| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
BI-9321 triHCl targets the NSD3-PWWP1 domain, a methyl-lysine binding domain of the nuclear receptor-binding SET domain protein 3 (NSD3). NSD3 is a histone methyltransferase that plays important roles in chromatin regulation, gene expression, and cancer development. The PWWP domain of NSD3 recognizes methylated histones and mediates the recruitment of NSD3 to specific chromatin regions. BI-9321 triHCl binds to the methyl-lysine binding site of the NSD3-PWWP1 domain with submicromolar in vitro activity. The compound shows high selectivity for NSD3-PWWP1 over NSD2-PWWP1 and NSD3-PWWP2. By inhibiting NSD3-PWWP1, the compound modulates gene expression, including increasing MYC mRNA expression.
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| ln Vitro |
The BI-9321 triHClide domain's methyl-lysine binding site exhibits submicromolar in vitro activity and 1 μM cellular target binding. When used alone, BI-9321 triHClide inhibits MOLM-13 cell growth and increases the expression of Myc messenger RNA [1].
In vitro, BI-9321 triHCl binds to the NSD3-PWWP1 domain with a Kd of 166 nM as determined by surface plasmon resonance (SPR). The compound demonstrates submicromolar in vitro activity at the methyl-lysine binding site. In cellular assays, BI-9321 triHCl achieves 1 μM cellular target binding. When used alone, the compound inhibits MOLM-13 cell growth and increases the expression of MYC messenger RNA. The compound's selectivity for NSD3-PWWP1 over NSD2-PWWP1 and NSD3-PWWP2 makes it a valuable tool for studying NSD3 biology and developing epigenetic therapies. The compound is soluble in water and DMSO at 100 mM. |
| ln Vivo |
In vivo, BI-9321 triHCl has not been extensively reported in the available literature. As an inhibitor of the NSD3-PWWP1 domain, the compound would be expected to modulate gene expression and potentially inhibit tumor growth in animal models. NSD3 is implicated in various cancers, including leukemia, and targeting the PWWP domain represents a novel therapeutic strategy. The compound's ability to inhibit MOLM-13 cell growth in vitro suggests potential efficacy in leukemia models. However, detailed in vivo efficacy, pharmacokinetic, and toxicological data for BI-9321 triHCl require further investigation from primary research publications. The compound is supplied as a research chemical for epigenetic research.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cellular) assays for BI-9321 triHCl involve measuring binding affinity to the NSD3-PWWP1 domain using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). In SPR assays, the recombinant NSD3-PWWP1 protein is immobilized on a sensor chip, and varying concentrations of BI-9321 triHCl are flowed over the chip. The binding response is measured in real-time, and the dissociation constant (Kd) is calculated from the binding curves. The compound binds to the NSD3-PWWP1 domain with a Kd of 166 nM. Selectivity profiling against NSD2-PWWP1 and NSD3-PWWP2 confirms the compound's specificity. Fluorescence polarization or AlphaScreen assays may also be used to assess binding affinity.
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| Cell Assay |
In vitro cellular experiments with BI-9321 triHCl are performed using MOLM-13 acute myeloid leukemia cells or other cancer cell lines. Cells are cultured in appropriate medium (e.g., RPMI 1640 with 10% FBS) and treated with varying concentrations of the compound for 24-72 hours. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. Target engagement is confirmed by measuring the expression of MYC messenger RNA using RT-qPCR. The compound's effects on cell cycle, apoptosis, and other signaling pathways may also be assessed. Cells are maintained at 37°C in 5% CO₂ with appropriate media supplements.
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| Animal Protocol |
In vivo animal studies with BI-9321 triHCl have not been extensively reported. For leukemia models, standard in vivo studies include xenografts of MOLM-13 or other AML cell lines in immunocompromised mice (e.g., NSG or NOD/SCID mice). Mice are injected with AML cells via tail vein or subcutaneous implantation, and after tumor establishment, treated with BI-9321 triHCl via oral, intraperitoneal, or intravenous administration at various doses and schedules. Efficacy is assessed by measuring tumor burden (bioluminescence imaging, flow cytometry for human CD45⁺ cells in bone marrow and blood), survival rates, and histopathological examination of bone marrow, spleen, and liver. Pharmacodynamic markers such as MYC mRNA expression may be measured to confirm target engagement.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BI-9321 triHCl are not extensively characterized. The compound has molecular formula C₂₂H₂₄Cl₃FN₄ and molecular weight 469.81. It is supplied as a trihydrochloride salt with purity ≥98% and is soluble in water and DMSO at 100 mM. As a small molecule (molecular weight 469.81) with good aqueous solubility, it is expected to have reasonable oral bioavailability and tissue distribution. Storage recommendations: desiccate at room temperature. Detailed pharmacokinetic parameters including half-life, clearance, and bioavailability require further investigation from primary research publications.
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| Toxicity/Toxicokinetics |
Toxicological information for BI-9321 triHCl is not extensively detailed in the available literature. As a research compound with epigenetic activity, it should be handled with appropriate safety precautions. Standard safety guidelines for handling potent pharmaceutical compounds apply, including use of personal protective equipment (gloves, safety goggles, lab coat), working in a well-ventilated area, and proper chemical waste disposal. The compound is intended for research use only and is not approved for human therapeutic use. Cytotoxicity studies in cell-based assays help establish the therapeutic window and selectivity index of the compound.
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| References | |
| Additional Infomation |
BI-9321 triHCl (CAS 2387510-87-2) is a potent, selective, and cellularly active antagonist (inhibitor) of the NSD3-PWWP1 domain. The compound has molecular formula C₂₂H₂₄Cl₃FN₄ and molecular weight 469.81. BI-9321 triHCl binds to the NSD3-PWWP1 domain with a Kd of 166 nM as determined by surface plasmon resonance (SPR). The compound is not effective against NSD2-PWWP1 or NSD3-PWWP2. When used alone, BI-9321 triHCl inhibits MOLM-13 cell growth and increases the expression of MYC messenger RNA. The compound is supplied as a trihydrochloride salt with purity ≥98% and is soluble in water and DMSO at 100 mM. Storage: desiccate at room temperature.
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| Molecular Formula |
C22H24CL3FN4
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| Molecular Weight |
469.810165405273
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| Exact Mass |
468.105
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| CAS # |
2387510-87-2
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| Related CAS # |
BI-9321;2387510-86-1
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| PubChem CID |
145874876
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
491
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.Cl.FC1C=CC2C(C=1)=NC=CC=2C1=C(C2C(C)=CC(CN)=CC=2C)N=CN1C
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| InChi Key |
DCDXMBVQCRHZMW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21FN4.3ClH/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;3*1H
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| Chemical Name |
[4-[5-(7-fluoroquinolin-4-yl)-1-methylimidazol-4-yl]-3,5-dimethylphenyl]methanamine;trihydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~250 mg/mL (~532.13 mM)
H2O : ~25 mg/mL (~53.21 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 25 mg/mL (53.21 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 250.0 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: ≥ 25 mg/mL (53.21 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 250.0 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. View More
Solubility in Formulation 3: ≥ 25 mg/mL (53.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (212.85 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1285 mL | 10.6426 mL | 21.2852 mL | |
| 5 mM | 0.4257 mL | 2.1285 mL | 4.2570 mL | |
| 10 mM | 0.2129 mL | 1.0643 mL | 2.1285 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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