| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| 500mg |
|
||
| 1g | |||
| Other Sizes |
| Targets |
iGOT1-01 targets aspartate aminotransferase 1 (GOT1). GOT1 is a key enzyme in the malate-aspartate shuttle that supports cellular redox balance and metabolic flux. iGOT1-01 functions as a GOT1 inhibitor, disrupting the shuttle and affecting cellular metabolism. Inhibition of GOT1 leads to reduced cancer cell viability.
|
|---|---|
| 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).
In vitro, iGOT1-01 shows IC50 values of 85 μM in MDH-coupled GOT1 enzymatic assay and 11.3 μM in the GOT1/GLOX/HRP assay. It demonstrates potent GOT1 inhibition and anticancer activity. Cellular activity of iGOT1-01 has been evaluated in cancer cell lines, showing anticancer effects. |
| 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].
Specific in vivo activity data for iGOT1-01 are not extensively reported. As a GOT1 inhibitor with anticancer activity, it would be expected to show efficacy in animal models of cancer. Further studies would be required to evaluate its therapeutic potential. |
| Enzyme Assay |
GOT1 enzymatic activity is measured using coupled enzyme assays. GOT1 is incubated with aspartate and α-ketoglutarate in the presence of iGOT1-01 at varying concentrations. Product formation (oxaloacetate) is measured by coupling to malate dehydrogenase (MDH) and monitoring NADH oxidation, or using the GOT1/GLOX/HRP assay system. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
The cellular activity of iGOT1-01 is evaluated in cancer cell lines. Cells are treated with the compound, and cell viability is measured using MTT or CellTiter-Glo assays. Metabolic flux and redox balance are assessed to determine the compound's effects on cancer cell metabolism.
|
| 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). In vivo efficacy of iGOT1-01 would typically be evaluated in xenograft mouse models of cancer. Animals would be administered the compound, and tumor growth inhibition would be assessed. Tumor GOT1 activity and metabolite levels would be measured as pharmacodynamic endpoints. |
| ADME/Pharmacokinetics |
iGOT1-01 has a molecular formula of C19H20N4O and a molecular weight of 320.40 g/mol. Its IUPAC name is 4-(1H-Indol-4-yl)-N-phenylpiperazine-1-carboxamide. It is soluble in DMSO (100 mg/mL). Purity is 98%.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicological data for iGOT1-01 are limited. The compound is intended for research use only. Standard laboratory safety precautions should be followed when handling this compound.
|
| 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. |
| Additional Infomation |
iGOT1-01 is a potent GOT1 inhibitor with anticancer activity. It is a valuable tool for studying the role of GOT1 and the malate-aspartate shuttle in cancer metabolism and for developing potential therapeutic strategies.
|
| 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)
|
| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
