INCB059872 is a potent, orally bioactive, selective and irreversible lysine-specific demethylase 1 (LSD1) inhibitor. INCB059872 may be utilized in the research of myeloid leukemia.

Physicochemical Properties

Molecular Formula	C23H34N2O3
Molecular Weight	386.53
Exact Mass	386.256
CAS #	1802909-49-4
Related CAS #	INCB059872 dihydrochloride
PubChem CID	118290753
Appearance	Off-white to light yellow solid powder
LogP	0.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	9
Heavy Atom Count	28
Complexity	534
Defined Atom Stereocenter Count	2
SMILES	C1(CN2CCC(COC)(CN[C@@H]3C[C@H]3C3=CC=CC=C3)CC2)(C(O)=O)CCC1
InChi Key	WBPWDDPSYSUQJA-VQTJNVASSA-N
InChi Code	InChI=1S/C23H34N2O3/c1-28-17-22(15-24-20-14-19(20)18-6-3-2-4-7-18)10-12-25(13-11-22)16-23(21(26)27)8-5-9-23/h2-4,6-7,19-20,24H,5,8-17H2,1H3,(H,26,27)/t19-,20+/m0/s1
Chemical Name	1-[[4-(methoxymethyl)-4-[[[(1R,2S)-2-phenylcyclopropyl]amino]methyl]piperidin-1-yl]methyl]cyclobutane-1-carboxylic acid
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)

Biological Activity

Targets	KDM1/LSD1
ln Vitro	In 293T cells, INCB059872 (25 nM; 48 h) upregulates both enhancer activity and gene expression[1]. THP-1 cells exposed to INCB059872 (25 nM; 24 hours) exhibit a growth deficiency after one cell doubling time, or roughly three days. Genes and enhancers are identified by PRO-seq analysis, which is regulated by INCB059872 (THP-1 cells)[1].
ln Vivo	Incb059872 (10 mg/kg; po; 0, 4, or 6 days; C57BL/6J mice) performs single-cell RNA-seq analysis that reveals variations in the populations of bone marrow progenitor[1].
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.
Animal Protocol	Animal/Disease Models: 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.
References	[1]. Nascent transcript and single-cell RNA-seq analysis defines the mechanism of action of the LSD1 inhibitor INCB059872 in myeloid leukemia. Gene. 2020;752:144758.
Additional Infomation	Lysine-specific Demethylase 1 Inhibitor INCB059872 is an orally available inhibitor of lysine-specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, INCB059872 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4, respectively, through amine oxidation. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes. Altogether, this may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, an enzyme belonging to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family, is overexpressed in certain tumor cells and plays a key role in the regulation of gene expression and in tumor cell growth and survival.

Solubility Data

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5871 mL	12.9356 mL	25.8712 mL
	5 mM	0.5174 mL	2.5871 mL	5.1742 mL
	10 mM	0.2587 mL	1.2936 mL	2.5871 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.