K-7174 Free Base | CAS# 191089-59-5 (free base) | 20S proteasome inhibitor

MedKoo Cat#: 414201 | Name: K-7174 Free Base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

K-7174 Free Base is a 20S proteasome inhibitor that inhibits binding of monocytes to cytokine-stimulated endothelial cells.

Chemical Structure

K-7174 Free Base

CAS#191089-59-5 (free base)

Theoretical Analysis

MedKoo Cat#: 414201

Name: K-7174 Free Base

CAS#: 191089-59-5 (free base)

Chemical Formula: C33H48N2O6

Exact Mass: 568.3512

Molecular Weight: 568.76

Elemental Analysis: C, 69.69; H, 8.51; N, 4.93; O, 16.88

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Related CAS #

191089-60-8 (HCl) 191089-59-5 (free base)

Synonym

K-7174 Free Base; K7174; K 7174

IUPAC/Chemical Name

1H-1,4-Diazepine, hexahydro-1,4-bis((4E)-5-(3,4,5-trimethoxyphenyl)-4-penten-1-yl)-

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+

SMILES Code

COC1=C(OC)C(OC)=CC(/C=C/CCCN2CCN(CCC/C=C/C3=CC(OC)=C(OC)C(OC)=C3)CCC2)=C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

K-7174 is an orally active Proteasome and GATA inhibitor.

In vitro activity:

Compound K7174 potentiates the inhibitory effect of simvastatin on the proliferation of DU4475 cells characterized by low expression of ELOVL5-IGFBP6 pair, but not on the proliferation of MDA-MB-231 cells with high expression of these markers. Reference: Bull Exp Biol Med. 2019 Mar;166(5):656-660. https://pubmed.ncbi.nlm.nih.gov/30903492/

In vivo activity:

The intraperitoneal injection of K-7174 alleviated lupus-like symptoms and improved cognitive dysfunction in MRL/lpr mice. Also, it significantly attenuated neuronal degeneration and decreased serum albumin deposition in the hippocampus. Furthermore, K-7174 acted directly on the brain microvascular endothelial bEnd.3 cells and reduced the BBB permeability, manifested by inhibiting the activation of brain microvascular endothelial cells and increasing the expression of tight junctions (TJs). Reference: Brain Res. 2022 Dec 12;1801:148203. https://pubmed.ncbi.nlm.nih.gov/36521514/

Preparing Stock Solutions

The following data is based on the product molecular weight 568.76 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Shkurnikov MY, Poloznikov AA, Nikulin SV, Schumacher U, Wicklein D, Stürken C, Galatenko VV, Alekseev BY. Transcriptome Guided Drug Combination Suppresses Proliferation of Breast Cancer Cells. Bull Exp Biol Med. 2019 Mar;166(5):656-660. doi: 10.1007/s10517-019-04412-4. Epub 2019 Mar 22. PMID: 30903492. 2. Imagawa S, Nakano Y, Obara N, Suzuki N, Doi T, Kodama T, Nagasawa T, Yamamoto M. 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. doi: 10.1096/fj.02-1134fje. Epub 2003 Jul 18. PMID: 12958195. 3. Fan Y, Liu X, Wu J, Ni J, Liang J, Hou Y, Dou H. Small molecule compound K-7174 attenuates neuropsychiatric manifestations in lupus-prone mice. Brain Res. 2022 Dec 12;1801:148203. doi: 10.1016/j.brainres.2022.148203. Epub ahead of print. PMID: 36521514. 4. Fujiwara T, Ikeda T, Nagasaka Y, Okitsu Y, Katsuoka Y, Fukuhara N, Onishi Y, Ishizawa K, Ichinohasama R, Tomosugi N, Harigae H. A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568. doi: 10.1371/journal.pone.0075568. PMID: 24086573; PMCID: PMC3785497.

In vitro protocol:

In vivo protocol:

1. Fan Y, Liu X, Wu J, Ni J, Liang J, Hou Y, Dou H. Small molecule compound K-7174 attenuates neuropsychiatric manifestations in lupus-prone mice. Brain Res. 2022 Dec 12;1801:148203. doi: 10.1016/j.brainres.2022.148203. Epub ahead of print. PMID: 36521514. 2. Fujiwara T, Ikeda T, Nagasaka Y, Okitsu Y, Katsuoka Y, Fukuhara N, Onishi Y, Ishizawa K, Ichinohasama R, Tomosugi N, Harigae H. A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568. doi: 10.1371/journal.pone.0075568. PMID: 24086573; PMCID: PMC3785497.

1: Kikuchi J, Yamada S, Koyama D, Wada T, Nobuyoshi M, Izumi T, Akutsu M, Kano Y, Furukawa Y. 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):25593-25602. doi: 10.1074/jbc.M113.480574. Epub 2013 Jul 22. PMID: 23878197; PMCID: PMC3757220. 2: Imagawa S, Nakano Y, Obara N, Suzuki N, Doi T, Kodama T, Nagasawa T, Yamamoto M. 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. doi: 10.1096/fj.02-1134fje. Epub 2003 Jul 18. PMID: 12958195. 3: Takano Y, Hiramatsu N, Okamura M, Hayakawa K, Shimada T, Kasai A, Yokouchi M, Shitamura A, Yao J, Paton AW, Paton JC, Kitamura M. Suppression of cytokine response by GATA inhibitor K-7174 via unfolded protein response. Biochem Biophys Res Commun. 2007 Aug 24;360(2):470-5. doi: 10.1016/j.bbrc.2007.06.082. Epub 2007 Jun 26. PMID: 17604001. 4: Shimada T, Hiramatsu N, Okamura M, Hayakawa K, Kasai A, Yao J, Kitamura M. Unexpected blockade of adipocyte differentiation by K-7174: implication for endoplasmic reticulum stress. Biochem Biophys Res Commun. 2007 Nov 16;363(2):355-60. doi: 10.1016/j.bbrc.2007.08.167. Epub 2007 Sep 6. PMID: 17869220. 5: Umetani M, Nakao H, Doi T, Iwasaki A, Ohtaka M, Nagoya T, Mataki C, Hamakubo T, Kodama T. 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. doi: 10.1006/bbrc.2000.2784. PMID: 10833420. 6: Nakano Y, Imagawa S, Matsumoto K, Stockmann C, Obara N, Suzuki N, Doi T, Kodama T, Takahashi S, Nagasawa T, Yamamoto M. Oral administration of K-11706 inhibits GATA binding activity, enhances hypoxia-inducible factor 1 binding activity, and restores indicators in an in vivo mouse model of anemia of chronic disease. Blood. 2004 Dec 15;104(13):4300-7. doi: 10.1182/blood-2004-04-1631. Epub 2004 Aug 24. PMID: 15328158. 7: Kikuchi J, Shibayama N, Yamada S, Wada T, Nobuyoshi M, Izumi T, Akutsu M, Kano Y, Sugiyama K, Ohki M, Park SY, Furukawa Y. Homopiperazine derivatives as a novel class of proteasome inhibitors with a unique mode of proteasome binding. PLoS One. 2013 Apr 11;8(4):e60649. doi: 10.1371/journal.pone.0060649. PMID: 23593271; PMCID: PMC3623906. 8: Fujiwara T, Ikeda T, Nagasaka Y, Okitsu Y, Katsuoka Y, Fukuhara N, Onishi Y, Ishizawa K, Ichinohasama R, Tomosugi N, Harigae H. A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568. doi: 10.1371/journal.pone.0075568. PMID: 24086573; PMCID: PMC3785497.