| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
The primary target of NHI-2 is Lactate Dehydrogenase A (LDHA). It exhibits significantly lower inhibition of LDHB (IC50 = 55.8 µM). The compound's selectivity for LDHA over LDHB makes it a valuable tool for studying the role of LDHA in cancer metabolism. By inhibiting LDHA, NHI-2 reduces lactate production, affects extracellular acidification rate and ATP production, and suppresses tumor growth.
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| ln Vitro |
In vitro, NHI-2 inhibits LDHA with IC50 values of 14.7 µM (NADH) and 10.5 µM (pyruvate). It has a broad spectrum anti-proliferative activity in cancer cells and reduces lactate production in HeLa cells. NHI-2 inhibits cell growth of pancreatic cancer LPC006 and PANC-1 cells and enhances the antiproliferative effects of gemcitabine. It causes apoptosis in colon cancer HCT116 cells. The compound is cytotoxic to HeLa cells with an IC50 of 33.4 µM.
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| ln Vivo |
In vivo, NHI-2 suppresses tumor growth in murine B78 melanoma tumor models. It affects extracellular acidification rate and ATP production. The compound's anti-glycolytic activity translates to in vivo efficacy in cancer models. Its ability to enhance the effects of gemcitabine suggests potential for combination therapy.
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| Enzyme Assay |
General protocols for LDHA enzyme activity assays use recombinant LDHA enzyme. The enzyme is incubated with pyruvate (substrate) and NADH (cofactor) in 100 mM phosphate buffer pH 7.4 at 37°C. The reaction is monitored by measuring the decrease in NADH absorbance at 340 nm. NHI-2 is added at various concentrations, and the percentage inhibition of enzyme activity is calculated. The IC50 values are determined from dose-response curves. Positive controls (known LDHA inhibitors) and negative controls (vehicle only) are included.
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| Cell Assay |
General protocols for anti-proliferative activity assays use cancer cell lines (e.g., HeLa, PANC-1, LPC006, HCT116). Cells are seeded in 96-well plates at 5,000-10,000 cells per well and allowed to adhere overnight. NHI-2 is dissolved in DMSO and diluted in culture medium to various concentrations (1-100 µM). Cells are treated for 24-72 hours. Cell viability is assessed by MTT, CCK-8, or SRB assays. The IC50 values are calculated from dose-response curves. Apoptosis is evaluated by caspase-3/7 activity or Annexin V/PI staining. Lactate production is measured using a colorimetric or fluorometric assay. Extracellular acidification rate and ATP production are measured using Seahorse XF analyzers.
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| Animal Protocol |
General protocols for in vivo efficacy studies use murine tumor xenograft models. Immunodeficient mice are inoculated subcutaneously with cancer cells (e.g., B78 melanoma, PANC-1, HCT116). When tumors reach a certain size, mice are treated with NHI-2 administered orally or intraperitoneally at doses of 10-100 mg/kg daily for 2-4 weeks. Tumor volume is measured every 2-3 days using calipers. Body weight is monitored. At the end of the study, tumors are collected for histopathological examination and biochemical analysis (lactate levels, ATP levels, apoptosis markers). The percentage of tumor growth inhibition is calculated compared to vehicle-treated controls. NHI-2 suppresses tumor growth in murine B78 melanoma models.
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| ADME/Pharmacokinetics |
NHI-2 has a molecular weight of 335.28 g/mol (C17H12F3NO3). It is a selective LDHA inhibitor. Its pharmacokinetic properties, including absorption, distribution, metabolism, and excretion, have not been extensively characterized. In preclinical studies, it is typically administered orally or intraperitoneally. The compound's half-life and bioavailability have not been reported.
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| Toxicity/Toxicokinetics |
The toxicity profile of NHI-2 has not been fully characterized. As an LDHA inhibitor, it may affect normal cells that rely on glycolysis for energy production. Preclinical studies have evaluated its safety in animal models, but comprehensive toxicological data are limited. The compound should be handled with appropriate safety precautions in the laboratory. Further toxicological studies are needed for clinical development.
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| References |
Czyż DM, Willett JW, Crosson S. Brucella abortus Induces a Warburg Shift in Host Metabolism That Is Linked to Enhanced Intracellular Survival of the Pathogen. J Bacteriol. 2017 Jul 11;199(15). pii: e00227-17. doi: 10.1128/JB.00227-17. Print 2017 Aug 1. PubMed PMID: 28559292; PubMed Central PMCID: PMC5512224.
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| Additional Infomation |
Inhibits lactate dehydrogenase A; structure is shown in the first source.
NHI-2 (CAS 1269802-97-2) is a selective inhibitor of Lactate Dehydrogenase A (LDHA). It has anti-glycolytic activity against a variety of cancer cells and suppresses tumor growth in murine models. The compound enhances the antiproliferative effects of gemcitabine and causes apoptosis in cancer cells. It has not received regulatory approval for clinical use. NHI-2 is used primarily as a research tool for studying cancer metabolism, glycolysis, and the role of LDHA in tumorigenesis. No clinical trials have been registered for this compound as a therapeutic agent. |
| Molecular Formula |
C17H12F3NO3
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|---|---|
| Molecular Weight |
335.27729511261
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| Exact Mass |
335.076
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| CAS # |
1269802-97-2
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| PubChem CID |
51355147
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
495.7±55.0 °C at 760 mmHg
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| Flash Point |
253.6±31.5 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.567
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| LogP |
5.14
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
465
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC(=O)C1=CC2=C(C=C(C=C2N1O)C3=CC=CC=C3)C(F)(F)F
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| InChi Key |
YPPFWRWCZNXINO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H12F3NO3/c1-24-16(22)15-9-12-13(17(18,19)20)7-11(8-14(12)21(15)23)10-5-3-2-4-6-10/h2-9,23H,1H3
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| Chemical Name |
Methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylate
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| Synonyms |
NHI-2 NHI 2 NHI2
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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 : ~25 mg/mL (~74.56 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9826 mL | 14.9129 mL | 29.8258 mL | |
| 5 mM | 0.5965 mL | 2.9826 mL | 5.9652 mL | |
| 10 mM | 0.2983 mL | 1.4913 mL | 2.9826 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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