WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 558725
CAS#: 147776-06-5
Description: L-161982 is a selective inhibitor of the EP4 PGE2 receptor which enhances oxaliplatin-induced apoptosis in OXR cells, reduces expression of the colonic stem cell markers, CD133 and CD44, and inhibits tumor sphere formation.
MedKoo Cat#: 558725
Name: L-161982
CAS#: 147776-06-5
Chemical Formula: C32H29F3N4O4S2
Exact Mass: 654.1582
Molecular Weight: 654.7232
Elemental Analysis: C, 58.70; H, 4.46; F, 8.71; N, 8.56; O, 9.77; S, 9.79
Synonym: L 161982; L161982; L-161982
IUPAC/Chemical Name: N-[2-[4-[[3-Butyl-5-oxo-1-[2-(trifluoromethyl)phenyl]-1,2,4-triazol-4-yl]methyl]phenyl]phenyl]sulfonyl-3-methylthiophene-2-carboxamide
InChi Key: MMDNKTXNUZFVKD-UHFFFAOYSA-N
InChi Code: InChI=1S/C32H29F3N4O4S2/c1-3-4-13-28-36-39(26-11-7-6-10-25(26)32(33,34)35)31(41)38(28)20-22-14-16-23(17-15-22)24-9-5-8-12-27(24)45(42,43)37-30(40)29-21(2)18-19-44-29/h5-12,14-19H,3-4,13,20H2,1-2H3,(H,37,40)
SMILES Code: O=C(C1=C(C)C=CS1)NS(=O)(C2=CC=CC=C2C3=CC=C(CN4C(CCCC)=NN(C5=CC=CC=C5C(F)(F)F)C4=O)C=C3)=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
Shelf Life: >3 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
| Biological target: | L-161982 is a selective EP4 receptor antagonist. |
| In vitro activity: | The EP4 receptor agonist, PGE1-OH, could mimick PGE2 rescued the inhibitory effect of celecoxib and induced cell growth via ERK phosphorylation, and the EP4 receptor antagonist, L-161,982, completely blocked PGE2-stimulated ERK phosphorylation and proliferation of Tca8113 cells. Furthermore, L-161,982 may induce apoptosis and block cell cycle progression at s phase by upregulating Bax and p21 protein levels and by downregulating Bcl-2, CDK2, and cyclin A2 protein levels. Reference: J Oral Pathol Med. 2017 Nov;46(10):991-997. https://pubmed.ncbi.nlm.nih.gov/28342204/ |
| In vivo activity: | CIA (collagen-induced arthritis) mice treated with L161982 showed reduced arthritis scores, joint swellings, cracked cartilage surface, and less hyperplasia in the connective tissue of the articular cavity. Plasma and tissue IL-17 and MCP-1 decreased, while the proportion of Treg cells is increased both in the spleen and lymph nodes of CIA mice. Reference: BMC Musculoskelet Disord. 2017 Nov 16;18(1):462. https://pubmed.ncbi.nlm.nih.gov/29145862/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 20.0 | 30.55 | |
| DMSO | 37.74 | 57.64 |
The following data is based on the product molecular weight 654.7232 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. Li X, Yang B, Han G, Li W. The EP4 antagonist, L-161,982, induces apoptosis, cell cycle arrest, and inhibits prostaglandin E2-induced proliferation in oral squamous carcinoma Tca8113 cells. J Oral Pathol Med. 2017 Nov;46(10):991-997. doi: 10.1111/jop.12572. Epub 2017 Apr 11. PMID: 28342204. 2. Cherukuri DP, Chen XB, Goulet AC, Young RN, Han Y, Heimark RL, Regan JW, Meuillet E, Nelson MA. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells. Exp Cell Res. 2007 Aug 15;313(14):2969-79. doi: 10.1016/j.yexcr.2007.06.004. Epub 2007 Jun 22. PMID: 17631291; PMCID: PMC2706013. 3. Liu S, Wang Q, Li Z, Ma L, Li T, Li Y, Wang N, Liu C, Xue P, Wang C. TRPV1 Channel Activated by the PGE2/EP4 Pathway Mediates Spinal Hypersensitivity in a Mouse Model of Vertebral Endplate Degeneration. Oxid Med Cell Longev. 2021 Aug 21;2021:9965737. doi: 10.1155/2021/9965737. PMID: 34471470; PMCID: PMC8405310. 4. Chen L, Wu X, Zhong J, Li D. L161982 alleviates collagen-induced arthritis in mice by increasing Treg cells and down-regulating Interleukin-17 and monocyte-chemoattractant protein-1 levels. BMC Musculoskelet Disord. 2017 Nov 16;18(1):462. doi: 10.1186/s12891-017-1819-3. PMID: 29145862; PMCID: PMC5691865. |
| In vitro protocol: | 1. Li X, Yang B, Han G, Li W. The EP4 antagonist, L-161,982, induces apoptosis, cell cycle arrest, and inhibits prostaglandin E2-induced proliferation in oral squamous carcinoma Tca8113 cells. J Oral Pathol Med. 2017 Nov;46(10):991-997. doi: 10.1111/jop.12572. Epub 2017 Apr 11. PMID: 28342204. 2. Cherukuri DP, Chen XB, Goulet AC, Young RN, Han Y, Heimark RL, Regan JW, Meuillet E, Nelson MA. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells. Exp Cell Res. 2007 Aug 15;313(14):2969-79. doi: 10.1016/j.yexcr.2007.06.004. Epub 2007 Jun 22. PMID: 17631291; PMCID: PMC2706013. |
| In vivo protocol: | 1. Liu S, Wang Q, Li Z, Ma L, Li T, Li Y, Wang N, Liu C, Xue P, Wang C. TRPV1 Channel Activated by the PGE2/EP4 Pathway Mediates Spinal Hypersensitivity in a Mouse Model of Vertebral Endplate Degeneration. Oxid Med Cell Longev. 2021 Aug 21;2021:9965737. doi: 10.1155/2021/9965737. PMID: 34471470; PMCID: PMC8405310. 2. Chen L, Wu X, Zhong J, Li D. L161982 alleviates collagen-induced arthritis in mice by increasing Treg cells and down-regulating Interleukin-17 and monocyte-chemoattractant protein-1 levels. BMC Musculoskelet Disord. 2017 Nov 16;18(1):462. doi: 10.1186/s12891-017-1819-3. PMID: 29145862; PMCID: PMC5691865. |
1: Yang L, Wei Y, Luo Y, Yang Q, Li H, Hu C, Yang Y, Yang J. Effect of PGE(2)-EP(s) pathway on primary cultured rat neuron injury caused by aluminum. Oncotarget. 2017 Sep 21;8(54):92004-92017. doi: 10.18632/oncotarget.21122. eCollection 2017 Nov 3. PubMed PMID: 29190893; PubMed Central PMCID: PMC5696159.
2: Chen L, Wu X, Zhong J, Li D. L161982 alleviates collagen-induced arthritis in mice by increasing Treg cells and down-regulating Interleukin-17 and monocyte-chemoattractant protein-1 levels. BMC Musculoskelet Disord. 2017 Nov 16;18(1):462. doi: 10.1186/s12891-017-1819-3. PubMed PMID: 29145862; PubMed Central PMCID: PMC5691865.
3: Gonzalez AA, Salinas-Parra N, Leach D, Navar LG, Prieto MC. PGE(2) upregulates renin through E-prostanoid receptor 1 via PKC/cAMP/CREB pathway in M-1 cells. Am J Physiol Renal Physiol. 2017 Oct 1;313(4):F1038-F1049. doi: 10.1152/ajprenal.00194.2017. Epub 2017 Jul 12. PubMed PMID: 28701311; PubMed Central PMCID: PMC5668586.
4: Cuppoletti J, Tewari KP, Chakrabarti J, Malinowska DH. Identification of the fatty acid activation site on human ClC-2. Am J Physiol Cell Physiol. 2017 Jun 1;312(6):C707-C723. doi: 10.1152/ajpcell.00267.2016. Epub 2017 Apr 19. PubMed PMID: 28424169.
5: Li X, Yang B, Han G, Li W. The EP4 antagonist, L-161,982, induces apoptosis, cell cycle arrest, and inhibits prostaglandin E2-induced proliferation in oral squamous carcinoma Tca8113 cells. J Oral Pathol Med. 2017 Nov;46(10):991-997. doi: 10.1111/jop.12572. Epub 2017 Apr 11. PubMed PMID: 28342204.
6: Wang R, Zhang W, Dong Z, Qi Y, Hultström M, Zhou X, Lai EY. c-Jun N-terminal Kinase mediates prostaglandin-induced sympathoexcitation in rats with chronic heart failure by reducing GAD1 and GABRA1 expression. Acta Physiol (Oxf). 2017 Feb;219(2):494-509. doi: 10.1111/apha.12758. Epub 2016 Aug 12. PubMed PMID: 27439062.
7: Li N, Zhang L, An Y, Zhang L, Song Y, Wang Y, Tang H. Antagonist of prostaglandin E2 receptor 4 induces metabolic alterations in liver of mice. J Proteome Res. 2015 Mar 6;14(3):1566-73. doi: 10.1021/pr501236y. Epub 2015 Feb 23. PubMed PMID: 25669961.
8: Wang F, Lu X, Peng K, Du Y, Zhou SF, Zhang A, Yang T. Prostaglandin E-prostanoid4 receptor mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla. Hypertension. 2014 Aug;64(2):369-77. doi: 10.1161/HYPERTENSIONAHA.114.03654. Epub 2014 May 27. PubMed PMID: 24866147; PubMed Central PMCID: PMC4445967.
9: Stanley CP, O'Sullivan SE. Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries. Pharmacol Res. 2014 Mar;81:74-82. doi: 10.1016/j.phrs.2014.02.001. Epub 2014 Feb 16. PubMed PMID: 24548820; PubMed Central PMCID: PMC3992009.
10: FitzPatrick M, Donovan C, Bourke JE. Prostaglandin E2 elicits greater bronchodilation than salbutamol in mouse intrapulmonary airways in lung slices. Pulm Pharmacol Ther. 2014 Jun;28(1):68-76. doi: 10.1016/j.pupt.2013.11.005. Epub 2013 Nov 28. PubMed PMID: 24291048.
11: Yan G, Wang Q, Shi H, Han Y, Ma G, Tang C, Gu Y. Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia. PLoS One. 2013 Aug 27;8(8):e73839. doi: 10.1371/journal.pone.0073839. eCollection 2013. PubMed PMID: 24013220; PubMed Central PMCID: PMC3754945.
