iGOT1-01 is a potent inhibitor of aspartate aminotransferase 1 (glutamate oxaloacetate aminotransferase 1; GOT1) with IC50 of 85 μM in the MDH-coupled GOT1 enzymatic assay and IC50 in the GOT1/GLOX/HRP assay is 11.3 μM. iGOT1-01 has anti-cancer effect.

Physicochemical Properties

Molecular Formula	C19H20N4O
Molecular Weight	320.4
Exact Mass	320.164
Elemental Analysis	C, 71.23; H, 6.29; N, 17.49; O, 4.99
CAS #	882256-55-5
PubChem CID	2818038
Appearance	Solid powder
LogP	3.597
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Heavy Atom Count	24
Complexity	429
Defined Atom Stereocenter Count	0
SMILES	O=C(N1CCN(C2C3=C(NC=C3)C=CC=2)CC1)NC1C=CC=CC=1
InChi Key	MGSDOEMLWKEWSV-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H20N4O/c24-19(21-15-5-2-1-3-6-15)23-13-11-22(12-14-23)18-8-4-7-17-16(18)9-10-20-17/h1-10,20H,11-14H2,(H,21,24)
Chemical Name	4-(1H-Indol-4-yl)-N-phenylpiperazine-1-carboxamide
Synonyms	iGOT101; iGOT1 01; iGOT1-01； iGOT 101; iGOT-101;
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	iGOT1-01's IC50 in the GOT1/MDH1 test was 84.6 μM. iGOT1-01 did not exhibit any inhibitory action on MDH1 by itself at a dose of 100 μM [2]. iGOT1-01 demonstrated minimal harm in two cell viability measurements using PaTu8902 pancreatic cancer cells and DLD1 colon cancer cells (3.125-200 μM; for 3 hours).
ln Vivo	iGOT1-01 (Compound 1a; 20 mg/kg; oral) has reasonable bioavailability and exposure characteristics (t1/2=0.7 hours, Cmax=4133 ng/mL, AUC (0-24 hours)=11734 hours·ng /mL) [1].
Animal Protocol	Animal/Disease Models: 9weeks old female CD1 mice [1] Doses: 20 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Oral Experimental Results: Reasonable bioavailability and exposure characteristics (t1/2=0.7 hrs (hrs (hours)), Cmax=4133 ng/mL, AUC (0-24 hrs (hrs (hours)))=11734 hrs (hrs (hours))·ng/mL).
References	[1]. Justin Anglin, et al. Discovery and optimization of aspartate aminotransferase 1 inhibitors to target redox balance in pancreatic ductal adenocarcinoma. Bioorg Med Chem Lett. 2018 Sep 1;28(16):2675-2678. [2]. Melissa C Holt, et al. Biochemical Characterization and Structure-Based Mutational Analysis Provide Insight into the Binding and Mechanism of Action of Novel Aspartate Aminotransferase Inhibitors. Biochemistry. 2018 Nov 27;57(47):6604-6614.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~312.12 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.80 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 (7.80 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 (7.80 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1211 mL	15.6055 mL	31.2110 mL
	5 mM	0.6242 mL	3.1211 mL	6.2422 mL
	10 mM	0.3121 mL	1.5605 mL	3.1211 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.