A-922500
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MedKoo CAT#: 526700

CAS#: 959122-11-3

Description: A-922500 is a potent orally active inhibitor of DGAT-1 activity, inhibiting both human and mouse forms of the enzymes with IC50 values of 7 and 24 nM, respectively. Acyl CoA/diacylglycerol acyltransferase (DGAT) 1 is one of two known DGAT enzymes that catalyze the final and only committed step in triglyceride biosynthesis.


Chemical Structure

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A-922500
CAS# 959122-11-3

Theoretical Analysis

MedKoo Cat#: 526700
Name: A-922500
CAS#: 959122-11-3
Chemical Formula: C26H24N2O4
Exact Mass: 428.1736
Molecular Weight: 428.488
Elemental Analysis: C, 72.88; H, 5.65; N, 6.54; O, 14.94

Price and Availability

Size Price Availability Quantity
25.0mg USD 450.0 2 Weeks
50.0mg USD 750.0 2 Weeks
100.0mg USD 1250.0 2 Weeks
200.0mg USD 1950.0 2 Weeks
500.0mg USD 3650.0 2 Weeks
1.0g USD 4250.0 2 Weeks
2.0g USD 7650.0 2 Weeks
Bulk inquiry

Synonym: A-922500; A 922500; A922500.

IUPAC/Chemical Name: (1R,2R)-2-(4'-(3-phenylureido)-[1,1'-biphenyl]-4-carbonyl)cyclopentane-1-carboxylic acid

InChi Key: BOZRFEQDOFSZBV-DHIUTWEWSA-N

InChi Code: InChI=1S/C26H24N2O4/c29-24(22-7-4-8-23(22)25(30)31)19-11-9-17(10-12-19)18-13-15-21(16-14-18)28-26(32)27-20-5-2-1-3-6-20/h1-3,5-6,9-16,22-23H,4,7-8H2,(H,30,31)(H2,27,28,32)/t22-,23-/m1/s1

SMILES Code: O=C(NC1=CC=CC=C1)NC2=CC=C(C=C2)C3=CC=C(C=C3)C([C@@H]4CCC[C@H]4C(O)=O)=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: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

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

Product Data:

Biological target: A 922500 (DGAT-1 Inhibitor 4a) is a diacylglycerol acyltransferase 1 (DGAT-1) inhibitor with IC50s of 9 and 22 nM against human and mouse DGAT-1, respectively.
In vitro activity: As shown by the representative images (Fig 2A) and quantification (Fig 2B and 2C), treatment with A922500 inhibited the LD formation triggered by SARS-CoV-2 infection in A549 human epithelial cells and in primary human monocytes in a dose dependent manner, with 50% effective concentration (EC50) value of 0.108 μM for A549 cells and 0.711 μM for human monocytes. To gain insights on the functions of LDs in SARS-CoV-2 infection, LD biogenesis was inhibited by A922500, a DGAT-1 inhibitor. Treatment with A922500 significantly reduced the viral load in human primary monocytes in a dose dependent way (Fig 3A), suggesting a role for DGAT-1 and LD in SARS-CoV-2 replication. Reference: PLoS Pathog. 2020 Dec; 16(12): e1009127. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773323/
In vivo activity: The effect of DGAT-1 inhibitor A-922500 (0.03, 0.3 and 3 mg/kg) on postprandial hyperlipidemia in mice, assessed 2 h after an oral corn oil bolus, is shown in Fig. 5. Consistent with the findings in the time-course studies described above, serum triglyceride concentrations significantly increased 2 h after corn oil administration in vehicle pretreated C57BL/6 (2.0-fold), ob/ob (2.5-fold), apoE−/− (1.8-fold) and CD-1 (3.5-fold) mice. DGAT-1 inhibition produced dose-dependent reductions in post corn oil serum triglyceride concentrations in all mice. The apoE−/− mice appeared most sensitive to DGAT-1 inhibition as A-922500 administered at 0.03 mg/kg significantly attenuated the postprandial triglyceride response by 79%, whereas this dose had no statistically significant effect on the response of serum triglyceride concentrations to corn oil in C57BL/6, ob/ob or CD-1 mice. A-922500 dosed at 0.3 mg/kg significantly inhibited the postprandial serum triglyceride response to corn oil in C57BL/6 (99%), ob/ob (85%), apoE−/− (116%) and CD-1 (90%) mice, and when dosed at 3 mg/kg essentially abolished the postprandial hyperlipidemia induced by corn oil in C57BL/6 (92%), ob/ob (107%), apoE−/− (101%) and CD-1 (103%) mice. Reference: Eur J Pharmacol. 2010 Jul 10;637(1-3):155-61. https://pubmed.ncbi.nlm.nih.gov/20385122/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 44.36 103.53
DMSO:PBS (pH 7.2) (1:10) 0.1 0.23
DMF 20.0 46.68
Ethanol 0.2 0.47

Preparing Stock Solutions

The following data is based on the product molecular weight 428.488 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.

Recalculate based on batch purity %
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. Huang JS, Guo BB, Wang GH, Zeng LM, Hu YH, Wang T, Wang HY. DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis. Acta Pharmacol Sin. 2021 Feb;42(2):264-271. doi: 10.1038/s41401-020-0482-7. Epub 2020 Jul 31. PMID: 32737468; PMCID: PMC8027676. 2. Dias SSG, Soares VC, Ferreira AC, Sacramento CQ, Fintelman-Rodrigues N, Temerozo JR, Teixeira L, Nunes da Silva MA, Barreto E, Mattos M, de Freitas CS, Azevedo-Quintanilha IG, Manso PPA, Miranda MD, Siqueira MM, Hottz ED, Pão CRR, Bou-Habib DC, Barreto-Vieira DF, Bozza FA, Souza TML, Bozza PT. Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators. PLoS Pathog. 2020 Dec 16;16(12):e1009127. doi: 10.1371/journal.ppat.1009127. PMID: 33326472; PMCID: PMC7773323. 3. Tsuda N, Kumadaki S, Higashi C, Ozawa M, Shinozaki M, Kato Y, Hoshida K, Kikuchi S, Nakano Y, Ogawa Y, Furusako S. Intestine-targeted DGAT1 inhibition improves obesity and insulin resistance without skin aberrations in mice. PLoS One. 2014 Nov 18;9(11):e112027. doi: 10.1371/journal.pone.0112027. PMID: 25405858; PMCID: PMC4236014. 4. King AJ, Segreti JA, Larson KJ, Souers AJ, Kym PR, Reilly RM, Collins CA, Voorbach MJ, Zhao G, Mittelstadt SW, Cox BF. In vivo efficacy of acyl CoA: diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia. Eur J Pharmacol. 2010 Jul 10;637(1-3):155-61. doi: 10.1016/j.ejphar.2010.03.056. Epub 2010 Apr 10. PMID: 20385122.
In vitro protocol: 1. Huang JS, Guo BB, Wang GH, Zeng LM, Hu YH, Wang T, Wang HY. DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis. Acta Pharmacol Sin. 2021 Feb;42(2):264-271. doi: 10.1038/s41401-020-0482-7. Epub 2020 Jul 31. PMID: 32737468; PMCID: PMC8027676. 2. Dias SSG, Soares VC, Ferreira AC, Sacramento CQ, Fintelman-Rodrigues N, Temerozo JR, Teixeira L, Nunes da Silva MA, Barreto E, Mattos M, de Freitas CS, Azevedo-Quintanilha IG, Manso PPA, Miranda MD, Siqueira MM, Hottz ED, Pão CRR, Bou-Habib DC, Barreto-Vieira DF, Bozza FA, Souza TML, Bozza PT. Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators. PLoS Pathog. 2020 Dec 16;16(12):e1009127. doi: 10.1371/journal.ppat.1009127. PMID: 33326472; PMCID: PMC7773323.
In vivo protocol: 1. Tsuda N, Kumadaki S, Higashi C, Ozawa M, Shinozaki M, Kato Y, Hoshida K, Kikuchi S, Nakano Y, Ogawa Y, Furusako S. Intestine-targeted DGAT1 inhibition improves obesity and insulin resistance without skin aberrations in mice. PLoS One. 2014 Nov 18;9(11):e112027. doi: 10.1371/journal.pone.0112027. PMID: 25405858; PMCID: PMC4236014. 2. King AJ, Segreti JA, Larson KJ, Souers AJ, Kym PR, Reilly RM, Collins CA, Voorbach MJ, Zhao G, Mittelstadt SW, Cox BF. In vivo efficacy of acyl CoA: diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia. Eur J Pharmacol. 2010 Jul 10;637(1-3):155-61. doi: 10.1016/j.ejphar.2010.03.056. Epub 2010 Apr 10. PMID: 20385122.

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1: Tsuda N, Kumadaki S, Higashi C, Ozawa M, Shinozaki M, Kato Y, Hoshida K,
Kikuchi S, Nakano Y, Ogawa Y, Furusako S. Intestine-targeted DGAT1 inhibition
improves obesity and insulin resistance without skin aberrations in mice. PLoS
One. 2014 Nov 18;9(11):e112027. doi: 10.1371/journal.pone.0112027. eCollection
2014. PubMed PMID: 25405858; PubMed Central PMCID: PMC4236014.

2: King AJ, Segreti JA, Larson KJ, Souers AJ, Kym PR, Reilly RM, Collins CA,
Voorbach MJ, Zhao G, Mittelstadt SW, Cox BF. In vivo efficacy of acyl CoA:
diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of
postprandial hyperlipidemia. Eur J Pharmacol. 2010 Jul 10;637(1-3):155-61. doi:
10.1016/j.ejphar.2010.03.056. Epub 2010 Apr 10. PubMed PMID: 20385122.

3: King AJ, Segreti JA, Larson KJ, Souers AJ, Kym PR, Reilly RM, Zhao G,
Mittelstadt SW, Cox BF. Diacylglycerol acyltransferase 1 inhibition lowers serum
triglycerides in the Zucker fatty rat and the hyperlipidemic hamster. J Pharmacol
Exp Ther. 2009 Aug;330(2):526-31. doi: 10.1124/jpet.109.154047. Epub 2009 May 28.
PubMed PMID: 19478132.

A-922500

25.0mg / USD 450.0