Delpazolid, formerly known as LCB01-0371, is a new oxazolidinone with cyclic amidrazone. In vitro activity of LCB01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. LCB01-0371 showed good activity against Gram-positive pathogens. In vivo activity of LCB01-0371 against systemic infections in mice was also evaluated. LCB01-0371 was more active than linezolid against these systemic infections. LCB01-0371 showed bacteriostatic activity against Staphylococcus aureus.

Physicochemical Properties

Molecular Formula	C14H17FN4O3
Molecular Weight	308.3134
Exact Mass	308.128
Elemental Analysis	C, 54.54; H, 5.56; F, 6.16; N, 18.17; O, 15.57
CAS #	1219707-39-7
Related CAS #	1219707-39-7;
PubChem CID	44205191
Appearance	Solid powder
Density	1.5±0.1 g/cm3
Boiling Point	481.8±55.0 °C at 760 mmHg
Flash Point	245.2±31.5 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.645
LogP	-1.05
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Heavy Atom Count	22
Complexity	450
Defined Atom Stereocenter Count	1
SMILES	FC1C([H])=C(C([H])=C([H])C=1N1C([H])=NN(C([H])([H])[H])C([H])([H])C1([H])[H])N1C(=O)O[C@@]([H])(C([H])([H])O[H])C1([H])[H]
InChi Key	QLUWQAFDTNAYPN-LLVKDONJSA-N
InChi Code	InChI=1S/C14H17FN4O3/c1-17-4-5-18(9-16-17)13-3-2-10(6-12(13)15)19-7-11(8-20)22-14(19)21/h2-3,6,9,11,20H,4-5,7-8H2,1H3/t11-/m1/s1
Chemical Name	(5R)-3-[3-fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one
Synonyms	Delpazolid; LCB01-0371; LCB 01-0371; LCB-01-0371; LCB010371; LCB 010371; LCB-010371.
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

Targets	Oxazolidinone
ln Vitro	After 24 hours, delapazol (LCB01-0371) demonstrates bacteriostatic activity against MSSA and MRSA at concentrations of 1×MIC and 2×MIC. Delpazolid exhibits bacteriostatic activity at concentrations of 4×MIC and 8×MIC, but after 24 hours of incubation, there is no regrowth at these concentrations[1]. Delpazolid (LCB-0371) (MIC50=1.2 μg/mL) significantly reduces M. abscessus survival. At concentrations of 0.1, 1, and 10 μg/mL, delapazolid significantly reduces the amount of intracellular mycobacteria that are present two days after infection[2].
ln Vivo	Delpazolid (LCB01-0371) exhibits strong protective effects against systemic infections brought on by both Gram-positive and Gram-negative bacteria when taken orally. Delpazolid's ED50 against S. aureus Giorgio (MSSA) infection is 4.53 mg/kg of body weight. Delpazolid's ED50 against S. aureus p125 (MRSA) is 2.96 mg/kg[1]. Seven days after infection, mice's lung colony-forming unit (CFU) counts tend to be lower when Delpazolid (LCB-0371) is given orally at a dose of 100 mg/kg per day (by gavage)[2].
Cell Assay	In order to perform the in vitro infection process, 2×105 cells/well of bone marrow-derived macrophages (BMDMs) are plated and infected with M. abscessus for 4 hours. After giving the cells a PBS wash to get rid of extracellular bacteria, Delpazolid (LCB-0371) is added to the medium and left for two days. Following the extraction of the intracellular bacteria, the lysates are diluted ten times in PBS. Every sample is plated onto 7H10 agar plates and then incubated for seven days at 37°C in an incubator with 0.5% CO2[2].
Animal Protocol	Intranasal or intravenous injections of M. Abscessus (1×107 CFU/mouse) are given to WT mice. Following a 2-day period, the mice receive Delpazolid (LCB-0371) orally for a consecutive 4-day period. The mice are killed seven days after contracting M. Abscessus, and their livers, lungs, and spleens are homogenized in PBS. The homogenates are plated at serial dilutions on 7H10 medium that has been enhanced with 10% OADC (oleic acid, albumin, dextrose, and catalase)[2].
References	[1]. In vitro and in vivo activities of LCB01-0371, a new oxazolidinone. Antimicrob Agents Chemother. 2010 Dec;54(12):5359-62. [2]. Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus. Antimicrob Agents Chemother. 2017 Aug 24;61(9).
Additional Infomation	Delpazolid (LCB01-0371) is under investigation in clinical trial NCT01554995 (A Clinical Study, Randomized, Double-blind, Placebo-controlled, Single Dose Study).

Solubility Data

Solubility (In Vitro)

DMSO :~30 mg/mL (~97.30 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.11 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 (8.11 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 25.0 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: ≥ 2.5 mg/mL (8.11 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. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (8.11 mM)  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.2435 mL	16.2174 mL	32.4349 mL
	5 mM	0.6487 mL	3.2435 mL	6.4870 mL
	10 mM	0.3243 mL	1.6217 mL	3.2435 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.