WSF1-IN-1 (compound 136) is an orally bioactive WSF1 inhibitor that may be utilized in tumor research related to the Wolfram syndrome gene WSF1. Its IC50 is 0.33 in the HepG2 maternal cell line and the HepG2 WFS1 KO cell line respectively. μM and >27 μM.

Physicochemical Properties

Molecular Formula	C20H21F3N8O
Molecular Weight	446.43
Exact Mass	446.179
CAS #	2379577-82-7
PubChem CID	146194099
Appearance	White to off-white solid powder
LogP	2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	5
Heavy Atom Count	32
Complexity	667
Defined Atom Stereocenter Count	1
SMILES	C[C@H]1C(=O)NC2=C(N=C(N=C2N1C)NCC3=CN(N=C3)CC4=CN=C(C=C4)C(F)(F)F)C
InChi Key	KKHCZENFFDIZHM-LBPRGKRZSA-N
InChi Code	InChI=1S/C20H21F3N8O/c1-11-16-17(30(3)12(2)18(32)28-16)29-19(27-11)25-7-14-8-26-31(10-14)9-13-4-5-15(24-6-13)20(21,22)23/h4-6,8,10,12H,7,9H2,1-3H3,(H,28,32)(H,25,27,29)/t12-/m0/s1
Chemical Name	(7S)-4,7,8-trimethyl-2-[[1-[[6-(trifluoromethyl)pyridin-3-yl]methyl]pyrazol-4-yl]methylamino]-5,7-dihydropteridin-6-one
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	WSF1-IN-1 (compound 136) has IC50 values of >27 μM and 0.03 μM for the Hek293 WFS1 over-expressor and empty vector, respectively. The IC50 values for cell valiablity of WSF1-IN-1 (compound 136) are 0.05 μM (Colo-205 Control shRNA), >9 μM (Colo-205 WSF1 shRNA), 0.08 μM (DU4415 Control shRNA), 6.1 μM (DU4415 WSF1 shRNA), 0.26 μM (HepG2 Control shRNA), and 2.2 μM (HepG2 WSF1 shRNA), respectively[1].
ln Vivo	In NSCLC-derived patient xenograft OD33996 nu/nu mice, WSF1-IN-1 (compound 136, 100 mpk qd, orally, 14 days) shows 106.65% tumor growth inhibition (TGI)[1].
References	[1]. Lauffer, David J, et al. Preparation of pyridine compass. for the treatment of cellular proliferative disorders. US 20190322673 A1.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (224.00 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.60 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 (5.60 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	2.2400 mL	11.2000 mL	22.3999 mL
	5 mM	0.4480 mL	2.2400 mL	4.4800 mL
	10 mM	0.2240 mL	1.1200 mL	2.2400 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.