WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555969
CAS#: 2225836-30-4
Description: ACH-000143 is a Potent and Peripherally Preferred Melatonin Receptor Agonist that Reduces Liver Triglycerides and Steatosis in Diet-Induced Obese Rats. ACH000143 demonstrated subnanomolar potency at MT1/MT2 receptors, high oral bioavailability in rodents, peripherally preferred exposure, and excellent selectivity in a broad panel of targets. Two-month oral administration of ACH000143 in high-fat diet rats led to a reduction in body weight gain similar to dapagliflozin with superior results on hepatic steatosis and triglyceride levels. An early toxicological assessment indicated that ACH000143 was devoid of hERG binding, genotoxicity, and behavioral alterations at doses up to 100 mg/kg p.o., supporting further investigation of this compound as a drug candidate.
MedKoo Cat#: 555969
Name: ACH000143
CAS#: 2225836-30-4
Chemical Formula: C13H16ClN3O3
Exact Mass: 297.088
Molecular Weight: 297.739
Elemental Analysis: C, 52.44; H, 5.42; Cl, 11.91; N, 14.11; O, 16.12
Synonym: ACH-000143; ACH 000143; ACH000143;
IUPAC/Chemical Name: N-(2-[5-Chloro-2,6-dimethoxy-1H-benzimidazol-1-yl]ethyl)acetamide
InChi Key: BVSLRGAPRGQWNC-UHFFFAOYSA-N
InChi Code: InChI=1S/C13H16ClN3O3/c1-8(18)15-4-5-17-11-7-12(19-2)9(14)6-10(11)16-13(17)20-3/h6-7H,4-5H2,1-3H3,(H,15,18)
SMILES Code: CC(NCCN1C2=CC(OC)=C(Cl)C=C2N=C1OC)=O
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
| Biological target: | ACH-000143 is a melatonin receptor agonist, with EC50 values of 0.06 nM and 0.32 nM for MT1 and MT2, respectively. |
| In vitro activity: | TBD |
| In vivo activity: | The rats from the Chow Vehicle group also gained weight steadily, though less rapidly than the ones on HFD. Treatment with compound 10b (ACH000143) (10 and 30 mg/kg) significantly reduced BW gain on days 13 to 32 (p < 0.05) in comparison with the HFD Vehicle control and dapagliflozin (5 mg/kg) on days 2 to 48, 50 to 54, and 56 (p < 0.05). Compared with the HFD Vehicle, 10b significantly reduced the weekly BW gain on weeks 2 (10 and 30 mg/kg, p < 0.01), 3 (30 mg/kg only, p < 0.05), and 7 (10 and 30 mg/kg, p < 0.05), 15a at 30 mg/kg on week 2 (p < 0.05), and dapagliflozin on week 1 (p < 0.001) (Figure 3B). A trend toward significantly reduced BW gain from day 1 to day 57 versus HFD Vehicle was observed for 10b (10 and 30 mg/kg, p = 0.098) and dapagliflozin (p = 0.051). Reference: J Med Chem. 2021 Feb 25;64(4):1904-1929. https://pubmed.ncbi.nlm.nih.gov/33626870/ |
The following data is based on the product molecular weight 297.739 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. Ferreira MA Jr, Azevedo H, Mascarello A, Segretti ND, Russo E, Russo V, Guimarães CRW. Discovery of ACH-000143: A Novel Potent and Peripherally Preferred Melatonin Receptor Agonist that Reduces Liver Triglycerides and Steatosis in Diet-Induced Obese Rats. J Med Chem. 2021 Feb 25;64(4):1904-1929. doi: 10.1021/acs.jmedchem.0c00627. Epub 2021 Feb 8. PMID: 33626870. |
| In vitro protocol: | TBD |
| In vivo protocol: | 1. Ferreira MA Jr, Azevedo H, Mascarello A, Segretti ND, Russo E, Russo V, Guimarães CRW. Discovery of ACH-000143: A Novel Potent and Peripherally Preferred Melatonin Receptor Agonist that Reduces Liver Triglycerides and Steatosis in Diet-Induced Obese Rats. J Med Chem. 2021 Feb 25;64(4):1904-1929. doi: 10.1021/acs.jmedchem.0c00627. Epub 2021 Feb 8. PMID: 33626870. |
Ferreira MA Jr, Azevedo H, Mascarello A, Segretti ND, Russo E, Russo V, Guimarães CRW. Discovery of ACH-000143: A Novel Potent and Peripherally Preferred Melatonin Receptor Agonist that Reduces Liver Triglycerides and Steatosis in Diet-Induced Obese Rats. J Med Chem. 2021 Feb 25;64(4):1904-1929. doi: 10.1021/acs.jmedchem.0c00627. Epub 2021 Feb 8. PMID: 33626870.
