DS-437 (DS437) is a novel and potent dual PRMT5 and PRMT7 inhibitor with anticancer activity. It inhibits PRMT5/7 with IC50 of 6.0 uM, and is inactive against 29 other human protein-, DNA-, and RNA-methyltransferases.

Physicochemical Properties

Molecular Formula	C15H23N7O4S
Molecular Weight	397.45
Exact Mass	397.153
CAS #	1674364-87-4
PubChem CID	122178085
Appearance	Light brown to brown solid powder
Density	1.7±0.1 g/cm3
Index of Refraction	1.776
LogP	0.16
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	7
Heavy Atom Count	27
Complexity	505
Defined Atom Stereocenter Count	4
SMILES	CCNC(=O)NCCSC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=NC3=C(N=CN=C32)N)O)O
InChi Key	CACMCLIHCDTJHL-IDTAVKCVSA-N
InChi Code	InChI=1S/C15H23N7O4S/c1-2-17-15(25)18-3-4-27-5-8-10(23)11(24)14(26-8)22-7-21-9-12(16)19-6-20-13(9)22/h6-8,10-11,14,23-24H,2-5H2,1H3,(H2,16,19,20)(H2,17,18,25)/t8-,10-,11-,14-/m1/s1
Chemical Name	1-[2-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]ethyl]-3-ethylurea
Synonyms	DS437 DS 437 DS-437
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	At equilibrium conditions (cofactor and substrate concentrations fixed at respective Km values), DS-437 can block the PRMT5-MEP50 complex's ability to methylate H4[1-24] peptide in a dose-dependent manner [1]. Its IC50 value is 5.9 ± 1.4 μM. The levels of CD8+ PD-1+ and total CD8+ T cells are raised by DS-437 [2].
ln Vivo	There are some advantageous benefits of DS-437 (10 mg/kg; i.p.; 5 times weekly) on tumor growth inhibition. A more notable result was seen when DS-437 and anti-p185erbB2/neu antibody 4D5 were combined [1].
Animal Protocol	Animal/Disease Models: Six to Ten weeks old female balb/c (Bagg ALBino) mouse (bearing CT26Her2 tumor cells)[1] Doses: 10 mg/kg Route of Administration: ip; 5 times a week Experimental Results: Had some beneficial effects on inhibiting tumor growth.
References	[1]. Discovery of a Dual PRMT5-PRMT7 Inhibitor.ACS Med Chem Lett. 2015 Mar 2;6(4):408-12. [2]. PRMT5 Associates With the FOXP3 Homomer and When Disabled Enhances Targetedp185erbB2/neu Tumor Immunotherapy.Front Immunol. 2019 Feb 8;10:174.
Additional Infomation	See also: DS-437 (annotation moved to).

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~314.50 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.23 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 (5.23 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 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 (5.23 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	2.5160 mL	12.5802 mL	25.1604 mL
	5 mM	0.5032 mL	2.5160 mL	5.0321 mL
	10 mM	0.2516 mL	1.2580 mL	2.5160 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.