AMG-009 is a novel, potent, orally bioactive, small molecule antagonist of prostaglandin D2, with IC50 of 3 nM and 12 nM for CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) and DP (D prostanoid) receptors, respectively. For the treatment of allergic rhinitis and asthma, AMG 009 was undergoing preclinical development in the US.
Physicochemical Properties
| Molecular Formula | C26H26CL2N2O7S |
| Molecular Weight | 581.4648 |
| Exact Mass | 580.084 |
| Elemental Analysis | C, 53.71; H, 4.51; Cl, 12.19; N, 4.82; O, 19.26; S, 5.51 |
| CAS # | 1027847-67-1 |
| PubChem CID | 10483360 |
| Appearance | White to light brown solid powder |
| LogP | 7.48 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 38 |
| Complexity | 887 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | ClC1C([H])=C(C([H])=C([H])C=1S(N([H])C1C([H])=C(C([H])=C([H])C=1OC1C([H])=C([H])C(C([H])([H])C(=O)O[H])=C([H])C=1OC([H])([H])[H])C(N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)(=O)=O)Cl |
| InChi Key | DKSKRBVXRDGYAS-UHFFFAOYSA-N |
| InChi Code | 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) |
| Chemical Name | 2-[4-[4-(butylcarbamoyl)-2-[(2,4-dichlorophenyl)sulfonylamino]phenoxy]-3-methoxyphenyl]acetic acid |
| Synonyms | AMG-009; AMG 009; AMG009 |
| 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
| Targets | DP ( IC50 = 3 nM ) |
| ln Vitro | AMG-009 prevents PGD2-induced down-modulation of CRTH2 on CD16 negative granulocytes (eosinophils) in human whole blood with a Ki of 1 nM. Additionally, AMG 009 has a Ki of 148 nM against PGD2-induced cAMP response mediated by DP in platelets in 80% of human whole blood. Guinea pig DP receptor-expressing cells (Ki=131 nM) in an assay for PGD2-induced cAMP response are inhibited by AMG 009 (IC50=3 nM)[1]. |
| ln Vivo | AMG 009 (3, 10 or 30 mg/kg, s.c.) in an acute guinea pig model causes a dose-dependent decrease in airway resistance triggered by PGD2 aerosol[1]. AMG 009, with a Kb of 82 nM, dramatically increases DP potency in a guinea pig model of PGD2-induced airway constriction[2]. |
| References |
[1]. Discovery and optimization of CRTH2 and DP dual antagonists. Bioorg Med Chem Lett. 2009 Nov 15;19(22):6419-23. [2]. Discovery of AMG 853, a CRTH2 and DP Dual Antagonist. ACS Med Chem Lett. 2011 Mar 2;2(5):326-30. [3]. Solving time-dependent CYP3A4 inhibition for a series of indole-phenylacetic acid dual antagonists of the PGD(2) receptors CRTH2 and DP. Bioorg Med Chem Lett. 2014 Jul 1;24(13):2877-80. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7198 mL | 8.5990 mL | 17.1981 mL | |
| 5 mM | 0.3440 mL | 1.7198 mL | 3.4396 mL | |
| 10 mM | 0.1720 mL | 0.8599 mL | 1.7198 mL |