TLR4-IN-C34 is an orally bioactive TLR4 inhibitor that improves systemic inflammation in models of endotoxemia and necrotizing enterocolitis.

Physicochemical Properties

Molecular Formula	C17H27NO9
Molecular Weight	389.397586107254
Exact Mass	389.168
Elemental Analysis	C, 52.44 H, 6.99 N, 3.60 O, 36.98
CAS #	40592-88-9
PubChem CID	91691128
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	519.8±50.0 °C at 760 mmHg
Flash Point	268.2±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.484
LogP	0.83
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	10
Heavy Atom Count	27
Complexity	563
Defined Atom Stereocenter Count	5
SMILES	O1[C@@H]([C@@H]([C@H]([C@@H]([C@H]1COC(C)=O)OC(C)=O)OC(C)=O)NC(C)=O)OC(C)C
InChi Key	KMIQMFHPUJUDMC-HHARLNAUSA-N
InChi Code	InChI=1S/C17H27NO9/c1-8(2)24-17-14(18-9(3)19)16(26-12(6)22)15(25-11(5)21)13(27-17)7-23-10(4)20/h8,13-17H,7H2,1-6H3,(H,18,19)/t13-,14-,15-,16-,17+/m1/s1
Chemical Name	[(2R,3S,4R,5R,6S)-5-acetamido-3,4-diacetyloxy-6-propan-2-yloxyoxan-2-yl]methyl acetate
Synonyms	TLR4-C34; TLR4-C-34; TLR4-C 34; C34; C 34; C-34; TLR4-IN-C34; Toll-Like Receptor 4-C34;
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 Vivo	TLR4-IN-C34 (C34, orally administered once daily at a dose of 1 mg/kg) has been shown to significantly protect the intestinal mucosa and lessen the severity of NEC [1].
Animal Protocol	Animal/Disease Models: Experimental NEC induction in 7-8 day-old mice [1]. Doses: 1 mg/kg. Doses: Take orally every morning Experimental Results: diminished intestinal inflammation.
References	[1]. Discovery and validation of a new class of small molecule Toll-like receptor 4 (TLR4) inhibitors. PLoS One. 2013 Jun 12;8(6):e65779. [2]. Synthesis of anti-inflammatory α-and β-linked acetamidopyranosides as inhibitors of toll-like receptor 4 (TLR4). Tetrahedron Lett. 2015 Jun 3;56(23):3097-3100.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~642.01 mM) H2O : ~33.33 mg/mL (~85.59 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6.25 mg/mL (16.05 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 62.5 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: ≥ 6.25 mg/mL (16.05 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 62.5 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: ≥ 6.25 mg/mL (16.05 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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 4: 7.69 mg/mL (19.75 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5681 mL	12.8403 mL	25.6805 mL
	5 mM	0.5136 mL	2.5681 mL	5.1361 mL
	10 mM	0.2568 mL	1.2840 mL	2.5681 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.