WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 585022
CAS#: 351353-48-5
Description: DPTIP is a potent and selective N-SMase2 inhibitor and brain penetrant.
MedKoo Cat#: 585022
Name: DPTIP
CAS#: 351353-48-5
Chemical Formula: C21H18N2O3S
Exact Mass: 378.1038
Molecular Weight: 378.446
Elemental Analysis: C, 66.65; H, 4.79; N, 7.40; O, 12.68; S, 8.47
Synonym: DPTIP
IUPAC/Chemical Name: 2,6-Dimethoxy-4-[4-phenyl-5-(2-thienyl)-1H-imidazol-2-yl]phenol
InChi Key: JMXVHYPSBANVAQ-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H18N2O3S/c1-25-15-11-14(12-16(26-2)20(15)24)21-22-18(13-7-4-3-5-8-13)19(23-21)17-9-6-10-27-17/h3-12,24H,1-2H3,(H,22,23)
SMILES Code: OC1=C(OC)C=C(C2=NC(C3=CC=CC=C3)=C(C4=CC=CS4)N2)C=C1OC
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: >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: 2934.99.9001
| Biological target: | DPTIP is a potent brain penetrant neutral sphingomyelinase 2 (N-SMase 2) inhibitor (exosome inhibitor), with an IC50 of 30 nM. |
| In vitro activity: | Even more, DPTIP showed potent antiviral activity against both viruses with half-maximal effective concentrations (EC50) of 0.26 µM in Vero cells and 2.81 µM in HeLa cells for WNV. Reference: Int J Mol Sci. 2022 Nov 11;23(22):13935. https://pubmed.ncbi.nlm.nih.gov/36430407/ |
| In vivo activity: | Male mice treated with D-DPTIP had significant and robust reduction of hippocampal nSMase2 activity (dark red vs. dark blue; p = 4.5 × 10−7) (Figure 7B). Similarly, female mice treated with D-DPTIP had significantly reduced nSMase2 activity (light red vs. light blue; p = 0.0013). Reference: Pharmaceutics. 2022 Sep 28;14(10):2066. https://pubmed.ncbi.nlm.nih.gov/36297501/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 143.92 | 380.29 |
The following data is based on the product molecular weight 378.446 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. Álvarez-Fernández H, Mingo-Casas P, Blázquez AB, Caridi F, Saiz JC, Pérez-Pérez MJ, Martín-Acebes MA, Priego EM. Allosteric Inhibition of Neutral Sphingomyelinase 2 (nSMase2) by DPTIP: From Antiflaviviral Activity to Deciphering Its Binding Site through In Silico Studies and Experimental Validation. Int J Mol Sci. 2022 Nov 11;23(22):13935. doi: 10.3390/ijms232213935. PMID: 36430407; PMCID: PMC9697135. 2. Rojas C, Barnaeva E, Thomas AG, Hu X, Southall N, Marugan J, Chaudhuri AD, Yoo SW, Hin N, Stepanek O, Wu Y, Zimmermann SC, Gadiano AG, Tsukamoto T, Rais R, Haughey N, Ferrer M, Slusher BS. DPTIP, a newly identified potent brain penetrant neutral sphingomyelinase 2 inhibitor, regulates astrocyte-peripheral immune communication following brain inflammation. Sci Rep. 2018 Dec 7;8(1):17715. doi: 10.1038/s41598-018-36144-2. PMID: 30531925; PMCID: PMC6286365. 3. Tallon C, Bell BJ, Sharma A, Pal A, Malvankar MM, Thomas AG, Yoo SW, Hollinger KR, Coleman K, Wilkinson EL, Kannan S, Haughey NJ, Kannan RM, Rais R, Slusher BS. Dendrimer-Conjugated nSMase2 Inhibitor Reduces Tau Propagation in Mice. Pharmaceutics. 2022 Sep 28;14(10):2066. doi: 10.3390/pharmaceutics14102066. PMID: 36297501; PMCID: PMC9609094. 4. Pal A, Gori S, Yoo SW, Thomas AG, Wu Y, Friedman J, Tenora L, Bhasin H, Alt J, Haughey N, Slusher BS, Rais R. Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP. J Med Chem. 2022 Aug 25;65(16):11111-11125. doi: 10.1021/acs.jmedchem.2c00562. Epub 2022 Aug 5. PMID: 35930706. |
| In vitro protocol: | 1. Álvarez-Fernández H, Mingo-Casas P, Blázquez AB, Caridi F, Saiz JC, Pérez-Pérez MJ, Martín-Acebes MA, Priego EM. Allosteric Inhibition of Neutral Sphingomyelinase 2 (nSMase2) by DPTIP: From Antiflaviviral Activity to Deciphering Its Binding Site through In Silico Studies and Experimental Validation. Int J Mol Sci. 2022 Nov 11;23(22):13935. doi: 10.3390/ijms232213935. PMID: 36430407; PMCID: PMC9697135. 2. Rojas C, Barnaeva E, Thomas AG, Hu X, Southall N, Marugan J, Chaudhuri AD, Yoo SW, Hin N, Stepanek O, Wu Y, Zimmermann SC, Gadiano AG, Tsukamoto T, Rais R, Haughey N, Ferrer M, Slusher BS. DPTIP, a newly identified potent brain penetrant neutral sphingomyelinase 2 inhibitor, regulates astrocyte-peripheral immune communication following brain inflammation. Sci Rep. 2018 Dec 7;8(1):17715. doi: 10.1038/s41598-018-36144-2. PMID: 30531925; PMCID: PMC6286365. |
| In vivo protocol: | 1. Tallon C, Bell BJ, Sharma A, Pal A, Malvankar MM, Thomas AG, Yoo SW, Hollinger KR, Coleman K, Wilkinson EL, Kannan S, Haughey NJ, Kannan RM, Rais R, Slusher BS. Dendrimer-Conjugated nSMase2 Inhibitor Reduces Tau Propagation in Mice. Pharmaceutics. 2022 Sep 28;14(10):2066. doi: 10.3390/pharmaceutics14102066. PMID: 36297501; PMCID: PMC9609094. 2. Pal A, Gori S, Yoo SW, Thomas AG, Wu Y, Friedman J, Tenora L, Bhasin H, Alt J, Haughey N, Slusher BS, Rais R. Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP. J Med Chem. 2022 Aug 25;65(16):11111-11125. doi: 10.1021/acs.jmedchem.2c00562. Epub 2022 Aug 5. PMID: 35930706. |
Rojas et al (2018) DPTIP, a newly identified potent brain penetrant neutral sphingomyelinase 2 inhibitor, regulates astrocyte-peripheral immune communication following brain inflammation. Sci.Rep. 8 17715 PMID: 30531925
