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AC-4-130

Alias: AC4130 AC-4130 AC4-130 AC-4-130
Cat No.:V6728 Purity: ≥98%
AC-4-130 is a potent STAT5 SH2 domain inhibitor.
AC-4-130
AC-4-130 Chemical Structure CAS No.: 1834571-82-2
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
5mg
10mg
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description
AC-4-130 is a potent STAT5 SH2 domain inhibitor. AC-4-130 directly binds to STAT5 and disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription. AC-4-130 induces cell cycle arrest and apoptosis in FLT3-ITD driven leukemia cells. AC-4-130 has anti-cancer activity and can effectively block pathological levels of STAT5 activity in acute myeloid leukemia (AML).
Biological Activity I Assay Protocols (From Reference)
ln Vitro
Significant increases in MV4-11 or MOLM-13 cells are caused by AC-4-130 (0.1-100 μM; 72 hours) in a formulation- and time-dependent manner [1]. Cell induction cycle is triggered by AC-4-130 (2, 5 μM; 72 hours), which causes a decrease in S or G2/M phase cells and an increase in G0/G1-induced cells [1]. The cytoplasm and nucleus of AC-4-130 (0.5-2; 24 hours) cells displayed decreased pY-STAT5 levels. Primary human AML cells' ability to proliferate and develop clonally was significantly suppressed by AC-4-130-mediated suppression of STAT5, whereas healthy CD34+ cells are less susceptible [1].
References

[1]. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia. 2018 May;32(5):1135-1146.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C37H36CLF5N2O5S
Molecular Weight
751.202165603638
Exact Mass
750.195
CAS #
1834571-82-2
Related CAS #
1834571-82-2;
PubChem CID
154701370
Appearance
Off-white to brown solid powder
LogP
9.1
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
11
Rotatable Bond Count
12
Heavy Atom Count
51
Complexity
1260
Defined Atom Stereocenter Count
0
InChi Key
NMQUSJQZQWKQBL-UHFFFAOYSA-N
InChi Code
InChI=1S/C37H36ClF5N2O5S/c1-36(2,3)24-15-22(16-25(17-24)37(4,5)6)19-45(27-13-9-23(10-14-27)35(47)48)28(46)20-44(18-21-7-11-26(38)12-8-21)51(49,50)34-32(42)30(40)29(39)31(41)33(34)43/h7-17H,18-20H2,1-6H3,(H,47,48)
Chemical Name
4-(2-((N-(4-chlorobenzyl)-2,3,4,5,6-pentafluorophenyl)sulfonamido)-N-(3,5-di-tert-butylbenzyl)acetamido)benzoic acid
Synonyms
AC4130 AC-4130 AC4-130 AC-4-130
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)
DMSO : ~100 mg/mL (~133.12 mM)
H2O : < 0.1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.3312 mL 6.6560 mL 13.3120 mL
5 mM 0.2662 mL 1.3312 mL 2.6624 mL
10 mM 0.1331 mL 0.6656 mL 1.3312 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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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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.

Biological Data
  • In vitro characterization of AC-4–130. a Chemical structure of AC-4–130. b Schematic representation of the STAT5B domain structure and binding mode of AC-4–130. c 1D 19F NMR studies of AC-4–130 with STAT5B.[1].Bettina Wingelhofer, et al. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia. 2018 May;32(5):1135-1146.
  • AC-4–130 inhibits STAT5 dimerization and target gene expression. a Subcellular fractions of Ba/F3 FLT3-ITD+ cells immunoblotted for pY-STAT5 and total STAT5. α-TUBULIN and LAMIN B1 were used as loading controls for cytoplasmic and nuclear fractions, respectively. Blots represent 2 independent experiments. Uncropped version of the Western blot is shown in Supplementary Fig. 8. b STAT5A-MYC and STAT5A-FLAG were co-transfected into HEK293T cells, co-immunoprecipitated with anti-FLAG and blotted with anti-FLAG and anti-MYC. Whole cell lysates were immunoblotted for MYC- or FLAG-tag, STAT5A, and HSC70 to show input. Results represent two independent experiments. Uncropped version of the Western blot is shown in Supplementary Fig. 8. c Ba/F3 cells were electroporated with Luciferase (Firefly) reporter plasmid for STAT5, and HT-29 cells were transfected with reporter plasmids for STAT1 or STAT3 in addition to pRL-TK (Renilla luciferase). Cells were starved, pretreated with AC-4–130 or DMSO (Ctrl) for 6 h and stimulation with appropriate cytokine. Relative luciferase activity was determined using the Dual-Luciferase Reporter Assay.[1].Bettina Wingelhofer, et al. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia. 2018 May;32(5):1135-1146.
  • FLT3-ITD+ cells are most susceptible to AC-4–130. a Viability assay for hematopoietic or control cell lines with AC-4–130 or DMSO (Ctrl) for 72 h. IC50 values (µM) were determined using GraphPad Prism 5 software (GraphPad Software, Inc.). b MV4–11 and MOLM-13 cells were treated with AC-4–130 or DMSO (Ctrl) in a dose-dependent manner for 72 h or with 5 µM AC-4–130 in a time-dependent manner. Apoptotic cells were detected by AnnexinV/PI staining. Representative dot plots are shown. c Cell cycle distribution was determined after 72 h using PI staining.[1].Bettina Wingelhofer, et al. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia. 2018 May;32(5):1135-1146.
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