(+)-ZK 216348 - CAS 669073-68-1
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C24H23F3N2O5
Molecular Weight:
476.45
COA:
Inquire
Targets:
Glucocorticoid Receptor
Description:
(+)-ZK 216348 is a selective nonsteroidal glucocorticoid receptor (GR) agonist for the treatment of experimental colitis (IC50 values of 20, 20, and 80 nM for GR, Progesterone (PR) and Mineralocorticoid (MR) receptors, respectively). (+)-ZK 216348 exhibits antiinflammatory activity for both systemic and topical application, and shows no negative effects on intestinal epithelial migration or proliferation.
Brife Description:
glucocorticoid receptor (GR) agonist
Purity:
99%
Synonyms:
ZK216348; ZK 216348; ZK-216348; 4-(2,3-dihydro-1-benzofuran-7-yl)-2-hydroxy-4-methyl-N-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-(trifluoromethyl)pentanamide
MSDS:
Inquire
InChIKey:
VRZVKIJRJRBQJT-UHFFFAOYSA-N
InChI:
InChI=1S/C24H23F3N2O5/c1-13-17-11-15(7-8-16(17)20(30)34-29-13)28-21(31)23(32,24(25,26)27)12-22(2,3)18-6-4-5-14-9-10-33-19(14)18/h4-8,11,32H,9-10,12H2,1-3H3,(H,28,31)
Canonical SMILES:
CC1=NOC(=O)C2=C1C=C(C=C2)NC(=O)C(CC(C)(C)C3=CC=CC4=C3OCC4)(C(F)(F)F)O
1.Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells.
Humphrey EL;Williams JH;Davie MW;Marshall MJ Bone. 2006 May;38(5):652-61. Epub 2005 Nov 17.
Glucocorticoids are effective anti-inflammatory and immunosuppressive agents, but their use is often associated with debilitating side effects such as glucocorticoid-induced osteoporosis. Newly developed glucocorticoid analogues such as the so-called dissociated glucocorticoids are potent immunosuppressants and have the potential for fewer side effects. The effects of these new analogues on osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in osteoblastic cells have not been studied. OPG and RANKL are osteoblast-derived proteins pivotal to the regulation of bone mass. RANKL stimulates bone resorption by increasing osteoclast differentiation, activation and survival. OPG is the decoy receptor for RANKL and thus inhibits bone resorption. Here, we show that dexamethasone, prednisolone, deflazacort and the dissociated glucocorticoids, RU24858, RU40066, RU24782, AL438-F1 and ZK216348 significantly inhibit OPG production in two human osteoblastic cell lines (MG63 and hFOB). The potency for OPG inhibition was ligand and cell-type specific. In both cell types, dexamethasone and prednisolone were the most potent ligands inhibiting OPG production with IC(50)s of approximately 0.
2.Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects.
Schäcke H;Schottelius A;Döcke WD;Strehlke P;Jaroch S;Schmees N;Rehwinkel H;Hennekes H;Asadullah K Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):227-32. Epub 2003 Dec 23.
Glucocorticoids (GCs) are the most commonly used antiinflammatory and immunosuppressive drugs. Their outstanding therapeutic effects, however, are often accompanied by severe and sometimes irreversible side effects. For this reason, one goal of research in the GC field is the development of new drugs, which show a reduced side-effect profile while maintaining the antiinflammatory and immunosuppressive properties of classical GCs. GCs affect gene expression by both transactivation and transrepression mechanisms. The antiinflammatory effects are mediated to a major extent via transrepression, while many side effects are due to transactivation. Our aim has been to identify ligands of the GC receptor (GR), which preferentially induce transrepression with little or no transactivating activity. Here we describe a nonsteroidal selective GR-agonist, ZK 216348, which shows a significant dissociation between transrepression and transactivation both in vitro and in vivo. In a murine model of skin inflammation, ZK 216348 showed antiinflammatory activity comparable to prednisolone for both systemic and topical application. A markedly superior side-effect profile was found with regard to increases in blood glucose, spleen involution, and, to a lesser extent, skin atrophy; however, adrenocorticotropic hormone suppression was similar for both compounds.
3.Discovery of quinolines as selective glucocorticoid receptor agonists.
Jaroch S;Berger M;Huwe C;Krolikiewicz K;Rehwinkel H;Schäcke H;Schmees N;Skuballa W Bioorg Med Chem Lett. 2010 Oct 1;20(19):5835-8. doi: 10.1016/j.bmcl.2010.07.125. Epub 2010 Aug 3.
The dissociated glucocorticoid receptor (GR) agonist ZK 216348 is rendered GR-selective over other nuclear hormone receptors through replacing the methylbenzoxazine with a quinoline moiety. Compounds were shown to be efficacious in cell assays with respect to inflammation endpoints, along with reduced activity in a transactivation assay, hinting at an improved therapeutic window over corticosteroids.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Glucocorticoid Receptor Products


CAS 1229096-88-1 GSK 9027

GSK 9027
(CAS: 1229096-88-1)

GSK 9027 is a glucocorticoid receptor agonist (pIC50 = 8) inhibiting production of the proinflammatory mediator IL-6 in vivo. GSK 9027 is used for the treatment...

CAS 3385-03-3 Flunisolide

Flunisolide
(CAS: 3385-03-3)

Flunisolide is a corticosteroid and used for the treatment of allergic rhinitis.

CAS 5534-09-8 Beclomethasone dipropionate

Beclomethasone dipropionate
(CAS: 5534-09-8)

Beclomethasone dipropionate is a potent glucocorticoid steroid used for the treatment of rhinitis and sinusitis.

CAS 76-25-5 Triamcinolone Acetonide

Triamcinolone Acetonide
(CAS: 76-25-5)

Triamcinolone Acetonide is a long-acting synthetic and a more potent type of triamcinolone, about 8 times as effective as prednisone.

CAS 1044535-58-1 PF-04171327

PF-04171327
(CAS: 1044535-58-1)

PF-04171327 is a dissociated agonist of the glucocorticoid receptor (DAGR), which is a selective high-affinity partial agonist of the GR. It has potent anti-inf...

CAS 83-43-2 Methylprednisolone

Methylprednisolone
(CAS: 83-43-2)

Methylprednisolone is a synthetic corticosteroid with anti-inflammatory and immunomodulating properties.

CAS 125-02-0 Prednisolone Sodium Phosphate

Prednisolone Sodium Phosphate
(CAS: 125-02-0)

The disodium phosphate salt form of Prednisolone which has anti-inflammatory and immunsuppressive effect for behaving as a glucocorticoid.

CAS 1245526-82-2 Glucocorticoid receptor agonist

Glucocorticoid receptor agonist
(CAS: 1245526-82-2)

Glucocorticoid receptor agonist is an effective Glucocorticoid receptor agonist and probably has steroid-like anti-inflammatory properties.

Chemical Structure

CAS 669073-68-1 (+)-ZK 216348

Quick Inquiry

Verification code

Featured Items