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).

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)

Biological Activity

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.

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.