K-7174 diHCl is an orally bioactive inhibitor of proteasome and GATA. K-7174 diHCl inhibits cell adhesion. K-7174 diHCl causes apoptosis. K-7174 diHCl has anti-tumor activity and may be utilized in cancer-related research.

Physicochemical Properties

Molecular Formula	C33H50CL2N2O6
Molecular Weight	641.6659
Exact Mass	568.351
CAS #	191089-60-8
Related CAS #	K-7174;191089-59-5
PubChem CID	9874191
Appearance	White to yellow solid powder
Density	1.1±0.1 g/cm3
Boiling Point	689.9±55.0 °C at 760 mmHg
Flash Point	171.2±28.7 °C
Vapour Pressure	0.0±2.2 mmHg at 25°C
Index of Refraction	1.552
LogP	5.61
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	16
Heavy Atom Count	41
Complexity	663
Defined Atom Stereocenter Count	0
SMILES	COC1=CC(=CC(=C1OC)OC)/C=C/CCCN2CCN(CCC2)CCC/C=C/C3=CC(=C(C(=C3)OC)OC)OC
InChi Key	JXXCDAKRSXICGM-AOEKMSOUSA-N
InChi Code	InChI=1S/C33H48N2O6/c1-36-28-22-26(23-29(37-2)32(28)40-5)14-9-7-11-16-34-18-13-19-35(21-20-34)17-12-8-10-15-27-24-30(38-3)33(41-6)31(25-27)39-4/h9-10,14-15,22-25H,7-8,11-13,16-21H2,1-6H3/b14-9+,15-10+
Chemical Name	1,4-bis[(E)-5-(3,4,5-trimethoxyphenyl)pent-4-enyl]-1,4-diazepane
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	VCAM-1 and its ligands' ability to adhere is inhibited by K-7174 diHClide (10 μM; 1 h) [1]. With an IC50 value of 14 μM, K-7174 diHClide (1-30 μM; 1 h) dose-dependently suppresses VCAM-1 expression [1]. With an IC50 value of 9 μM, K-7174 diHClide (1-30 μM; 1 h) dose-dependently suppresses TNFα activation of VCAM-1 mRNA[1]. In Hep3B cells, K-7174 diHClide (10–20 μM; 24 hours) dose-dependently restores Epo synthesis [2]. K-7174 diHClide decreases GATA binding activity at 2.5–30 μM for 24 hours [2]. K-7174 diHClide (0-25 μM; 72 h) causes apoptosis and suppresses the proliferation of MM cells [3].
ln Vivo	K-7174 diHClide (30 mg/kg; intraperitoneally once daily for 9 days) reverses hemoglobin concentration and reticulocyte count reductions caused by TNF-α or IL-1β [2]. In vivo tumor growth is inhibited by K-7174 dihydrochloride (75 mg/kg; intraperitoneally administered once daily for 14 days) [3]. K-7174 dihydrochloride is more effective than intraperitoneal injection at inhibiting tumor growth in vivo when taken orally once daily for 14 days at a dose of 50 mg/kg [3].
Cell Assay	Cell Viability Assay[3] Cell Types: KMS12-BM, U266 and RPMI8226 Cell line Tested Concentrations: 0-25 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of MM cell growth. Apoptosis analysis [3] Cell Types: KMS12-BM, U266 and RPMI8226 Cell line Tested Concentrations: 10 μM Incubation Duration: 48 h Experimental Results: As the percentage of annexin-V positive cells increased, the apoptosis of MM cells increased Dramatically.
Animal Protocol	Animal/Disease Models: ICR mice injected with IL-β or TNF-α [2] Doses: 30 mg/kg Route of Administration: intraperitoneal (ip) injection; 30 mg/kg, one time/day for 9 days Experimental Results: Erythropoietin (Epo ) yield, reticulocyte count, and hemoglobin (Hb) concentration increased. Animal/Disease Models: NOD/SCID mouse xenograft [3] Doses: 75 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 14 days. Experimental Results: Tumor volume was Dramatically diminished, but body weight was Dramatically diminished after 10 days. Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse with murine xenografts [3] Doses: 50 mg/kg Route of Administration: po (oral gavage); one time/day for 14 days Experimental Results: Demonstrated anti-myeloma activity. Oral administration is more effective than intraperitoneal (ip) injection.
References	[1]. A novel cell adhesion inhibitor, K-7174, reduces the endothelial VCAM-1 induction by inflammatory cytokines, acting through the regulation of GATA. Biochem Biophys Res Commun. 2000 Jun 7;272(2):370-4. [2]. A GATA-specific inhibitor (K-7174) rescues anemia induced by IL-1beta, TNF-alpha, or L-NMMA. FASEB J. 2003 Sep;17(12):1742-4. [3]. The novel orally active proteasome inhibitor K-7174 exerts anti-myeloma activity in vitro and in vivo by down-regulating the expression of class I histone deacetylases. J Biol Chem. 2013 Aug 30;288(35):25593-602.

Solubility Data

Solubility (In Vitro)	H2O : ~15 mg/mL (~23.38 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 10 mg/mL (15.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.5584 mL	7.7922 mL	15.5843 mL
	5 mM	0.3117 mL	1.5584 mL	3.1169 mL
	10 mM	0.1558 mL	0.7792 mL	1.5584 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.