UNC-926 is a potent and selective inhibitor of the L3MBTL1 (Lethal(3)malignant brain tumor-like protein) domain (Kd = 3.9 μM), which is a methyl-lysine (Kme) reader domain. UNC-926 acts by binding to the MBT domain of the L3MBTL1 protein. In a peptide pull down assay, UNC-926 was found to be able to selectively inhibits the L3MBTL1_3XMBT-H4K20me1 interaction.

Physicochemical Properties

Molecular Formula	C16H21BRN2O
Molecular Weight	337.25
Exact Mass	336.084
Elemental Analysis	C, 56.98; H, 6.28; Br, 23.69; N, 8.31; O, 4.74
CAS #	1184136-10-4
Related CAS #	UNC926 hydrochloride;1782573-49-2
PubChem CID	61041645
Appearance	White to off-white solid powder
LogP	3.025
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Heavy Atom Count	20
Complexity	335
Defined Atom Stereocenter Count	0
SMILES	O=C(C1=CC=CC(Br)=C1)N2CCC(N3CCCC3)CC2
InChi Key	OWGLFIKZKQOYHZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H21BrN2O/c17-14-5-3-4-13(12-14)16(20)19-10-6-15(7-11-19)18-8-1-2-9-18/h3-5,12,15H,1-2,6-11H2
Chemical Name	(3-Bromophenyl)[4-(1-pyrrolidinyl)-1-piperidinyl]methanone
Synonyms	UNC926 free base; UNC 926 free base; UNC-926 free base; UNC-926; UNC926; UNC 926
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

ln Vitro	In addition, UNC926 shows no binding to CBX7 and a low micromolar affinity (IC50 of 3.2 μM) for the near homolog L3MBTL3 along with a decrease in affinity for the other MBT domains[1]. UNC926 (1–25 μM) prevents the 3xMBT domain from attaching to H4K20me1. In a dose-dependent way, UNC926 prevents L3MBTL13xMBT from interacting with the relevant histonepeptides. The fact that UNC926 has no effect on 53BP1's binding to H4K20me1 indicates that it is more selective for L3MBTL1 than 53BP1[1].
ln Vivo
Animal Protocol
References	[1]. Structure–activity relationships of methyl-lysine reader antagonists. MedChemComm. 2012;3(45):45–51.

Solubility Data

Solubility (In Vitro)

DMSO:67 mg/mL (198.7 mM) Water:< 1mg/mL Ethanol:2 mg/mL (5.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.41 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 25.0 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: ≥ 2.5 mg/mL (7.41 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 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.41 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 25.0 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	2.9652 mL	14.8258 mL	29.6516 mL
	5 mM	0.5930 mL	2.9652 mL	5.9303 mL
	10 mM	0.2965 mL	1.4826 mL	2.9652 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.