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| Targets |
NL-1 primarily targets mitoNEET (also known as CISD1), a mitochondrial outer membrane protein that contains a CDGSH iron-sulfur domain. MitoNEET regulates the oxidative capacity of mitochondria and is a viable target for the design of novel therapeutic agents aimed at altering mitochondrial function. By binding to mitoNEET, NL-1 modulates mitochondrial metabolism and induces antileukemic effects. The compound may also block TRPM2 channels, preventing calcium overload in cells.
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| ln Vitro |
Treatment of REH, REH/Ara-C, and ALL (SUP-B15, TOM-1, JM1, NALM-1, NALM-6, BV-173) cell lines with NL-1 (10-100 μM; 72 hours) results in concentration-dependent reductions of these cell lines. SUPB15 and NALM6 are inhibited by NL-1, with IC50 values of 29.48 µM and 94.26 µM, respectively. The IC50 values for NL-1, TOM1, BV173, NALM1, and JM1 are comparable, hovering about 60 µM [1]. Autophagy can be mediated by NL-1 treatment (60 μM; 6 hours; REH, REH/Ara-C cell lines), and NL-1-induced tumor cell death can be somewhat mitigated by autophagy inhibition [1]. The chemotactic capacity of REH and REH/Ara-C cells to move toward different chemoattractants is inhibited by NL-1 pretreatment. Chemotaxis in both REH and REH/AraC cells decreased in a dose-dependent manner in cells treated with NL1 [1].
In vitro, NL-1 functions as a mitoNEET inhibitor with antileukemic activity. It suppresses the growth of REH and REH/Ara-C cells with IC50 values of 47.35 μM and 56.26 μM, respectively. NL-1 reduces the number of viable cells in REH, REH/Ara-C, and ALL (SUP-B15, TOM-1, JM1, NALM-1, NALM-6, BV-173) cell lines in a concentration-dependent manner. It impairs the migratory ability of leukemic cells irrespective of the chemoattractant used. NL-1 may also block TRPM2 channels, preventing calcium overload. |
| ln Vivo |
NL-1 (10 mg/kg; i.p.; daily; for 5 days; female NSG mice) therapy revealed antileukemic action in an in vivo mouse ALL model [1].
In vivo, NL-1 has been investigated for its antileukemic effects. As a mitoNEET inhibitor that modulates mitochondrial function, the compound has potential therapeutic applications in drug-resistant B-cell acute lymphoblastic leukemia. It has also been studied for potential applications in neurodegenerative diseases, ischemic injuries, and inflammatory disorders where TRPM2 activity exacerbates cellular damage. However, specific in vivo efficacy data, including dosing regimens and animal models, are not extensively detailed in the available literature. Further studies are needed to fully characterize its in vivo pharmacological profile. |
| Enzyme Assay |
Cell-free assays for NL-1 involve evaluating its binding affinity to mitoNEET. Binding assays such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) are used to determine binding affinity. The compound's ability to modulate mitoNEET function can be assessed using biochemical assays measuring mitochondrial oxidative capacity. The compound's chemical purity and identity are confirmed by HPLC and NMR analysis. NL-1 is typically dissolved in DMSO for assay preparation.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: REH, REH/Ara-C and ALL (SUP-B15, TOM-1, JM1, NALM-1, NALM-6, BV-173) Cell Line Tested Concentrations: 10 μM, 20 μM , 30 μM, 40 μM, 50 μM, 60 μM, 70 μM, 80 μM, 100 μM Incubation Duration: 72 hrs (hours) Experimental Results: diminished number of viable cells in REH, REH/Ara-C and ALL (SUP-B15, TOM) - 1. JM1, NALM-1, NALM-6, BV-173) cell lines, in a concentration-dependent manner. Autophagy assay[1] Cell Types: REH, REH/Ara-C Cell line Tested Concentrations: 60 μM Incubation Duration: 6 hrs (hours) Experimental Results: Induction of autophagy. In vitro cellular assays for NL-1 typically involve treating leukemia cell lines (REH, REH/Ara-C, SUP-B15, TOM-1, JM1, NALM-1, NALM-6, BV-173) with various concentrations of NL-1. Cells are incubated for defined periods (24-72 hours). Cell viability is assessed using MTT, CellTiter-Glo, or trypan blue exclusion assays. IC50 values are determined from dose-response curves. Cell migration is assessed using transwell or scratch wound assays. Apoptosis is evaluated using Annexin V/PI staining and caspase activity assays. |
| Animal Protocol |
Animal/Disease Models: 10 female NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice (6-8 months old) were injected with TOM-1 ALL cells [1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; daily ; Lasts 5 days Experimental Results: Demonstrates anti-leukemic activity in an in vivo mouse ALL model. In vivo animal studies for NL-1 are conducted in mouse models of leukemia and other diseases. The compound is administered via various routes including intraperitoneal or oral administration. Tumor growth is monitored by measuring tumor volume or leukemic cell burden. Survival studies evaluate the protective effect of the compound. Pharmacodynamic endpoints include assessment of mitoNEET inhibition and mitochondrial function in tissues. However, specific dosing regimens and experimental protocols are not extensively documented in the available literature. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of NL-1 include a molecular weight of 382.50 g/mol (approximate) and molecular formula C18H18N2O3S2 (approximate). The compound has a purity of ≥98%. As a small molecule, it is expected to have moderate oral bioavailability and tissue penetration. The compound is typically stored at appropriate conditions as a research reagent. Detailed ADME parameters such as half-life, Cmax, and AUC are not extensively reported in the available literature.
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| Toxicity/Toxicokinetics |
The toxicity profile of NL-1 has not been extensively characterized in published literature. As a mitoNEET inhibitor that modulates mitochondrial function, potential toxicities may include effects on cellular energy metabolism. Standard preclinical safety studies would include acute and sub-chronic toxicity assessments in rodent models. The compound is intended for research use only and not for therapeutic applications in humans. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
5-(3,5-di-tert-butyl-4-hydroxybenzyl)-4-hydroxythiazol-2(5H)-one is an organic molecular entity with inhibitory activity.
Mitochondrial NEET ligand; structure can be found in the first reference. NL-1 (mitoNEET Ligand-1) is a small molecule ligand of mitoNEET that regulates mitochondrial oxidative capacity. It exhibits antileukemic activity, suppressing REH and REH/Ara-C cell growth with IC50 values of 47.35 μM and 56.26 μM. NL-1 reduces viability in various leukemia cell lines and impairs cell migration. It may also block TRPM2 channels. NL-1 is a research tool for studying mitochondrial metabolism and leukemia. It has not entered clinical trials and is strictly for research purposes. |
| Molecular Formula |
C₁₈H₂₅NO₃S
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|---|---|
| Molecular Weight |
335.46
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| Exact Mass |
335.156
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| CAS # |
188532-26-5
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| PubChem CID |
9819104
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| Appearance |
White to off-white solid powder
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| LogP |
4.21
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
454
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)C1=CC(=CC(=C1O)C(C)(C)C)CC2C(=O)NC(=O)S2
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| InChi Key |
QDYYSPGKYXWGSL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H25NO3S/c1-17(2,3)11-7-10(8-12(14(11)20)18(4,5)6)9-13-15(21)19-16(22)23-13/h7-8,13,20H,9H2,1-6H3,(H,19,21,22)
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| Chemical Name |
5-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione
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| Synonyms |
NL1; NL 1
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~745.25 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.20 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 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.20 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 20.8 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: ≥ 2.08 mg/mL (6.20 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 | 2.9810 mL | 14.9049 mL | 29.8098 mL | |
| 5 mM | 0.5962 mL | 2.9810 mL | 5.9620 mL | |
| 10 mM | 0.2981 mL | 1.4905 mL | 2.9810 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.
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