Mtb ATP synthase-IN-1 (compound 6ab) is a potent inhibitor of Mycobacterium tuberculosis (TB) (Mtb) ATP synthesis, with MIC of Mtb of 0.452 ~ 0.499 μg/mL. Mtb ATP synthase-IN-1 has good metabolic stability, low cell toxicity/cytotoxicity (Vero IC50 > 64 μg/mL), and has certain oral bioavailability (F). Mtb ATP synthase-IN-1 may be utilized in research against Mycobacterium tuberculosis (TB).

Physicochemical Properties

Molecular Formula	C17H13N3O4
Molecular Weight	323.302823781967
Exact Mass	323.09
CAS #	2642394-38-3
PubChem CID	162662421
Appearance	Off-white to light brown solid powder
LogP	1.8
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	24
Complexity	562
Defined Atom Stereocenter Count	0
SMILES	C1(=O)C(NCC2=NC=CC=C2)=C(NC2=CC=C3OCOC3=C2)C1=O
InChi Key	ZEYYGLIHJGBVNS-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H13N3O4/c21-16-14(19-8-11-3-1-2-6-18-11)15(17(16)22)20-10-4-5-12-13(7-10)24-9-23-12/h1-7,19-20H,8-9H2
Chemical Name	3-(1,3-benzodioxol-5-ylamino)-4-(pyridin-2-ylmethylamino)cyclobut-3-ene-1,2-dione
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	Mtb ATP synthase-IN-1 shows acceptable oral bioavailability and good metabolic stability at 50 mg/kg orally and 5 mg/kg intravenously (single dose) [1]. Mtb ATP synthase-IN-1 pharmacokinetic parameters in male CD-1 mice [1]. PO (50 mg/kg) IV (5 mg/kg) Cmax (ng/mL) 1333 1241 Tmax (h) 0.83 T1/2 (h) 0.51 0.33 AUC0-t (ng/mL·h) 2197 1667 AUC0-∞ (ng/mL·h) 2198 1672 MRT0-∞ (ng/mL) 1.36 0.28 CL (mL/min/kg) 51.4 F (%) 13.1
Animal Protocol	Animal/Disease Models: Male CD-1 mouse[1] Doses: 50 and 5 mg/kg Doses: oral 50mg/kg, intravenous (iv) (iv)injection 5mg/kg; single dose (pharmacokinetic/PK/PK analysis) Experimental Results: demonstrated good metabolic stability and acceptable oral bioavailability.
References	[1]. Design, synthesis and biological evaluation of diamino substituted cyclobut-3-ene-1,2-dione derivatives for the treatment of drug-resistant tuberculosis. Eur J Med Chem. 2020;206:112538.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~386.64 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0931 mL	15.4655 mL	30.9310 mL
	5 mM	0.6186 mL	3.0931 mL	6.1862 mL
	10 mM	0.3093 mL	1.5466 mL	3.0931 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.