Aprepitant

• CAT Number: A000979
• CAS Number: 170729-80-3
• Molecular Formula: C₂₃H₂₁F₇N₄O₃
• Molecular Weight: 534.43
• Purity: ≥95%
• Target: Substance P/NK1 Receptor
• Solubility: >26.7mg/mL in DMSO
• Storage: -20°C
• InChI: 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
• InChIKey: ATALOFNDEOCMKK-OITMNORJSA-N
• SMILES: CC(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC2C(N(CCO2)CC3=NC(=O)NN3)C4=CC=C(C=C4)F

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.

Reference

1: Bailard N, Rebello E. Aprepitant and fosaprepitant decrease the effectiveness
of hormonal contraceptives. Br J Clin Pharmacol. 2017 Dec 19. doi:
10.1111/bcp.13472. [Epub ahead of print] PubMed PMID: 29266364.

2: Mehra N, Ganesan P, Ganesan TS, Veeriah S, Boopathy A, Radhakrishnan V,
Dhanushkodi M, Rajaraman S, Ganesharajah S, Sagar TG. Effectiveness of olanzapine
in patients who fail therapy with aprepitant while receiving highly emetogenic
chemotherapy. Med Oncol. 2017 Dec 16;35(1):12. doi: 10.1007/s12032-017-1074-3.
PubMed PMID: 29248965.

3: Zacharis CK, Vastardi E. Application of analytical quality by design
principles for the determination of alkyl p-toluenesulfonates impurities in
Aprepitant by HPLC. Validation using total-error concept. J Pharm Biomed Anal.
2017 Dec 7;150:152-161. doi: 10.1016/j.jpba.2017.12.009. [Epub ahead of print]
PubMed PMID: 29245084.

4: Lönndahl L, Holst M, Bradley M, Killasli H, Heilborn J, Hall MA, Theodorsson
E, Holmberg J, Nordlind K. Substance P Antagonist Aprepitant Shows no Additive
Effect Compared with Standardized Topical Treatment Alone in Patients with Atopic
Dermatitis. Acta Derm Venereol. 2017 Nov 28. doi: 10.2340/00015555-2852. [Epub
ahead of print] PubMed PMID: 29182791.

5: Maroñas-Jiménez L, Estrach T, Gallardo F, Pérez A, Andrés Borja H, Servitje O,
Pérez Gala S, Linares Barrio M, Jiménez Gallo D, Sanz-Bueno DJ, Lora D, Monsálvez
V, Ortiz-Romero PL. Aprepitant improves refractory pruritus in primary cutaneous
T-cell lymphomas: experience of the Spanish Working Group on Cutaneous Lymphomas.
Br J Dermatol. 2017 Nov 18. doi: 10.1111/bjd.16128. [Epub ahead of print] PubMed
PMID: 29150837.

6: Ioroi T, Furukawa J, Kume M, Hirata S, Utsubo Y, Mizuta N, Miyake H, Fujisawa
M, Hirai M. Phase II study of palonosetron, aprepitant and dexamethasone to
prevent nausea and vomiting induced by multiple-day emetogenic chemotherapy.
Support Care Cancer. 2017 Nov 16. doi: 10.1007/s00520-017-3967-2. [Epub ahead of
print] PubMed PMID: 29147855.

7: Pasricha PJ, Yates KP, Sarosiek I, McCallum RW, Abell TL, Koch KL, Nguyen LAB,
Snape WJ, Hasler WL, Clarke JO, Dhalla S, Stein EM, Lee LA, Miriel LA, Van Natta
ML, Grover M, Farrugia G, Tonascia J, Hamilton FA, Parkman HP; NIDDK
Gastroparesis Clinical Research Consortium (GpCRC). Aprepitant Has Mixed Effects
on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related
Disorders. Gastroenterology. 2018 Jan;154(1):65-76.e11. doi:
10.1053/j.gastro.2017.08.033. Epub 2017 Oct 28. PubMed PMID: 29111115; PubMed
Central PMCID: PMC5742047.

8: Zhang L, Lu S, Feng J, Dechaphunkul A, Chang J, Wang D, Chessari S, Lanzarotti
C, Jordan K, Aapro M. A Randomized Phase 3 Study Evaluating the Efficacy of
Single-dose NEPA, a Fixed Antiemetic Combination of Netupitant and Palonosetron,
Versus an Aprepitant Regimen for Prevention of Chemotherapy-induced Nausea and
Vomiting (CINV) in Patients Receiving Highly Emetogenic Chemotherapy (HEC). Ann
Oncol. 2017 Oct 28. doi: 10.1093/annonc/mdx698. [Epub ahead of print] PubMed
PMID: 29092012.

9: Bubalo JS, Herrington JD, Takemoto M, Willman P, Edwards MS, Williams C,
Fisher A, Palumbo A, Chen E, Blanke C, Lopez CD. Phase II open label pilot trial
of aprepitant and palonosetron for the prevention of chemotherapy-induced nausea
and vomiting (CINV) in patients receiving moderately emetogenic FOLFOX
chemotherapy for the treatment of colorectal cancer. Support Care Cancer. 2017
Oct 31. doi: 10.1007/s00520-017-3950-y. [Epub ahead of print] PubMed PMID:
29090385.

10: Morita M, Kishi S, Ookura M, Matsuda Y, Tai K, Yamauchi T, Ueda T. Efficacy
of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and anorexia. Curr
Probl Cancer. 2017 Nov – Dec;41(6):419-425. doi:
10.1016/j.currproblcancer.2017.09.001. Epub 2017 Sep 23. PubMed PMID: 29061362.