GSK3735967 is a selective, reversible, non-nucleoside DNMT1 inhibitor. GSK3735967 contains a planar dicyanopyridine core that specifically embeds into DNMT1-bound hemimethylated CpG dinucleotides. GSK3735967 has three binding sites, one of which can bind to histone H4K20me3.

Physicochemical Properties

Molecular Formula	C25H31N7OS
Molecular Weight	477.62494301796
Exact Mass	477.231
CAS #	2170136-86-2
PubChem CID	132233120
Appearance	Off-white to yellow solid powder
LogP	2.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	8
Heavy Atom Count	34
Complexity	753
Defined Atom Stereocenter Count	0
SMILES	C(NCC1=CC=C(CSC2=NC(N3CCCN(C)CC3)=C(C#N)C(CC)=C2C#N)C=C1)(=O)CN
InChi Key	QPLFMVVUDGWTPG-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H31N7OS/c1-3-20-21(13-26)24(32-10-4-9-31(2)11-12-32)30-25(22(20)14-27)34-17-19-7-5-18(6-8-19)16-29-23(33)15-28/h5-8H,3-4,9-12,15-17,28H2,1-2H3,(H,29,33)
Chemical Name	2-amino-N-[[4-[[3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl]sulfanylmethyl]phenyl]methyl]acetamide
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 a dose-dependent manner, GSK3735967 (0.1–1000 nM) suppresses DNMT1 activity [1].
References	[1]. Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors. Structure. 2022 Jun 2;30(6):793-802.e5. [2]. Structural Studies of DNMT1-DNA Complexes with a Reversible Series of Dicyanopyridine Containing Selective, Non-Nucleoside Inhibitors. Foundations of Crystallography, 2022, 78: a246.

Solubility Data

Solubility (In Vitro)

DMSO : 31.25 mg/mL (65.43 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.35 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 20.8 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: 2.08 mg/mL (4.35 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.35 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 20.8 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	2.0937 mL	10.4686 mL	20.9371 mL
	5 mM	0.4187 mL	2.0937 mL	4.1874 mL
	10 mM	0.2094 mL	1.0469 mL	2.0937 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.