DprE1-IN-1 is a potent and orally bioactive DprE1 inhibitor (antagonist) with good hepatocyte stability, low cell toxicity/cytotoxicity and low hERG channel inhibition. DprE1-IN-1 has effective resistance to both drug-sensitive and clinically isolated drug-resistant tuberculosis (TB) strains (MICs<0.1 μg/mL), and has good anti-mycobacterial activity in macrophages, which can reduce 1.29 log10CFU.

Physicochemical Properties

Molecular Formula	C19H21N3O6S2
Molecular Weight	451.516542196274
Exact Mass	451.087
CAS #	920459-41-2
PubChem CID	44918622
Appearance	Typically exists as solid at room temperature
LogP	2.8
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	30
Complexity	740
Defined Atom Stereocenter Count	0
SMILES	C(OCC)(=O)NC(C1C=CSC=1NC(=O)C1=CC=C(S(N2CCCC2)(=O)=O)C=C1)=O
InChi Key	FFUVSZKOCCMGPX-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H21N3O6S2/c1-2-28-19(25)21-17(24)15-9-12-29-18(15)20-16(23)13-5-7-14(8-6-13)30(26,27)22-10-3-4-11-22/h5-9,12H,2-4,10-11H2,1H3,(H,20,23)(H,21,24,25)
Chemical Name	ethyl N-[2-[(4-pyrrolidin-1-ylsulfonylbenzoyl)amino]thiophene-3-carbonyl]carbamate
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	DprE1-IN-1 (Compound 17b) has little cytotoxicity and is very safe against HepG2, J774A.1 macrophages (IC50>60 μg/mL), and Vero (IC50=58.18 μg/mL). Its dosage ranges from 64 to 0.26 μg/mL over a 48-hour period. mL), possesses strong therapeutic qualities as well as potent efficacy [1]. M was decreased by three days of treatment with DprE1-IN-1 at 5 μg/mL and 10 μg/mL. TB by 1.19 and 1.29 log10 CFU in J774A.1 macrophages, respectively [1]. In human and mouse hepatocytes, DprE1-IN-1 (compound 17b) (1 μM; 0-120 min) exhibits remarkable stability (residual rates 42% and 49.7%, respectively; t1/2 24.0 and 29.7 min, respectively)[1].
ln Vivo	DprE1-IN-1 (100 mg/kg; oral gavage; 5 days per week, from day 10 to day 30) lowers lung bacterial load by 0.54 after three weeks of treatment in mice infected with Mycobacterium TB H37Rv log10 CFU. 1].
Cell Assay	Cytotoxicity assay Cell Types: Vero, HepG2 and mouse J774A.1 macrophages [1] Tested Concentrations: 64 to 0.26 μg/mL Incubation Duration: 48 hrs (hours) Experimental Results: Demonstrated high safety against HepG2, J774A.1 macrophages and low cytotoxicity (IC50 >60 μg/mL) and Vero (IC50=58.18 μg/mL) with effective efficacy and good druggability.
Animal Protocol	Animal/Disease Models: Female SPF balb/c (Bagg ALBino) mouse (18-20 g) (Mycobacterium tuberculosis H37Rv infection) [1] Doses: 100 mg/kg Route of Administration: po (oral gavage); from day 10 to day 30, 5 days per week Experimental Results: After three weeks of treatment, lung bacterial load was diminished by 0.54 log10 CFU compared to untreated controls.
References	[1]. Qin R, et al. Identification of thiophene-benzenesulfonamide derivatives for the treatment of multidrug-resistant tuberculosis. Eur J Med Chem. 2022;231:114145.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2147 mL	11.0737 mL	22.1474 mL
	5 mM	0.4429 mL	2.2147 mL	4.4295 mL
	10 mM	0.2215 mL	1.1074 mL	2.2147 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.