Synonym
Jmv 390-1; Jmv-390-1; Jmv390-1;
IUPAC/Chemical Name
((R)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl)-L-isoleucyl-L-leucine
InChi Key
MWZOULASPWUGJJ-NFBUACBFSA-N
InChi Code
InChI=1S/C23H35N3O6/c1-5-15(4)20(22(29)24-18(23(30)31)11-14(2)3)25-21(28)17(13-19(27)26-32)12-16-9-7-6-8-10-16/h6-10,14-15,17-18,20,32H,5,11-13H2,1-4H3,(H,24,29)(H,25,28)(H,26,27)(H,30,31)/t15-,17+,18-,20-/m0/s1
SMILES Code
CC(C)C[C@@H](C(O)=O)NC([C@H]([C@@H](C)CC)NC([C@H](CC1=CC=CC=C1)CC(NO)=O)=O)=O
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
>3 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
2934.99.03.00
Biological target:
JMV 390-1 is a potent multipeptidase inhibitor. JMV 390-1 behaves as a full inhibitor of the major neurotensin (NT)/neuromedin N (NN) degrading enzymes in vitro with IC50 values from 30 to 60 nM.
In vitro activity:
Finally, this study sought to address whether DPP 3 influences the intracellular expression of Ang-(1–7) in the HK-2 cells by chronically treating the cells with JMV-390. Treatment with 20nM and 200 nM JMV reduced activity by 35% (76 ±13 fmol/min/mg, n = 2) and 85% (17±3 fmol/min/mg; p<0.05, n = 3), respectively. In Fig. 6B, basal content of Ang-(1–7) in the HK-2 cells was 22 ±2 fmol/mg protein (n = 3).
Reference: Peptides. 2016 Sep;83:29-37. https://pubmed.ncbi.nlm.nih.gov/27315786/
In vivo activity:
Furthermore, icv injection of compound 6a (JMV 390-1) (10 micrograms/mouse) was found to significantly potentiate the hypothermic effects of NT or NN.
Reference: J Med Chem. 1993 May 14;36(10):1369-79. https://pubmed.ncbi.nlm.nih.gov/8496905/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
449.55
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. Cruz-Diaz N, Wilson BA, Pirro NT, Brosnihan KB, Marshall AC, Chappell MC. Identification of dipeptidyl peptidase 3 as the Angiotensin-(1-7) degrading peptidase in human HK-2 renal epithelial cells. Peptides. 2016 Sep;83:29-37. doi: 10.1016/j.peptides.2016.06.005. Epub 2016 Jun 15. PMID: 27315786; PMCID: PMC5500233.
2. Marshall AC, Pirro NT, Rose JC, Diz DI, Chappell MC. Evidence for an angiotensin-(1-7) neuropeptidase expressed in the brain medulla and CSF of sheep. J Neurochem. 2014 Jul;130(2):313-23. doi: 10.1111/jnc.12720. Epub 2014 Apr 19. PMID: 24661079; PMCID: PMC4137327.
3. Doulut S, Dubuc I, Rodriguez M, Vecchini F, Fulcrand H, Barelli H, Checler F, Bourdel E, Aumelas A, Lallement JC, et al. Synthesis and analgesic effects of N-[3-[(hydroxyamino) carbonyl]-1-oxo-2(R)-benzylpropyl]-L-isoleucyl-L-leucine, a new potent inhibitor of multiple neurotensin/neuromedin N degrading enzymes. J Med Chem. 1993 May 14;36(10):1369-79. doi: 10.1021/jm00062a009. PMID: 8496905.
In vitro protocol:
1. Cruz-Diaz N, Wilson BA, Pirro NT, Brosnihan KB, Marshall AC, Chappell MC. Identification of dipeptidyl peptidase 3 as the Angiotensin-(1-7) degrading peptidase in human HK-2 renal epithelial cells. Peptides. 2016 Sep;83:29-37. doi: 10.1016/j.peptides.2016.06.005. Epub 2016 Jun 15. PMID: 27315786; PMCID: PMC5500233.
2. Marshall AC, Pirro NT, Rose JC, Diz DI, Chappell MC. Evidence for an angiotensin-(1-7) neuropeptidase expressed in the brain medulla and CSF of sheep. J Neurochem. 2014 Jul;130(2):313-23. doi: 10.1111/jnc.12720. Epub 2014 Apr 19. PMID: 24661079; PMCID: PMC4137327.
In vivo protocol:
1. Doulut S, Dubuc I, Rodriguez M, Vecchini F, Fulcrand H, Barelli H, Checler F, Bourdel E, Aumelas A, Lallement JC, et al. Synthesis and analgesic effects of N-[3-[(hydroxyamino) carbonyl]-1-oxo-2(R)-benzylpropyl]-L-isoleucyl-L-leucine, a new potent inhibitor of multiple neurotensin/neuromedin N degrading enzymes. J Med Chem. 1993 May 14;36(10):1369-79. doi: 10.1021/jm00062a009. PMID: 8496905.
1: Kitabgi P, Dubuc I, Nouel D, Costentin J, Cuber JC, Fulcrand H, Doulut S, Rodriguez M, Martinez J. Effects of thiorphan, bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the recovery of neurotensin and neuromedin N released from mouse hypothalamus. Neurosci Lett. 1992 Aug 17;142(2):200-4. PubMed PMID: 1454216.
2: Marshall AC, Pirro NT, Rose JC, Diz DI, Chappell MC. Evidence for an angiotensin-(1-7) neuropeptidase expressed in the brain medulla and CSF of sheep. J Neurochem. 2014 Jul;130(2):313-23. doi: 10.1111/jnc.12720. Epub 2014 Apr 19. PubMed PMID: 24661079; PubMed Central PMCID: PMC4137327.
3: Cruz-Diaz N, Wilson BA, Pirro NT, Brosnihan KB, Marshall AC, Chappell MC. Identification of dipeptidyl peptidase 3 as the Angiotensin-(1-7) degrading peptidase in human HK-2 renal epithelial cells. Peptides. 2016 Sep;83:29-37. doi: 10.1016/j.peptides.2016.06.005. Epub 2016 Jun 15. PubMed PMID: 27315786; PubMed Central PMCID: PMC5500233.
4: Yilmaz EM, Güntert P. NMR structure calculation for all small molecule ligands and non-standard residues from the PDB Chemical Component Dictionary. J Biomol NMR. 2015 Sep;63(1):21-37. doi: 10.1007/s10858-015-9959-y. Epub 2015 Jun 30. PubMed PMID: 26123317.
5: Doulut S, Dubuc I, Rodriguez M, Vecchini F, Fulcrand H, Barelli H, Checler F, Bourdel E, Aumelas A, Lallement JC, et al. Synthesis and analgesic effects of N-[3-[(hydroxyamino) carbonyl]-1-oxo-2(R)-benzylpropyl]-L-isoleucyl-L-leucine, a new potent inhibitor of multiple neurotensin/neuromedin N degrading enzymes. J Med Chem. 1993 May 14;36(10):1369-79. PubMed PMID: 8496905.
