
| Molecular Weight |
360.43
|
| Exact Mass |
360.175
|
| CAS # |
2387510-86-1
|
| Related CAS # |
BI-9321 trihydrochloride;2387510-87-2
|
| PubChem CID |
138115329
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
3.3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
27
|
| Complexity |
491
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC(=CC(=C1C2=C(N(C=N2)C)C3=C4C=CC(=CC4=NC=C3)F)C)CN
|
| InChi Key |
WOAOENGFAAUUGT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H21FN4/c1-13-8-15(11-24)9-14(2)20(13)21-22(27(3)12-26-21)18-6-7-25-19-10-16(23)4-5-17(18)19/h4-10,12H,11,24H2,1-3H3
|
| Chemical Name |
[4-[5-(7-fluoroquinolin-4-yl)-1-methylimidazol-4-yl]-3,5-dimethylphenyl]methanamine
|
| Synonyms |
BI9321; BI 9321
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7745 mL | 13.8723 mL | 27.7446 mL | |
| 5 mM | 0.5549 mL | 2.7745 mL | 5.5489 mL | |
| 10 mM | 0.2774 mL | 1.3872 mL | 2.7745 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
