Synonym
ML336; ML-336; ML 336;
IUPAC/Chemical Name
2-[(E)-(1,4-Dimethylpiperazin-2-ylidene)amino]-5-nitro-N-phenylbenzamide
InChi Key
DCAMTBFFNOHDAW-DYTRJAOYSA-N
InChi Code
InChI=1S/C19H21N5O3/c1-22-10-11-23(2)18(13-22)21-17-9-8-15(24(26)27)12-16(17)19(25)20-14-6-4-3-5-7-14/h3-9,12H,10-11,13H2,1-2H3,(H,20,25)/b21-18+
SMILES Code
O=C(NC1=CC=CC=C1)C2=CC([N+]([O-])=O)=CC=C2/N=C3N(C)CCN(C)C/3
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:
ML336 is quinazolinone-based inhibitor against venezuelan equine encephalitis virus (VEEV), with IC50s of 32, 20, and 42 nM for VEEV TC-83 CPE , VEEV V3526 CPE, VEEV Wild Type CPE.
In vitro activity:
Medicinal chemistry optimization resulted in the development of ML336, a first-in-class probe that inhibited a VEEV-induced cytopathic effect in three strains of the virus (TC-83, V3526, and Trinidad donkey) in the low nanomolar range without showing cytotoxicity (> 50 μM, selectivity index > 1500). Furthermore, ML336 dramatically reduced viral titer (> 7.2 log) below a 1 μM compound concentration and features a favorable in vitro pharmacokinetic profile which includes moderate blood-brain barrier permeability.
Reference: Probe Reports from the NIH Molecular Libraries Program [Internet]. 2012 Dec 17 [updated 2013 Nov 7]. https://pubmed.ncbi.nlm.nih.gov/24479198/
In vivo activity:
In vivo safety studies were conducted in mice, and LC-MSNs were not toxic when dosed at 0.11 g LC-MSNs/kg/day for four days. ML336-loaded LC-MSNs showed significant reduction of brain viral titer in VEEV infected mice compared to PBS controls.
Reference: Sci Rep. 2018 Sep 18;8(1):13990. https://pubmed.ncbi.nlm.nih.gov/30228359/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
20.0 |
54.44 |
|
| DMF:PBS (pH 7.2) (1:4) |
0.2 |
0.54 |
|
| DMSO |
10.0 |
27.22 |
|
| Ethanol |
0.2 |
0.54 |
|
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
367.41
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. Lee J, Parvathareddy J, Yang D, Bansal S, O'Connell K, Golden JE, Jonsson CB. Emergence and Magnitude of ML336 Resistance in Venezuelan Equine Encephalitis Virus Depend on the Microenvironment. J Virol. 2020 Oct 27;94(22):e00317-20. doi: 10.1128/JVI.00317-20. PMID: 32878897; PMCID: PMC7592223.
2. Chung D, Schroeder CE, Sotsky J, Yao T, Roy S, Smith RA, Tower NA, Noah JW, McKellip S, Sosa M, Rasmussen L, White EL, Aubé J, Golden JE. ML336: Development of Quinazolinone-Based Inhibitors Against Venezuelan Equine Encephalitis Virus (VEEV). 2012 Dec 17 [updated 2013 Nov 7]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–. PMID: 24479198.
3. LaBauve AE, Rinker TE, Noureddine A, Serda RE, Howe JY, Sherman MB, Rasley A, Brinker CJ, Sasaki DY, Negrete OA. Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection. Sci Rep. 2018 Sep 18;8(1):13990. doi: 10.1038/s41598-018-32033-w. PMID: 30228359; PMCID: PMC6143628.
In vitro protocol:
1. Lee J, Parvathareddy J, Yang D, Bansal S, O'Connell K, Golden JE, Jonsson CB. Emergence and Magnitude of ML336 Resistance in Venezuelan Equine Encephalitis Virus Depend on the Microenvironment. J Virol. 2020 Oct 27;94(22):e00317-20. doi: 10.1128/JVI.00317-20. PMID: 32878897; PMCID: PMC7592223.
2. Chung D, Schroeder CE, Sotsky J, Yao T, Roy S, Smith RA, Tower NA, Noah JW, McKellip S, Sosa M, Rasmussen L, White EL, Aubé J, Golden JE. ML336: Development of Quinazolinone-Based Inhibitors Against Venezuelan Equine Encephalitis Virus (VEEV). 2012 Dec 17 [updated 2013 Nov 7]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–. PMID: 24479198.
In vivo protocol:
1. LaBauve AE, Rinker TE, Noureddine A, Serda RE, Howe JY, Sherman MB, Rasley A, Brinker CJ, Sasaki DY, Negrete OA. Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection. Sci Rep. 2018 Sep 18;8(1):13990. doi: 10.1038/s41598-018-32033-w. PMID: 30228359; PMCID: PMC6143628.
1: Schroeder CE, Yao T, Sotsky J, Smith RA, Roy S, Chu YK, Guo H, Tower NA, Noah JW, McKellip S, Sosa M, Rasmussen L, Smith LH, White EL, Aubé J, Jonsson CB, Chung D, Golden JE. Development of (E)-2-((1,4-dimethylpiperazin-2-ylidene)amino)-5-nitro-N-phenylbenzamide, ML336: Novel 2-amidinophenylbenzamides as potent inhibitors of venezuelan equine encephalitis virus. J Med Chem. 2014 Oct 23;57(20):8608-21. doi: 10.1021/jm501203v. Epub 2014 Oct 7. PubMed PMID: 25244572; PubMed Central PMCID: PMC4207539.
2: Chung D, Schroeder CE, Sotsky J, Yao T, Roy S, Smith RA, Tower NA, Noah JW, McKellip S, Sosa M, Rasmussen L, White EL, Aubé J, Golden JE. ML336: Development of Quinazolinone-Based Inhibitors Against Venezuelan Equine Encephalitis Virus (VEEV). 2012 Dec 17 [updated 2013 Nov 7]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK179829/ PubMed PMID: 24479198.
3: Lent MD, Petrovic LE, Swanson JA, Olson CM. Maternal mental health and the persistence of food insecurity in poor rural families. J Health Care Poor Underserved. 2009 Aug;20(3):645-61. doi: 10.1353/hpu.0.0182. PubMed PMID: 19648695.
