WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H100065
CAS#: 170729-80-3
Description: Aprepitant is a small molecule, high-affinity substance P antagonist (SPA) with antiemetic activity. Crossing the blood brain barrier, aprepitant binds selectively to the human substance P/neurokinin 1 receptor in the central nervous system (CNS), thereby inhibiting receptor binding of endogenous substance P and substance P-induced emesis. This agent has little or no affinity for serotonin type 3 (5-HT3), dopamine, and corticosteroid receptors.
Hodoodo Cat#: H100065
Name: Aprepitant
CAS#: 170729-80-3
Chemical Formula: C23H21F7N4O3
Exact Mass: 534.15
Molecular Weight: 534.430
Elemental Analysis: C, 51.69; H, 3.96; F, 24.88; N, 10.48; O, 8.98
Synonym: MK0869; MK 0869; MK-0869; ONO7436; ONO-7436; ONO 7436; L754030; L-754030; L 754030; Aprepitant; US brand name: Emend
IUPAC/Chemical Name: 5-(((2R,3S)-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)morpholino)methyl)-1H-1,2,4-triazol-3(2H)-one
InChi Key: ATALOFNDEOCMKK-OITMNORJSA-N
InChi Code: InChI=1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19+,20-/m1/s1
SMILES Code: O=C1NNC(CN2[C@@H](C3=CC=C(F)C=C3)[C@@H](O[C@@H](C4=CC(C(F)(F)F)=CC(C(F)(F)F)=C4)C)OCC2)=N1
Appearance: white solid powder
Purity: >99% (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
More Info: Aprepitant is a white to off-white crystalline solid, with a molecular weight of 534.43. It is practically insoluble in water. Aprepitant is sparingly soluble in ethanol and isopropyl acetate and slightly soluble in acetonitrile. Each capsule of EMEND for oral administration contains either 40 mg, 80 mg, or 125 mg of aprepitant and the following inactive ingredients: sucrose, microcrystalline cellulose, hydroxypropyl cellulose and sodium lauryl sulfate. The capsule shell excipients are gelatin, titanium dioxide, and may contain sodium lauryl sulfate and silicon dioxide. The 40-mg capsule shell also contains yellow ferric oxide, and the 125-mg capsule also contains red ferric oxide and yellow ferric oxide. Mechanism of Action Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupies brain NK 1 receptors. Animal and human studies show that aprepitant augments the antiemetic activity of the 5-HT3 receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both the acute and delayed phases of cisplatin-induced emesis.
| Biological target: | Aprepitant (MK-0869) is a selective and high-affinity neurokinin 1 receptor antagonist with a Kd of 86 pM. |
| In vitro activity: | Aprepitant treatment decreased the levels of ROS and MDA obviously. These findings suggested that aprepitant could protect macrophages by inhibiting oxidative stress. Furthermore, activated macrophages induced by LPS released various pro-inflammatory cytokines and chemokines such as MCP-1 and TNF-α. Excessive production of these factors takes an important part in affecting the development of inflammation. TNF-α is described as a primary inflammatory regulator in the pathogenesis of inflammation. For example, TNF-α is consumedly increased in synovial tissue in rheumatoid arthritis (RA). Interestingly, overexpression of NOX-4 has also been associated with the upregulation of TNF-α. In this study, the expression of these pro-inflammatory factors was decreased significantly by aprepitant. In addition, LPS stimulation activates COX-2 and iNOS transcription which lead to the overexpression of PGE2 and NO in macrophages, respectively. These inflammatory mediators are highly increased in inflammation. The results in this study show that aprepitant reduced PGE2 and NO production induced by LPS, due to its inhibition on the production of COX-2 and iNOS. Reference: Drug Des Devel Ther. 2020; 14: 1943–1952. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246327/ |
| In vivo activity: | Analysis of mRNA expression in the dura mater and spinal cord within the cervical region revealed that expression of mRNA encoding CXCL13, CCL2, and IL-17A was significantly elevated at 2 weeks following B. burgdorferi administration (Fig. 4a–c), while levels of mRNA encoding IL-6 were higher at 4 weeks following infection (Fig. 4d). Similarly, levels of mRNA encoding IL-17A were higher in thoracic region dura mater and spinal cord at 2 weeks following B. burgdorferi challenge (Fig. 4e). Importantly, daily treatment with aprepitant significantly attenuated these infection-associated increases in inflammatory mediator mRNA expression (Fig. 4). Reference: J Neuroinflammation. 2017; 14: 37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312540/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 69.1 | 129.32 | |
| Ethanol | 11.1 | 20.79 | |
| DMF | 25.0 | 46.78 | |
| DMF:PBS (pH 7.2) (1:2) | 0.3 | 0.62 |
The following data is based on the product molecular weight 534.43 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. Zhao XN, Bai ZZ, Li CH, Sheng CL, Li HY. The NK-1R Antagonist Aprepitant Prevents LPS-Induced Oxidative Stress and Inflammation in RAW264.7 Macrophages. Drug Des Devel Ther. 2020 May 20;14:1943-1952. doi: 10.2147/DDDT.S244099. PMID: 32546961; PMCID: PMC7246327. 2. Wang X, Douglas SD, Song L, Wang YJ, Ho WZ. Neurokinin-1 receptor antagonist (aprepitant) suppresses HIV-1 infection of microglia/macrophages. J Neuroimmune Pharmacol. 2008 Dec;3(4):257-64. doi: 10.1007/s11481-008-9117-3. Epub 2008 Jul 25. PMID: 18654860; PMCID: PMC2675876. 3. Wu H, Cheng X, Huang F, Shao G, Meng Y, Wang L, Wang T, Jia X, Yang T, Wang X, Fu C. Aprepitant Sensitizes Acute Myeloid Leukemia Cells to the Cytotoxic Effects of Cytosine Arabinoside in vitro and in vivo. Drug Des Devel Ther. 2020 Jun 18;14:2413-2422. doi: 10.2147/DDDT.S244648. PMID: 32606608; PMCID: PMC7308242. 4. Martinez AN, Burmeister AR, Ramesh G, Doyle-Meyers L, Marriott I, Philipp MT. Aprepitant limits in vivo neuroinflammatory responses in a rhesus model of Lyme neuroborreliosis. J Neuroinflammation. 2017 Feb 15;14(1):37. doi: 10.1186/s12974-017-0813-x. PMID: 28202084; PMCID: PMC5312540. |
| In vitro protocol: | 1. Zhao XN, Bai ZZ, Li CH, Sheng CL, Li HY. The NK-1R Antagonist Aprepitant Prevents LPS-Induced Oxidative Stress and Inflammation in RAW264.7 Macrophages. Drug Des Devel Ther. 2020 May 20;14:1943-1952. doi: 10.2147/DDDT.S244099. PMID: 32546961; PMCID: PMC7246327. 2. Wang X, Douglas SD, Song L, Wang YJ, Ho WZ. Neurokinin-1 receptor antagonist (aprepitant) suppresses HIV-1 infection of microglia/macrophages. J Neuroimmune Pharmacol. 2008 Dec;3(4):257-64. doi: 10.1007/s11481-008-9117-3. Epub 2008 Jul 25. PMID: 18654860; PMCID: PMC2675876. |
| In vivo protocol: | 1. Wu H, Cheng X, Huang F, Shao G, Meng Y, Wang L, Wang T, Jia X, Yang T, Wang X, Fu C. Aprepitant Sensitizes Acute Myeloid Leukemia Cells to the Cytotoxic Effects of Cytosine Arabinoside in vitro and in vivo. Drug Des Devel Ther. 2020 Jun 18;14:2413-2422. doi: 10.2147/DDDT.S244648. PMID: 32606608; PMCID: PMC7308242. 2. Martinez AN, Burmeister AR, Ramesh G, Doyle-Meyers L, Marriott I, Philipp MT. Aprepitant limits in vivo neuroinflammatory responses in a rhesus model of Lyme neuroborreliosis. J Neuroinflammation. 2017 Feb 15;14(1):37. doi: 10.1186/s12974-017-0813-x. PMID: 28202084; PMCID: PMC5312540. |
1: Aapro MS, Schmoll HJ, Jahn F, Carides AD, Webb RT. Review of the efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in a range of tumor types. Cancer Treat Rev. 2013 Feb;39(1):113-7. doi: 10.1016/j.ctrv.2012.09.002. Epub 2012 Oct 11. Review. PubMed PMID: 23062719.
2: Furukawa N, Kawaguchi R, Kobayashi H. Use of high-dose cisplatin with aprepitant in an outpatient setting. Eur J Cancer Care (Engl). 2012 Jul;21(4):436-41. doi: 10.1111/j.1365-2354.2011.01284.x. Epub 2011 Aug 25. Review. PubMed PMID: 21883567.
3: Hargreaves R, Ferreira JC, Hughes D, Brands J, Hale J, Mattson B, Mills S. Development of aprepitant, the first neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Ann N Y Acad Sci. 2011 Mar;1222:40-8. doi: 10.1111/j.1749-6632.2011.05961.x. Review. PubMed PMID: 21434941.
4: Ruhlmann CH, Herrstedt J. Safety evaluation of aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Expert Opin Drug Saf. 2011 May;10(3):449-62. doi: 10.1517/14740338.2011.563235. Epub 2011 Mar 21. Review. PubMed PMID: 21417835.
5: Kast RE. Glioblastoma: synergy of growth promotion between CCL5 and NK-1R can be thwarted by blocking CCL5 with miraviroc, an FDA approved anti-HIV drug and blocking NK-1R with aprepitant, an FDA approved anti-nausea drug. J Clin Pharm Ther. 2010 Dec;35(6):657-63. doi: 10.1111/j.1365-2710.2009.01148.x. Review. PubMed PMID: 21054456.
6: Aapro MS, Walko CM. Aprepitant: drug-drug interactions in perspective. Ann Oncol. 2010 Dec;21(12):2316-23. doi: 10.1093/annonc/mdq149. Epub 2010 May 20. Review. PubMed PMID: 20488873.
7: Sankhala KK, Pandya DM, Sarantopoulos J, Soefje SA, Giles FJ, Chawla SP. Prevention of chemotherapy induced nausea and vomiting: a focus on aprepitant. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1607-14. doi: 10.1517/17425250903451675. Review. PubMed PMID: 19929449.
8: Curran MP, Robinson DM. Aprepitant: a review of its use in the prevention of nausea and vomiting. Drugs. 2009;69(13):1853-78. doi: 10.2165/11203680-000000000-00000. Review. PubMed PMID: 19719336.
9: Sarcev T, Secen N, Zaric B, Milovancev A. Aprepitant--where do we stand in the control of chemotherapy-induced nausea and vomiting? J BUON. 2008 Jul-Sep;13(3):333-9. Review. PubMed PMID: 18979546.
10: Olver I, Shelukar S, Thompson KC. Nanomedicines in the treatment of emesis during chemotherapy: focus on aprepitant. Int J Nanomedicine. 2007;2(1):13-8. Review. PubMed PMID: 17722507; PubMed Central PMCID: PMC2673828.
