Description: UNC0379 is a substrate competitive lysine methyltransferase SETD8 (KMT5A) inhibitor with antineoplastic activity. It inhibits KMT5A with an IC50 of 7.9 μM, and shows higher selectivity for KMT5A over 15 other methyltransferases.

Physicochemical Properties

Molecular Formula	C23H35N5O2
Molecular Weight	413.56
Exact Mass	413.279
CAS #	1620401-82-2
Related CAS #	UNC0379 TFA;1620401-83-3
PubChem CID	78357767
Appearance	Off-white to yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	606.3±65.0 °C at 760 mmHg
Flash Point	320.5±34.3 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.606
LogP	2.76
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	10
Heavy Atom Count	30
Complexity	498
Defined Atom Stereocenter Count	0
InChi Key	WEXCGGWTIDNVNT-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H35N5O2/c1-29-20-16-18-19(17-21(20)30-2)25-23(28-14-8-9-15-28)26-22(18)24-10-4-3-5-11-27-12-6-7-13-27/h16-17H,3-15H2,1-2H3,(H,24,25,26)
Chemical Name	6,7-dimethoxy-2-pyrrolidin-1-yl-N-(5-pyrrolidin-1-ylpentyl)quinazolin-4-amine
Synonyms	UNC-0379, UNC 0379, UNC0379
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	UNC0379 (1–10 μM, 9 days) prevents the growth of HGSOC cells[2]. UNC0379 (10 μM, 96 h) causes an increase in the percentage of HGSOC cells in the sub-G1 phase[2]. Myofibroblast de-differentiation is induced and further fibroblast to myofibroblast differentiation is inhibited by UNC0379 (10 μM, 96 h) 48 h][3].
ln Vivo	In mice with lung fibrosis induced by bleomycin (BLM), UNC0379 (intratracheal administration, 1 mg/kg/day, on days 7, 8, and 9) ameliorates the lung fibrosis[3].
Cell Assay	Cell Viability Assay[1] Cell Types: JHOS2, JHOS3, JHOS4, OVCAR3, OVCAHO, OVKATE, KURAMOCHI, TYKnu Tested Concentrations: 1-10 μM Incubation Duration: 9 days Experimental Results: Inhibited HGSOC cells proliferation with IC50s ranging from 0.39 to 3.20 µM. Cell Cycle Analysis[1] Cell Types: JHOS3, OVCAR3 Tested Concentrations: 10 µM Incubation Duration: 96 h Experimental Results: Arrested cells in sub-G1 phase.
Animal Protocol	Animal/Disease Models: Bleomycin (BLM)-induced lung fibrosis mouse model[3] Doses: 1 mg/kg/day Route of Administration: Intracheal administration, on day7, 8, and 9. Experimental Results: Ameliorated BLM-induced lung fibrosis (supported by the evaluation of the Ashcroft score and changes in the collagen content in the lung samples) without affecting pulmonary inflammation.
References	[1]. Discovery of a Selective, Substrate-Competitive Inhibitor of the Lysine Methyltransferase SETD8. J Med Chem. 2014 Aug 14;57(15):6822-33. [2]. Epigenetic Modifier SETD8 as a Therapeutic Target for High-Grade Serous Ovarian Cancer. Biomolecules. 2020 Dec 16;10(12):1686. [3]. Inhibition of the SET8 Pathway Ameliorates Lung Fibrosis Even Through Fibroblast Dedifferentiation. Front Mol Biosci. 2020 Aug 5;7:192.

Solubility Data

Solubility (In Vitro)

DMSO:Soluble in DMSO Water: N/A Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.05 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 (6.05 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 (6.05 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	2.4180 mL	12.0901 mL	24.1803 mL
	5 mM	0.4836 mL	2.4180 mL	4.8361 mL
	10 mM	0.2418 mL	1.2090 mL	2.4180 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.