DSR-6434 (DSR6434) is a novel and selective Toll-like receptor 7 (TLR7) agonist with antitumor effects. It activated TLR7 with EC50s of 7.2 nM and 4.6 nM for human and mice TLR7, respectively. DSR-6434 exhibited an optimal balance between the agonistic potency and high water solubility. It also demonstrated a strong antitumor effect in vivo by intravenous administration in a tumor bearing mice model.

Physicochemical Properties

Molecular Formula	C19H28N8O2
Molecular Weight	400.487
Exact Mass	400.233
Elemental Analysis	C, 56.98; H, 7.05; N, 27.98; O, 7.99
CAS #	1059070-10-8
PubChem CID	25071151
Appearance	Light yellow to yellow solid powder
Density	1.3±0.1 g/cm3
Index of Refraction	1.635
LogP	0.23
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	10
Heavy Atom Count	29
Complexity	522
Defined Atom Stereocenter Count	0
SMILES	O=C1NC2C(N)=NC(NCCCC)=NC=2N1CC1C=NC(=CC=1)OCCN(C)C
InChi Key	SSZHESNDOMBSRV-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H28N8O2/c1-4-5-8-21-18-24-16(20)15-17(25-18)27(19(28)23-15)12-13-6-7-14(22-11-13)29-10-9-26(2)3/h6-7,11H,4-5,8-10,12H2,1-3H3,(H,23,28)(H3,20,21,24,25)
Chemical Name	6-Amino-2-(butylamino)-9-[[6-[2-(dimethylamino)ethoxy]-3-pyridinyl]methyl]-7,9-dihydro-8H-purin-8-one
Synonyms	DSR6434 DSR 6434 DSR-6434
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	An NF-κB-driven reporter experiment is carried out in HEK293 cells that have been modified to express either hTLR7, TLR8, or TLR9 in order to evaluate the selectivity of DSR-6434 toward TLR7. In this experiment, NF-κB is activated upon successful binding of DSR-6434 to the particular receptor. Only HEK293 cells expressing hTLR7 can be stimulated by DSR-6434 to activate reporter genes; HEK293 cells expressing hTLR8 or hTLR9, which are physically identical, cannot be stimulated[2].
ln Vivo	Compound 20 (0.1–1 mg/kg; intravenous injection; every two weeks; B6C3F1 mice) administered intraperitoneally for four weeks strongly suppresses lung metastasis, with 78% suppression at 0.1 mg/kg dose (no tumor metastasis in the 1 mg/kg group)[1].
Animal Protocol	Animal/Disease Models: B6C3F1 mice injected with HM-1 ovarian cancer cells[1] Doses: 0.1 mg/kg, 1 mg/kg Route of Administration: intravenous (iv) injection; biweekly; for 4 weeks Experimental Results: Suppressed the Lung metastasis Dramatically, 78% inhibition was seen at 0.1 mg/kg dosing (with no tumor metastasis at the 1 mg/kg group).
References	[1]. Synthesis and evaluation of 8-oxoadenine derivatives as potent Toll-like receptor 7 agonists with high water solubility. Bioorg Med Chem Lett. 2013 Feb 1;23(3):669-72. [2]. A novel systemically administered Toll-like receptor 7 agonist potentiates the effect of ionizing radiation in murine solid tumor models. Int J Cancer. 2014 Aug 15;135(4):820-9.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~312.13 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1 mg/mL (2.50 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.50 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 10.0 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	2.4969 mL	12.4847 mL	24.9694 mL
	5 mM	0.4994 mL	2.4969 mL	4.9939 mL
	10 mM	0.2497 mL	1.2485 mL	2.4969 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.