Synonym
JBSNF-000088; JBSNF 000088; JBSNF000088
IUPAC/Chemical Name
6-Methoxynicotinamide
InChi Key
KXDSMFBEVSJYRF-UHFFFAOYSA-N
InChi Code
InChI=1S/C7H8N2O2/c1-11-6-3-2-5(4-9-6)7(8)10/h2-4H,1H3,(H2,8,10)
SMILES Code
O=C(N)C1=CN=C(OC)C=C1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes.
Biological target:
JBSNF-000088 is a potent Nicotinamide N-methyltransferase (NNMT) inhibitor with IC50s of 1.8 µM, 2.8 µM, and 5.0 µM for human NNMT, monkey NNMT and mouse NNMT, respectively.
In vitro activity:
The concentration-dependent inhibitory effect of JBSNF-000088 on NNMT enzymatic activity was tested using a fluorescence based biochemical assay. JBSNF-000088 inhibited human NNMT (hNNMT), monkey NNMT (mkNNMT), and mouse NNMT (mNNMT) enzymatic activities with IC50 values of 1.8, 2.8, and 5.0 µM, respectively (Fig 1A–C). The activity of JBSNF-000088 against hNNMT was also confirmed by an alternative LCMS/MS detection method with an IC50 of 2.4 µM (Fig. 1D). To investigate the inhibitory effect of JBSNF-000088 on endogenous NNMT activity in cells, U2OS or differentiated 3T3L1 cells were treated with JBSNF-000088 for 24 h, and the levels of MNA were assessed by LC-MS/MS. The calculated IC50 values are 1.6 and 6.3 µM, respectively (Fig. 1E-F). The approximately 4-fold right shift in potency observed with the compound tested in 3T3L1 cells as compared to U2OS cells may reflect the higher potency on the human enzyme compared to the mouse enzyme as U2OS is a human cell line whereas 3T3-L1 cells are of murine origin. Cytotoxicity of JBSNF-000088 was investigated in HepG2 cells. The cells were incubated with JBSNF-000088 at 10, 30 and 100 µM concentrations for 72 h and cytotoxicity was measured using the CellTiter-Glo assay kit. JBSNF-000088 did not show any toxicity at the tested concentrations.
Reference: Sci Rep. 2018 Feb 26;8(1):3660. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826917/
In vivo activity:
JBSNF-000088 was investigated in chronic efficacy studies using diet induced obesity (DIO), ob/ob and db/db mouse models. The compound was tested at 50 mg kg−1, b.i.d, via oral route of administration. Throughout the treatment period, the JBSNF-000088 group showed statistically significant reduction in body weight (%) as compared to the vehicle treated group (Fig. 4A). The cumulative food intake was comparable between the JBSNF-000088 treatment group and the vehicle treated group (Fig. 4A). JBSNF-000088 treatment led to a statistically significant reduction in fed blood glucose on day 21 (p < 0.01) compared to vehicle control (Fig. 4B). Further, the treatment group also showed a trend to a reduction in fed plasma insulin that was statistically significant on day 14 (p < 0.01) compared to the control (Fig. 4B).
Reference: Sci Rep. 2018 Feb 26;8(1):3660. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826917/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
45.0 |
295.76 |
|
| Water |
1.5 |
9.86 |
|
| Ethanol |
3.5 |
23.00 |
|
| DMF |
5.0 |
32.86 |
|
| DMSO:PBS (pH 7.2) (1:5) |
0.2 |
1.05 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
152.15
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Kannt A, Rajagopal S, Kadnur SV, Suresh J, Bhamidipati RK, Swaminathan S, Hallur MS, Kristam R, Elvert R, Czech J, Pfenninger A, Rudolph C, Schreuder H, Chandrasekar DV, Mane VS, Birudukota S, Shaik S, Zope BR, Burri RR, Anand NN, Thakur MK, Singh M, Parveen R, Kandan S, Mullangi R, Yura T, Gosu R, Ruf S, Dhakshinamoorthy S. A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2018 Feb 26;8(1):3660. doi: 10.1038/s41598-018-22081-7. PMID: 29483571; PMCID: PMC5826917.
In vitro protocol:
1. Kannt A, Rajagopal S, Kadnur SV, Suresh J, Bhamidipati RK, Swaminathan S, Hallur MS, Kristam R, Elvert R, Czech J, Pfenninger A, Rudolph C, Schreuder H, Chandrasekar DV, Mane VS, Birudukota S, Shaik S, Zope BR, Burri RR, Anand NN, Thakur MK, Singh M, Parveen R, Kandan S, Mullangi R, Yura T, Gosu R, Ruf S, Dhakshinamoorthy S. A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2018 Feb 26;8(1):3660. doi: 10.1038/s41598-018-22081-7. PMID: 29483571; PMCID: PMC5826917.
In vivo protocol:
1. Kannt A, Rajagopal S, Kadnur SV, Suresh J, Bhamidipati RK, Swaminathan S, Hallur MS, Kristam R, Elvert R, Czech J, Pfenninger A, Rudolph C, Schreuder H, Chandrasekar DV, Mane VS, Birudukota S, Shaik S, Zope BR, Burri RR, Anand NN, Thakur MK, Singh M, Parveen R, Kandan S, Mullangi R, Yura T, Gosu R, Ruf S, Dhakshinamoorthy S. A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2018 Feb 26;8(1):3660. doi: 10.1038/s41598-018-22081-7. PMID: 29483571; PMCID: PMC5826917.
1: Kannt A, Rajagopal S, Kadnur SV, Suresh J, Bhamidipati RK, Swaminathan S, Hallur MS, Kristam R, Elvert R, Czech J, Pfenninger A, Rudolph C, Schreuder H, Chandrasekar DV, Mane VS, Birudukota S, Shaik S, Zope BR, Burri RR, Anand NN, Thakur MK, Singh M, Parveen R, Kandan S, Mullangi R, Yura T, Gosu R, Ruf S, Dhakshinamoorthy S. A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2018 Feb 26;8(1):3660. doi: 10.1038/s41598-018-22081-7. PubMed PMID: 29483571; PubMed Central PMCID: PMC5826917.
2. Li Y, Yang B, Miao H, Liu L, Wang Z, Jiang C, Yang Y, Qiu S, Li X, Geng Y, Zhang Y, Liu Y. Nicotinamide N -methyltransferase promotes M2 macrophage polarization by IL6 and MDSC conversion by GM-CSF in gallbladder carcinoma. Hepatology. 2023 Jan 13. doi: 10.1097/HEP.0000000000000028. Epub ahead of print. PMID: 36633260.
