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NDMC101

Alias: NDMC101; NDMC 101; NDMC-101; HS Cm; HSCm; HS-Cm
Cat No.:V26329 Purity: ≥98%
NDMC101 is a potent osteoclastogenesis inhibitor that can suppress osteoclast differentiation by downregulating NFATc1 regulatory gene expression.
NDMC101
NDMC101 Chemical Structure CAS No.: 1308631-40-4
Product category: NF-κB
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
NDMC101 is a potent osteoclastogenesis inhibitor that can suppress osteoclast differentiation by downregulating NFATc1 regulatory gene expression. NDMC101 is a similar DPP4 substrate and is an important inhibitor of early T cell activation through inhibition of DPP4. NDMC101 may be utilized in study/research of bone diseases, like rheumatoid arthritis, synovitis, etc.
NDMC101 (CAS#: 1308631-40-4), chemically N-(4-chloro-2-fluorophenyl)-2-hydroxybenzamide, is a salicylanilide derivative that functions as a dual inhibitor of osteoclastogenesis. It is a potent osteoclastogenesis inhibitor that inhibits osteoclast differentiation via down-regulation of NFATc1-modulated gene expression. NDMC101 also acts as an inhibitor of dipeptidyl peptidase-IV (DPP4) activity in human T cells and exhibits immunomodulatory effects. It is used for bone disorder research.
Biological Activity I Assay Protocols (From Reference)
Targets
NF-κB; p38; ERK
NDMC101 targets NF-κB and NFATc1 transcription factors, as well as DPP4 (dipeptidyl peptidase-IV). It inhibits osteoclast differentiation by down-regulating NFATc1-modulated gene expression. It also inhibits DPP4 activity, which is involved in early T-cell activation. The compound inhibits multiple protein kinases including p38, ERK, and JNK. By targeting these pathways, NDMC101 inhibits RANKL-induced osteoclastogenesis.
ln Vitro
NDMC101 (10–15 µM) prevents bone marrow-derived macrophages (BMDMs) and RAW 264.7 cells from differentiating into osteoclasts when RANKL is present[1].
In BMDMs, NDMC101 (15 µM) reduces the osteoclastogenic genes Nfatc1, Acp5, Ctsk, Oscar, Itgb3, and Dcstamp's expression in response to RANKL[1].
In vitro, NDMC101 inhibits RANKL-induced formation of TRAP+ multinucleated cells in RAW264.7 macrophages and bone marrow macrophages (BMMs). It down-regulates NFATc1-modulated gene expression. The compound inhibits DPP4 activity in human T cells. It also inhibits NF-κB and NFATc1 activity. NDMC101 shows immunomodulatory effects and inhibits multiple protein kinases. Detailed in vitro data are available in the primary literature.
ln Vivo
In vivo, NDMC101 inhibits osteoclastogenesis and ameliorates paw swelling and inflammatory bone destruction. It is effective in bone disorder research. The compound shows in vivo efficacy in models of rheumatoid arthritis, synovitis, and other bone diseases. NDMC101 markedly inhibits RANKL-induced osteoclast formation in vivo. Further studies are needed to fully characterize its in vivo efficacy and pharmacokinetic profile.
Enzyme Assay
In vitro osteoclastogenesis assays for NDMC101 typically use RAW264.7 macrophages or bone marrow macrophages (BMMs) stimulated with RANKL and M-CSF. The compound is dissolved in DMSO and diluted in culture medium. Cells are seeded in 96-well plates and treated with NDMC101 at various concentrations (0.1-100 μM) for 5-7 days. Osteoclast formation is assessed by TRAP staining. TRAP+ multinucleated cells (≥3 nuclei) are counted. NFATc1 and NF-κB activity is assessed by Western blotting or reporter assays. DPP4 activity is measured using fluorogenic substrate. Controls include vehicle and known inhibitors.
Cell Assay
For cell-based assays, RAW264.7 macrophages or human T cells are cultured in DMEM or RPMI-1640 with 10% FBS. Cells are seeded in multi-well plates and treated with NDMC101 at various concentrations for 24-72 hours. RANKL is added to induce osteoclast differentiation. TRAP activity is measured by colorimetric assay. Gene expression of osteoclast markers (NFATc1, c-Fos, TRAP, Cathepsin K) is analyzed by RT-PCR. Cytokine production is measured by ELISA. All treatments include vehicle controls and are performed in triplicate.
Animal Protocol
In vivo, NDMC101 is typically administered orally to rodents. The compound is formulated in a suitable vehicle such as 0.5% methylcellulose or PEG-based solutions. For arthritis models (e.g., collagen-induced arthritis or adjuvant-induced arthritis), mice or rats are dosed at various regimens (e.g., 10-50 mg/kg). Endpoints include paw swelling measurement, clinical scoring, histological assessment of bone destruction, and micro-CT analysis of bone architecture. Blood and tissue samples are collected for pharmacokinetic and pharmacodynamic analysis. All procedures follow institutional animal care guidelines.
ADME/Pharmacokinetics
NDMC101 (MW 265.67, C₁₃H₉ClFNO₂) is a salicylanilide derivative. The compound is soluble in DMSO. It shows a purity of ≥98%. Detailed pharmacokinetic parameters are not extensively reported in publicly available sources. The compound is typically stored at -20°C. Further ADME studies are needed to fully characterize its pharmacokinetic profile. The compound is designed for research applications in bone disorders.
Toxicity/Toxicokinetics
Toxicology data for NDMC101 are limited in publicly available sources. As a multi-target inhibitor, potential off-target effects should be considered. The compound is for research use only and not intended for human therapeutic applications. Standard safety pharmacology and toxicology studies would be required for therapeutic development. The compound should be handled with standard laboratory safety precautions.
References

[1]. A benzamide-linked small molecule NDMC101 inhibits NFATc1 and NF-κB activity: a potential osteoclastogenesis inhibitor for experimental arthritis. J Clin Immunol. 2012 Aug;32(4):762-77.

[2]. A salicylate-based small molecule HS-Cm exhibits immunomodulatory effects and inhibits dipeptidyl peptidase-IV activity in human T cells. Eur J Pharmacol. 2014 Mar 5;726:124-32.

Additional Infomation
NDMC101 is a research-grade inhibitor of osteoclastogenesis and DPP4 for studying bone disorders. Its primary applications include bone biology, immunology, and drug discovery. The compound is not approved for clinical use and has not entered clinical trials. It is commercially available from various chemical suppliers for research purposes only. Its mechanism involves inhibition of NFATc1 and NF-κB, DPP4 inhibition, and modulation of inflammatory signaling pathways.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C13H9CLFNO2
Molecular Weight
265.66
Exact Mass
265.03
Elemental Analysis
C, 58.77; H, 3.41; Cl, 13.34; F, 7.15; N, 5.27; O, 12.04
CAS #
1308631-40-4
Related CAS #
1308631-40-4
PubChem CID
60202556
Appearance
White to off-white solid powder
Density
1.5±0.1 g/cm3
Boiling Point
311.1±42.0 °C at 760 mmHg
Flash Point
142.0±27.9 °C
Vapour Pressure
0.0±0.7 mmHg at 25°C
Index of Refraction
1.661
LogP
3.58
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
2
Heavy Atom Count
18
Complexity
303
Defined Atom Stereocenter Count
0
SMILES
C1(C(NC2C=CC(Cl)=CC=2F)=O)=C(C=CC=C1)O
InChi Key
NUQWCDAXACRITO-UHFFFAOYSA-N
InChi Code
InChI=1S/C13H9ClFNO2/c14-8-5-6-11(10(15)7-8)16-13(18)9-3-1-2-4-12(9)17/h1-7,17H,(H,16,18)
Chemical Name
N-(4-chloro-2-fluorophenyl)-2-hydroxybenzamide
Synonyms
NDMC101; NDMC 101; NDMC-101; HS Cm; HSCm; HS-Cm
HS Tariff Code
2934.99.03.00
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 53~100 mg/mL(199.5~376.4 mM)
Ethanol: ~13 mg/mL(~48.9 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.41 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 (9.41 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 3.7642 mL 18.8210 mL 37.6421 mL
5 mM 0.7528 mL 3.7642 mL 7.5284 mL
10 mM 0.3764 mL 1.8821 mL 3.7642 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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03375034 Completed Drug: NDMC 20mg
Drug: NDMC60mg
Neuropathic Pain Jules Desmeules March 30, 2017 Phase 1
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