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SRX3305

Cat No.:V145263 Purity: ≥98%
SRX3305 is a BTK/PI3K/BRD4 inhibitor with IC50 values of 6.5 nM, 15 nM, and 4 nM for BTK, PI3Kα, and PI3Kδ, respectively.
SRX3305
SRX3305 Chemical Structure CAS No.: 2409965-28-0
Product category: BTK
This product is for research use only, not for human use. We do not sell to patients.
Size Price
500mg
1g
Other Sizes
Official Supplier of:
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Product Description
SRX3305 is a BTK/PI3K/BRD4 inhibitor with IC50 values of 6.5 nM, 15 nM, and 4 nM for BTK, PI3Kα, and PI3Kδ, respectively. SRX3305 inhibits the proliferation of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) cells in a dose-dependent manner and promotes their apoptosis. SRX3305 exhibits potent antitumor activity but is harmless to healthy cells. SRX3305 inhibits activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals. SRX3305 inhibits the migration of CLL cells to CXCL-12 and CXCL-13. SRX3305 maintains its antitumor activity in ibrutinib-resistant CLL cells. SRX3305 can be used in research on CLL, diffuse large B-cell lymphoma (DLBCL), and MCL.
Biological Activity I Assay Protocols (From Reference)
ln Vitro
SRX3305 (0.1-100 μM; 72 h) inhibited the proliferation of B-cell non-Hodgkin lymphoma (B-NHL) cell lines with an average IC50 value of 1.38 μM[1]. SRX3305 (0.1-100 μM; 72 h) reduced the proliferation of diffuse large B-cell lymphoma (DLBCL) cells, with an IC50 value of approximately 290 nM in OCI-LY3 cells and approximately 920 nM in SU-DHL-6 cells[1]. SRX3305 (0.5-2 μM; 24-48 h) induced apoptosis in HG-3 and OSU-CLL cells in a dose-dependent manner[1]. SRX3305 (0.5–2 μM; 4 h) inhibited key BCR survival signaling pathways in OSU-CLL, MEC-1, and MEC-2 cell lines [1]. SRX3305 (0.16–5 μM; 48 h) inhibited the survival and proliferation of primary malignant B cells isolated from Eμ-TCL1 (CLL model) and Eμ-Myc/TCL1 mice [1]. SRX3305 (0.5–2 μM; 48 h) disrupted matrix survival support and chemokine-induced migration in CLL cells [1]. SRX3305 (0.5–2 μM; 48 h) overcame tumor microenvironment (TME)-induced survival signaling in MEC-1 cells [1]. SRX3305 (0.1–100 μM; 72 h) was active against ibrutinib-resistant HG-3 cells [1]. SRX3305 (10 nM-100 μM; 48 hours) had an IC50 of 1 nM in Mino cells, 58 nM in JeKo-1 cells, 1.1 μM in Granta cells, 1 μM in JeKo-1 BTK C481S mutant cells, and 47 nM in Mino BTK C481S mutant cells[2]. SRX3305 (0.375-2 μM; 48 hours) showed very low toxicity to healthy donor peripheral blood mononuclear cells (PBMCs) or surrounding healthy stromal cells, and also showed very low toxicity to healthy donor B cells[2]. SRX3305 (0.1-10 μM; 48 hours) had antitumor activity against primary Eμ-Myc tumor samples[2]. SRX3305 (0.01-0.5 μM; 1 hour) blocked the activation of BTK and AKT[2]. SRX3305 (0.01–1 μM; 1 h) showed superior efficacy in mantle cell lymphoma (MCL) and ibrutinib-resistant MCL cells [2]. SRX3305 (1 h) still inhibited the phosphorylation of BTK and AKT in Mino cells after inhibitor washout [2]. SRX3305 (0.5–2 μM; 24 h) inhibited the proliferation of JeKo-1 and Mino cells by inducing S/G2 phase cell cycle arrest and promoting apoptosis [2].
References

[1]. A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia. Int J Mol Sci. 2022 Jun 16;23(12):6712.

[2]. Combinatorial inhibition of BTK, PI3K-AKT and BRD4-MYC as a strategy for treatment of mantle cell lymphoma. Mol Biomed. 2022 Jan 15;3(1):2.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C22H20N2O5S
Molecular Weight
424.47
CAS #
2409965-28-0
Appearance
Typically exists as solids at room temperature
SMILES
O=C1C=C(N2CCOCC2)OC3=C1SC=C3C4=CC5=C(OCCN5C(C=C)=O)C=C4
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

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.3559 mL 11.7794 mL 23.5588 mL
5 mM 0.4712 mL 2.3559 mL 4.7118 mL
10 mM 0.2356 mL 1.1779 mL 2.3559 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

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