AMG-009 - CAS 1027847-67-1
Catalog number: 1027847-67-1
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C26H26Cl2N2O7S
Molecular Weight:
581.46
COA:
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Targets:
CRTH2 (GPR44)
Description:
AMG-009 is an orally active, small molecule dual D prostanoid(DP) receptor and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist. It was in preclinical development for the treatment of asthma and allergic rhinitis. It was developed by Amgen Inc.
Purity:
>98 %
Appearance:
Solid powder
Synonyms:
2-[4-[4-(Butylcarbamoyl)-2-[(2,4-dichlorophenyl)sulfonylamino]phenoxy]-3-methoxyphenyl]acetic acid;AMG009;Benzeneacetic acid, 4-(4-((butylamino)carbonyl)-2-(((2,4-dichlorophenyl)sulfonyl)amino)phenoxy)-3-methoxy-
Solubility:
10 mM in DMSO
Storage:
-20°C Freezer
MSDS:
Inquire
Application:
AMG-009 was in preclinical development for the treatment of asthma and allergic rhinitis.
Quality Standard:
In-house standard
Shelf Life:
2 month in rt, long time
Quantity:
Milligrams-Grams
Melting Point:
148.6 °C
Density:
1.403±0.06 g/cm3 | Condition: Temp: 20 °C Press: 760 Torr
InChIKey:
DKSKRBVXRDGYAS-UHFFFAOYSA-N
InChI:
InChI=1S/C26H26Cl2N2O7S/c1-3-4-11-29-26(33)17-6-9-21(37-22-8-5-16(13-25(31)32)12-23(22)36-2)20(14-17)30-38(34,35)24-10-7-18(27)15-19(24)28/h5-10,12,14-15,30H,3-4,11,13H2,1-2H3,(H,29,33)(H,31,32)
Canonical SMILES:
CCCCNC(=O)C1=CC(=C(C=C1)OC2=C(C=C(C=C2)CC(=O)O)OC)NS(=O)(=O)C3=C(C=C(C=C3)Cl)Cl
Current Developer:
AMG-009 was developed by Amgen Inc.
1.Discovery of AMG 853, a CRTH2 and DP Dual Antagonist.
Liu J;Li AR;Wang Y;Johnson MG;Su Y;Shen W;Wang X;Lively S;Brown M;Lai S;Gonzalez Lopez De Turiso F;Xu Q;Van Lengerich B;Schmitt M;Fu Z;Sun Y;Lawlis S;Seitz L;Danao J;Wait J;Ye Q;Tang HL;Grillo M;Collins TL;Sullivan TJ;Medina JC ACS Med Chem Lett. 2011 Mar 2;2(5):326-30. doi: 10.1021/ml1002234. eCollection 2011 May 12.
Prostaglandin D2 (PGD2) plays a key role in mediating allergic reactions seen in asthma, allergic rhinitis, and atopic dermatitis. PGD2 exerts its activity through two G protein-coupled receptors (GPCRs), prostanoid D receptor (DP or DP1), and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 or DP2). We report the optimization of a series of phenylacetic acid derivatives in an effort to improve the dual activity of AMG 009 against DP and CRTH2. These efforts led to the discovery of AMG 853 (2-(4-(4-(tert-butylcarbamoyl)-2-(2-chloro-4-cyclopropylphenyl sulfonamido)phenoxy)-5-chloro-2-fluorophenyl)acetic acid), which is being evaluated in human clinical trials for asthma.
2.Enhancing and sustaining AMG 009 dissolution from a matrix tablet via microenvironmental pH modulation and supersaturation.
Bi M;Kyad A;Kiang YH;Alvarez-Nunez F;Alvarez F AAPS PharmSciTech. 2011 Dec;12(4):1157-62. doi: 10.1208/s12249-011-9679-x. Epub 2011 Sep 13.
The objective of this study was to investigate the combined effect of pH modifiers and nucleation inhibitors on enhancing and sustaining the dissolution of AMG 009 tablet via supersaturation. Several bases and polymers were added as pH modifiers and nucleation inhibitors, respectively, to evaluate their impact on the dissolution of AMG 009 tablets. The results indicate that sodium carbonate, among the bases investigated, enhanced AMG 009 dissolution the most. HPMC E5 LV, among the nucleation inhibitors tested, was the most effective in sustaining AMG 009 supersaturation. The release of AMG 009 went from 4% for tablets which did not contain both sodium carbonate and HPMC E5 LV to 70% for the ones that did, resulting in a 17.5-fold increase in the extent of dissolution. The effect of compression force and disintegrant on the dissolution of tablets were also evaluated. The results indicate that compression force had no effect on AMG 009 release. The addition of disintegrating agents, on the other hand, decreased the dissolution of AMG 009.
3.Intravital Multiphoton Microscopy with Fluorescent Bile Salts in Rats as an In Vivo Biomarker for Hepatobiliary Transport Inhibition.
Ryan J;Morgan RE;Chen Y;Volak LP;Dunn RT 2nd;Dunn KW Drug Metab Dispos. 2018 May;46(5):704-718. doi: 10.1124/dmd.117.079277. Epub 2018 Feb 21.
The bile salt export pump (BSEP) is expressed at the canalicular domain of hepatocytes, where it mediates the elimination of monovalent bile salts into the bile. Inhibition of BSEP is considered a susceptibility factor for drug-induced liver injury that often goes undetected during nonclinical testing. Although in vitro assays exist for screening BSEP inhibition, a reliable and specific method for confirming Bsep inhibition in vivo would be a valuable follow up to a BSEP screening strategy, helping to put a translatable context around in vitro inhibition data, incorporating processes such as metabolism, protein binding, and other exposure properties that are lacking in most in vitro BSEP models. Here, we describe studies in which methods of quantitative intravital microscopy were used to identify dose-dependent effects of two known BSEP/Bsep inhibitors, 2-[4-[4-(butylcarbamoyl)-2-[(2,4-dichlorophenyl)sulfonylamino]phenoxy]-3-methoxyphenyl]acetic acid (AMG-009) and bosentan, on hepatocellular transport of the fluorescent bile salts cholylglycyl amidofluorescein and cholyl-lysyl-fluorescein in rats. Results of these studies demonstrate that the intravital microscopy approach is capable of detecting Bsep inhibition at drug doses well below those found to increase serum bile acid levels, and also indicate that basolateral efflux transporters play a significant role in preventing cytosolic accumulation of bile acids under conditions of Bsep inhibition in rats.
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