SRT3025 HCL 2070015-26-6_Sirtuin_Epigenetics_Signaling Pathways_Products

SRT3025 is an orally bioactive small molecule activator of the SIRT1 enzyme. SRT3025 inhibits RANKL-induced osteoclast differentiation, fusion and resorptive capacity without affecting osteoclast survival. SRT3025 inhibits RANKL-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs) by activating AMPK and deacetylating RelA/p65 lysine 310, critical for activation of the NF-κB signaling pathway.

Physicochemical Properties

Molecular Formula

C31H31N5O2S2.HCL

Molecular Weight

606.2

Exact Mass

605.168

CAS #

2070015-26-6

Related CAS #

1231952-55-8;2070015-26-6 (HCl);

PubChem CID

118986647

Appearance

Light yellow to yellow solid powder

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

811

Defined Atom Stereocenter Count

InChi Key

LGRBDTOIPNDWMN-UHFFFAOYSA-N

InChi Code

InChI=1S/C31H31N5O2S2.ClH/c1-38-17-9-14-26-27(35-29(39-26)22-10-3-2-4-11-22)28(37)33-24-13-6-5-12-23(24)30-34-25-18-21(19-32-31(25)40-30)20-36-15-7-8-16-36;/h2-6,10-13,18-19H,7-9,14-17,20H2,1H3,(H,33,37);1H

Chemical Name

5-(3-methoxypropyl)-2-phenyl-N-[2-[6-(pyrrolidin-1-ylmethyl)-[1,3]thiazolo[5,4-b]pyridin-2-yl]phenyl]-1,3-thiazole-4-carboxamide;hydrochloride

Synonyms

SRT3025;SRT-3025;SRT 3025;SRT3025 HCl

HS Tariff Code

2934.99.9001

Storage

Powder-20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro

In vitro activity: SRT3025 inhibits RANKL-induced osteoclast differentiation, fusion and resorptive capacity without affecting osteoclast survival. SRT3025 inhibits RANKL-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs) by activating AMPK and deacetylating RelA/p65 lysine 310, critical for activation of the NF-κB signaling pathway. SRT3025 acts faster than oxymetholone to improve hematopoiesis. It does not work by direct activation of Sirt1 in hematopoietic cells. SRT3025 might suppress p21 transcription through the down-regulation of Egr1. SRT3025 is found to activate wild-type Sirt1 protein but failed to activate the E230K mutant, an activation-resistant Sirt1 protein (due to a mutation at position 230).

Kinase Assay:

Cell Assay: Cells (HPDE, Panc-1, SU86.86, Patu8988t cells) are treated with vehicle or different concentrations of SRT3025 for 72 hours and submitted to MTT analysis.

ln Vivo

SRT3025 treatment also inhibits tumor growth in Panc-1 xenografts, even though it is not as effective in inhibiting the viability of Panc-1 cells in culture. SRT3025 is well tolerated in mice and has the potential to be used in several diseases. SRT3025 administration expands HSPCs and boosts blood counts while long term SRT3025 administration does not permanently increase or decrease HSC repopulating potential. SRT3025 reduces plasma cholesterol, inflammation, and atherosclerosis in Apoe−/− mice, and it increases hepatic Ldlr expression and Pcsk9 accumulation.

Animal Protocol

Dissolved in PBS containing 1% Hydroxypropyl)-β-cyclodextrine and 12% propylene glycol; 50-200 mg/kg; p.o. administration.

Female athymic nu/nu mice

References

Clin Cancer Res.2016;22(10):2496-507;PLoS One.2015;10(7):e0134391;Stem Cell Res.2015;15(1):130-40.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (165 mM)

Water:<1 mg/mL

Ethanol: 5 mg/mL (8.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 1.25 mg/mL (2.06 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6496 mL	8.2481 mL	16.4962 mL
	5 mM	0.3299 mL	1.6496 mL	3.2992 mL
	10 mM	0.1650 mL	0.8248 mL	1.6496 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

PeptideDB

SRT3025 HCL 2070015-26-6

CAS No.: 2070015-26-6

Physicochemical Properties

Biological Activity

Solubility Data