| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
KDM1/LSD1
The primary target of INCB059872 dihydrochloride is LSD1/KDM1A, an epigenetic enzyme that demethylates mono- and di-methylated histone H3. By irreversibly inhibiting LSD1, this compound increases the levels of H3K4me1/2 and H3K9me1/2, leading to reactivation of tumor suppressor genes and differentiation of malignant cells in acute myeloid leukemia (AML) and other hematologic malignancies. |
|---|---|
| ln Vitro |
INCB059872 (293T cells; 48 hours; 25 nM) Dihydrochloride elevates gene expression and enhancer activity [1]. INCB059872 (THP-1 cells; 25 nM; 48 hours) THP-1 shows a growth deficiency when exposed to dihydrochloride after one cell doubling time, or roughly three days [1]. Dihydrochloride of INCB059872 (THP-1 cells) modifies genes and enhancers found using PRO-seq research [1].
In cell-free LSD1 demethylase assays, INCB059872 dihydrochloride inhibits LSD1 activity with low nanomolar IC50 values. The compound binds covalently to the FAD cofactor of LSD1, resulting in irreversible inhibition. It exhibits high selectivity over other histone demethylases (e.g., LSD2/KDM1B) and monoamine oxidases (MAO-A and MAO-B). |
| ln Vivo |
Single-cell RNA-seq reveals myeloid progenitor cell populations; INCB059872 (10 mg/kg; po; 0, 4, or 6 days; C57BL/6J mice) dihydrochloride facilitates this process [1].
In AML cell lines (e.g., THP-1, MV4-11, Kasumi-1), INCB059872 dihydrochloride induces differentiation, as shown by increased CD11b and CD14 surface markers, and suppresses proliferation with IC50 values in the low nanomolar range. The compound also reduces clonogenic growth in colony-forming assays and induces apoptosis in sensitive cell lines. |
| Enzyme Assay |
The inhibitory activity of INCB059872 dihydrochloride against LSD1 is measured using a cell-free demethylase assay. Recombinant LSD1 protein is incubated with a biotinylated H3K4me2 peptide substrate in the presence of varying concentrations of the test compound. After reaction, the amount of demethylated product is quantified by ELISA using a specific antibody against H3K4me1. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: 293T cells Tested Concentrations: 250 nM Incubation Duration: 48 hrs (hours) Experimental Results: Increased enhancer activity and gene expression. Leukemia cell lines (e.g., THP-1, MV4-11, Kasumi-1) are cultured in RPMI-1640 medium supplemented with 10% FBS. Cells are treated with INCB059872 dihydrochloride (0.1-1000 nM) for 3-7 days. Cell viability is assessed using CellTiter-Glo or MTS assays. Differentiation is measured by flow cytometry using CD11b-PE and CD14-FITC antibodies. Apoptosis is evaluated by Annexin V/PI staining. All experiments are performed in triplicate. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J mice[1]
Doses: 10 mg/kg Route of Administration: po; 0, 4, or 6 days Experimental Results: Single-cell RNA-seq revealed changes in bone marrow progenitor populations. In a mouse xenograft model of AML, INCB059872 dihydrochloride is administered orally at doses of 10-30 mg/kg once daily for 21-28 days. Tumor growth is measured by bioluminescence imaging or caliper measurement. The compound significantly reduces tumor burden and prolongs survival compared to vehicle controls. Immunohistochemical analysis of tumor tissues shows increased H3K4me2 staining and decreased Ki67-positive cells. |
| ADME/Pharmacokinetics |
INCB059872 dihydrochloride is orally bioavailable, with good absorption and systemic exposure in preclinical species. In rats and mice, the compound reaches peak plasma concentrations within 1-2 hours after oral administration. The terminal half-life ranges from 4-8 hours, supporting once-daily dosing. Metabolism occurs primarily via CYP450 enzymes, and the compound is excreted in both urine and feces.
|
| Toxicity/Toxicokinetics |
In preclinical toxicology studies, INCB059872 dihydrochloride is well-tolerated at doses up to 30 mg/kg in rats and mice. No significant adverse effects on body weight, food consumption, or clinical pathology parameters are observed at therapeutic doses. Mild thrombocytopenia and gastrointestinal effects are noted at higher doses. No target organ toxicity is evident in histopathological examinations.
|
| References | |
| Additional Infomation |
INCB059872 dihydrochloride is a research compound that has been evaluated in clinical trials for the treatment of acute myeloid leukemia (AML) and other hematologic malignancies. The compound represents a promising epigenetic therapy targeting LSD1. As of the latest information, it remains in clinical development and is not yet approved for routine clinical use.
|
| Molecular Formula |
C23H36CL2N2O3
|
|---|---|
| Molecular Weight |
459.45
|
| Related CAS # |
INCB059872;1802909-49-4
|
| Appearance |
White to light yellow solid powder
|
| 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 Note: Please store this product in a sealed and protected environment, 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)
|
| Solubility (In Vitro) |
DMSO :~3.57 mg/mL (~7.77 mM)
|
|---|---|
| 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 | 2.1765 mL | 10.8826 mL | 21.7652 mL | |
| 5 mM | 0.4353 mL | 2.1765 mL | 4.3530 mL | |
| 10 mM | 0.2177 mL | 1.0883 mL | 2.1765 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
