JBSNF-000028 TFA

• CAT Number: I041221
• Molecular Formula: C13H14F3N3O2
• Molecular Weight: 301.26
• Purity: ≥95%
• Synonyms: 10-methyl-1,10-diazatricyclo[6.3.1.04,12]dodeca-4(12),5,7-trien-11-imine;2,2,2-trifluoroacetic acid
• InChI: InChI=1S/C11H13N3.C2HF3O2/c1-13-7-9-4-2-3-8-5-6-14(10(8)9)11(13)12;3-2(4,5)1(6)7/h2-4,12H,5-7H2,1H3;(H,6,7)
• InChIKey: WLCIAJGSNKEYTP-UHFFFAOYSA-N
• SMILES: CN1CC2=CC=CC3=C2N(C1=N)CC3.C(=O)(C(F)(F)F)O

JBSNF-000028 TFA is an orally active nicotinamide N-methyltransferase (NNMT) inhibitor with IC50s of 0.033 μM, 0.19 μM and 0.21 μM against human NNMT (hNNMT), monkey NNMT (mkNNMT), and mouse NNMT (mNNMT), respectively. JBSNF-000028 TFA can be used for the research of metabolic disorders[1].
JBSNF-000028 TFA (24 h) inhibits NNMT activity with an EC50 of 2.5 μM in U2OS cells[1].
JBSNF-000028 TFA (10-100 μM; 72 h) has no cytotoxicity against HepG2 cells[1].
JBSNF-000028 TFA binds below a hairpin structural motif at the nicotinamide pocket and stacks between Tyr-204 (from Hairpin) and Leu-164 (from central domain)[1].
JBSNF-000028 TFA is inactive against a broad panel of targets related to metabolism and safety[1].
JBSNF-000028 TFA (50 mg/kg; p.o.; twice daily for 27 days) improves glucose and lipid handling in mice with diet-induced obesity (DIO)[1].
JBSNF-000028 TFA (50 mg/kg; p.o.; twice daily for 4 weeks) improves glucose tolerance in NNMT knockout mice with diet-induced obesity[1].

Reference

[1]. Ruf S, et al. Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders. Sci Rep. 2022 Sep 14;12(1):15440.
 [Content Brief]