JBSNF-000088 | CAS#7150-23-4 | NNMT inhibitor

MedKoo Cat#: 562248 | Name: JBSNF-000088

Description:

WARNING: This product is for research use only, not for human or veterinary use.

JBSNF-000088 is an inhibitor of Nicotinamide N-methyltransferase (NNMT) for the treatment of metabolic disorders. BSNF-000088 inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease. In mice with high fat diet (HFD)-induced obesity, JBSNF-000088 treatment caused a reduction in body weight, improved insulin sensitivity and normalized glucose tolerance to the level of lean control mice. These effects were not seen in NNMT knockout mice on HFD, confirming specificity of JBSNF-000088. The compound also improved glucose handling in ob/ob and db/db mice albeit to a lesser extent and in the absence of weight loss. JBSNF-000088 may act as a slow-turnover substrate analog, driving the observed metabolic benefits.

Chemical Structure

JBSNF-000088

CAS#7150-23-4

Theoretical Analysis

MedKoo Cat#: 562248

Name: JBSNF-000088

CAS#: 7150-23-4

Chemical Formula: C7H8N2O2

Exact Mass: 152.0586

Molecular Weight: 152.15

Elemental Analysis: C, 55.26; H, 5.30; N, 18.41; O, 21.03

Price and Availability

Size	Price	Availability
100mg	USD 150.00	Ready to ship
500mg	USD 250.00	Ready to ship
1g	USD 400.00	Ready to ship
2g	USD 650.00	Ready to ship
5g	USD 1,450.00	Ready to ship

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Related CAS #

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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

Appearance

Solid powder

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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C9R10B25

View CoA: current batch, Lot#A8T05K22

QC Data

View QC data: current batch, Lot#C9R10B25

View QC data: current batch, Lot#A8T05K22

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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
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:

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. 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.