Synonym
SirReal 2; SirReal-2; SirReal2;
IUPAC/Chemical Name
2-[(4,6-Dimethyl-2-pyrimidinyl)thio]-N-[5-(1-naphthalenylmethyl)-2-thiazolyl]acetamide
InChi Key
MENNDDDTIIZDDN-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H20N4OS2/c1-14-10-15(2)25-22(24-14)28-13-20(27)26-21-23-12-18(29-21)11-17-8-5-7-16-6-3-4-9-19(16)17/h3-10,12H,11,13H2,1-2H3,(H,23,26,27)
SMILES Code
O=C(NC1=NC=C(CC2=C3C=CC=CC3=CC=C2)S1)CSC4=NC(C)=CC(C)=N4
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
>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:
SirReal 2 is a selective SIRT2 inhibitor (IC50 = 140 nM) that has a minimal effect on SIRT1 and SIRT3-6. SirReal 2 increases α-tubulin acetylation levels in HeLa cells.
In vitro activity:
Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity by compounds such as SirReal 2 a promising strategy for pharmaceutical intervention. Application of SirReal2 in HeLa cells led to tubulin hyperacetylation and induced destabilization of the checkpoint protein BubR1, which is consistent with Sirt2 inhibition in vivo.
Reference: Nat Commun. 2015 Feb 12;6:6263. https://pubmed.ncbi.nlm.nih.gov/25672491/
In vivo activity:
Mice were injected with different SIRT1 and SIRT2 inhibitors, one of which being SirReal2. These inhibitors did not demonstrate any change in the infarction volume or the apoptotic index, compared to the control samples. Results indicated that the involvement of these sirtuins in the response of brain cells to ischemia in the first 24 h, but the alterations in their expression and change in the localization of SIRT1 are not related to the regulation of penumbra cell apoptosis in the acute period after PTS..
Reference: Front Physiol. 2022 Apr 27;13:782684. https://pubmed.ncbi.nlm.nih.gov/35574497/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
42.1 |
100.00 |
|
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
420.54
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. Kawaguchi M, Ieda N, Nakagawa H. Development of Peptide-Based Sirtuin Defatty-Acylase Inhibitors Identified by the Fluorescence Probe, SFP3, That Can Efficiently Measure Defatty-Acylase Activity of Sirtuin. J Med Chem. 2019 Jun 13;62(11):5434-5452. doi: 10.1021/acs.jmedchem.9b00315. Epub 2019 May 30. PMID: 31117516.
2. Rumpf T, Schiedel M, Karaman B, Roessler C, North BJ, Lehotzky A, Oláh J, Ladwein KI, Schmidtkunz K, Gajer M, Pannek M, Steegborn C, Sinclair DA, Gerhardt S, Ovádi J, Schutkowski M, Sippl W, Einsle O, Jung M. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. Nat Commun. 2015 Feb 12;6:6263. doi: 10.1038/ncomms7263. PMID: 25672491; PMCID: PMC4339887.
3. Luo Y, Zhao H, Zhu J, Zhang L, Zha J, Zhang L, Ding Y, Jian X, Xia J, Xu B, Qi Z. SIRT2 inhibitor SirReal2 enhances anti-tumor effects of PI3K/mTOR inhibitor VS-5584 on acute myeloid leukemia cells. Cancer Med. 2023 Sep;12(18):18901-18917. doi: 10.1002/cam4.6480. Epub 2023 Sep 1. PMID: 37658623; PMCID: PMC10557894.
4. Eid M, Dzreyan V, Demyanenko S. Sirtuins 1 and 2 in the Acute Period After Photothrombotic Stroke: Expression, Localization and Involvement in Apoptosis. Front Physiol. 2022 Apr 27;13:782684. doi: 10.3389/fphys.2022.782684. PMID: 35574497; PMCID: PMC9092253.
In vitro protocol:
1. Kawaguchi M, Ieda N, Nakagawa H. Development of Peptide-Based Sirtuin Defatty-Acylase Inhibitors Identified by the Fluorescence Probe, SFP3, That Can Efficiently Measure Defatty-Acylase Activity of Sirtuin. J Med Chem. 2019 Jun 13;62(11):5434-5452. doi: 10.1021/acs.jmedchem.9b00315. Epub 2019 May 30. PMID: 31117516.
2. Rumpf T, Schiedel M, Karaman B, Roessler C, North BJ, Lehotzky A, Oláh J, Ladwein KI, Schmidtkunz K, Gajer M, Pannek M, Steegborn C, Sinclair DA, Gerhardt S, Ovádi J, Schutkowski M, Sippl W, Einsle O, Jung M. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. Nat Commun. 2015 Feb 12;6:6263. doi: 10.1038/ncomms7263. PMID: 25672491; PMCID: PMC4339887.
In vivo protocol:
1. Luo Y, Zhao H, Zhu J, Zhang L, Zha J, Zhang L, Ding Y, Jian X, Xia J, Xu B, Qi Z. SIRT2 inhibitor SirReal2 enhances anti-tumor effects of PI3K/mTOR inhibitor VS-5584 on acute myeloid leukemia cells. Cancer Med. 2023 Sep;12(18):18901-18917. doi: 10.1002/cam4.6480. Epub 2023 Sep 1. PMID: 37658623; PMCID: PMC10557894.
2. Eid M, Dzreyan V, Demyanenko S. Sirtuins 1 and 2 in the Acute Period After Photothrombotic Stroke: Expression, Localization and Involvement in Apoptosis. Front Physiol. 2022 Apr 27;13:782684. doi: 10.3389/fphys.2022.782684. PMID: 35574497; PMCID: PMC9092253.
1: Schiedel M, Herp D, Hammelmann S, Swyter S, Lehotzky A, Robaa D, Oláh J, Ovádi J, Sippl W, Jung M. Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals). J Med Chem. 2018 Jan 25;61(2):482-491. doi: 10.1021/acs.jmedchem.6b01872. Epub 2017 Apr 17. PubMed PMID: 28379698.
2: Schiedel M, Rumpf T, Karaman B, Lehotzky A, Gerhardt S, Ovádi J, Sippl W, Einsle O, Jung M. Structure-Based Development of an Affinity Probe for Sirtuin 2. Angew Chem Int Ed Engl. 2016 Feb 5;55(6):2252-6. doi: 10.1002/anie.201509843. Epub 2016 Jan 8. PubMed PMID: 26748890.
3: Schiedel M, Rumpf T, Karaman B, Lehotzky A, Oláh J, Gerhardt S, Ovádi J, Sippl W, Einsle O, Jung M. Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure-Activity Relationship Study. J Med Chem. 2016 Feb 25;59(4):1599-612. doi: 10.1021/acs.jmedchem.5b01517. Epub 2016 Jan 7. PubMed PMID: 26696402.
