Synonym
VP3.15 Dihydrobromide; VP3.15 2HBr; VP3.15 HBr; VP3.15; VP-3.15; VP 3.15; VP315; VP-315; VP 315;
IUPAC/Chemical Name
(2,3-Diphenyl-2H-[1,2,4]thiadiazol-5-ylidene)-(2-morpholin-4-yl-ethyl)-amine Dihydrobromide
InChi Key
CAJZOXQDSKOPBU-SERMZQFOSA-N
InChi Code
InChI=1S/C20H22N4OS.2BrH/c1-3-7-17(8-4-1)19-22-20(21-11-12-23-13-15-25-16-14-23)26-24(19)18-9-5-2-6-10-18;;/h1-10H,11-16H2;2*1H/b21-20+;;
SMILES Code
[H]Br.[H]Br.N1(CC/N=C2N=C(C3=CC=CC=C3)N(C4=CC=CC=C4)S\2)CCOCC1
Purity
>96% (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
Biological target:
VP3.15 dihydrobromide is a potent, orally bioavailable and CNS-penetrant dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, with IC50s of 1.59 μM and 0.88 μM for PDE7 and GSK-3, respectively.
In vivo activity:
Benefits of the repeated treatment with VP3.15 (see Methods) in EAE mice were evident since the beginning, with the clinical score (CS) decaying faster and to a significantly lower value in the VP3.15-treated EAE mice by day 19 after onset (Figure 1b). For a more quantitative estimation of the healing effect of VP3.15, this study fitted the results to an exponential expression, and the score fraction (Sf) obtained was significantly better (0.2) than the EAE-vehicle group (0.3), thus the treatment with VP3.15 ameliorated EAE effects by 33% compared to the vehicle-treated mice (Figure 1c) by the end of the experiment. In addition to that, the estimated recovery rate (υ) was higher in the treated animals (EAE-Veh = 0.187 days−1; EAE-VP3.15 = 0.226 days−1) and was reflected in the fact that EAE-VP3.15 reached the endpoint Sf of EAE-VEH nearly 10 days before.
Reference: Int J Mol Sci. 2021 Feb 28;22(5):2440. https://pubmed.ncbi.nlm.nih.gov/33671012/
|
Solvent |
mg/mL |
mM |
| Solubility |
| dmso |
62.5 |
118.30 |
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
528.30
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. Benítez-Fernández R, Melero-Jerez C, Gil C, de la Rosa EJ, Martínez A, de Castro F. Dynamics of Central Remyelination and Treatment Evolution in a Model of Multiple Sclerosis with Optic Coherence Tomography. Int J Mol Sci. 2021 Feb 28;22(5):2440. doi: 10.3390/ijms22052440. PMID: 33671012; PMCID: PMC7957639.
2. Sánchez-Cruz A, Villarejo-Zori B, Marchena M, Zaldivar-Díez J, Palomo V, Gil C, Lizasoain I, de la Villa P, Martínez A, de la Rosa EJ, Hernández-Sánchez C. Modulation of GSK-3 provides cellular and functional neuroprotection in the rd10 mouse model of retinitis pigmentosa. Mol Neurodegener. 2018 Apr 16;13(1):19. doi: 10.1186/s13024-018-0251-y. PMID: 29661219; PMCID: PMC5902946.
In vivo protocol:
1. Benítez-Fernández R, Melero-Jerez C, Gil C, de la Rosa EJ, Martínez A, de Castro F. Dynamics of Central Remyelination and Treatment Evolution in a Model of Multiple Sclerosis with Optic Coherence Tomography. Int J Mol Sci. 2021 Feb 28;22(5):2440. doi: 10.3390/ijms22052440. PMID: 33671012; PMCID: PMC7957639.
2. Sánchez-Cruz A, Villarejo-Zori B, Marchena M, Zaldivar-Díez J, Palomo V, Gil C, Lizasoain I, de la Villa P, Martínez A, de la Rosa EJ, Hernández-Sánchez C. Modulation of GSK-3 provides cellular and functional neuroprotection in the rd10 mouse model of retinitis pigmentosa. Mol Neurodegener. 2018 Apr 16;13(1):19. doi: 10.1186/s13024-018-0251-y. PMID: 29661219; PMCID: PMC5902946.
1: Medina-Rodríguez EM, Bribián A, Boyd A, Palomo V, Pastor J, Lagares A, Gil C, Martínez A, Williams A, de Castro F. Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis. Sci Rep. 2017 Mar 3;7:43545. doi: 10.1038/srep43545. PubMed PMID: 28256546; PubMed Central PMCID: PMC5335257.
2: Martín-Álvarez R, Paúl-Fernández N, Palomo V, Gil C, Martínez A, Mengod G. A preliminary investigation of phoshodiesterase 7 inhibitor VP3.15 as therapeutic agent for the treatment of experimental autoimmune encephalomyelitis mice. J Chem Neuroanat. 2017 Mar;80:27-36. doi: 10.1016/j.jchemneu.2016.12.001. Epub 2016 Dec 19. PubMed PMID: 28007551.
Morano, L., Vezzio-Vié, N., Aissanou, A., Egger, T., Aze, A., Fiachetti, S., ... & Basbous, J. (2024). TopBP1 biomolecular condensates: a new therapeutic target in advanced-stage colorectal cancer. bioRxiv, 2024-09.
