DprE1-IN-4 is a potent non-covalent DprE1 inhibitor (antagonist) with IC50 of 0.90 μg/mL. DprE1-IN-4 has strong in vitro activity, and its MICs for inhibiting tuberculosis H37Rv and drug-resistant tuberculosis strains are 0.12 μg/mL and 0.24 μg/mL respectively. DprE1-IN-4 exhibited acceptable pharmacokinetic properties and significant bactericidal activity in a mouse model of acute tuberculosis.

Physicochemical Properties

Molecular Weight	415.46
Exact Mass	415.12
CAS #	2419160-96-4
PubChem CID	162642596
Appearance	Typically exists as solid at room temperature
LogP	3.1
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	630
Defined Atom Stereocenter Count	0
InChi Key	HBXACXQRFJZTFF-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H21N3O5S/c1-28-20(27)22-17(25)15-9-12-29-18(15)21-16(24)13-5-7-14(8-6-13)19(26)23-10-3-2-4-11-23/h5-9,12H,2-4,10-11H2,1H3,(H,21,24)(H,22,25,27)
Chemical Name	methyl N-[2-[[4-(piperidine-1-carbonyl)benzoyl]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

Targets	IC50: 0.9±0.2 μg/mL (DprE1)[1]
ln Vitro	With MIC values of 0.12 μg/mL, 0.24 μg/mL, 0.24 μg/mL, and 0.48 μg/mL, respectively, DprE1-IN-4 exhibits strong activity against M. tuberculosis. This activity is shown against isolated clinical strains H37Rv, 13946a, 14862b, and PBTZ169-resistant strain[1]. When it comes to DprE1-overexpressing strains alone, DprE1-IN-4 (0.76-16 μg/mL) exhibits decreased potency, but not when it comes to DprE2-overexpressing or wild-type strains. For DprE1, the IC50 value is 0.9±0.2 μg/mL[1].
ln Vivo	Following oral and IV administration, DprE1-IN-4 demonstrates satisfactory pharmacokinetic characteristics. Its oral dosage of 50 mg/kg results in a high plasma exposure ((AUC)0-∞=657 ng·h/mL) and a high maximum plasma concentration (Cmax=486 ng/mL). It has oral bioavailability (F=7.9%) and is thought to be important enough to investigate further in?in vivo?efficacy research[1]. DprE1-IN-4 (100 mg/kg; once daily; three weeks) demonstrated potency through oral gavage.in vivo?activity, lowering the lung's bacterial load by 2.02?log10?CFU in contrast to the group that received no treatment[1].
References	[1]. Pengxu Wang, et al. Discovery of Novel Thiophene-arylamide Derivatives as DprE1 Inhibitors with Potent Antimycobacterial Activities. J Med Chem. 2021 May 13;64(9):6241-6261.

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	2.4070 mL	12.0349 mL	24.0697 mL
	5 mM	0.4814 mL	2.4070 mL	4.8139 mL
	10 mM	0.2407 mL	1.2035 mL	2.4070 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.