Netupitant  (Synonyms: CID 6451149)

Netupitant (CID-6451149) is a highly potent, selective and orally active neurokinin-1 (NK₁) receptor antagonist with a K_i of 0.95 nM for hNK₁ in CHO cells. Netupitant has antiemetic affect^[1][2][3].

Netupitant (CID-6451149) binds with high affinity the human NK₁ receptor (pK_i=9.0) with more than 1000 fold selectivity over the NK₂ and NK₃ (pK_i=5.8 for both sites)^[2].
Netupitant (1, 10, 100 nM) concentration-dependently antagonizes the stimulatory effects of substance P (SP) showing insurmountable antagonism (pK_B=8.87) in CHO NK₁ cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Netupitant (CID-6451149; 1-10 mg/kg; ip) dose-dependently inhibits SP-elicited the typical scratching, biting and licking response in mice. In gerbils, foot tapping behavior evoked by the intracerebroventricular injection of a NK₁ agonist is dose-dependently counteracted by Netupitant given intraperitoneally (ID₅₀ 1.5mg/kg) or orally (ID₅₀ 0.5mg/kg)^[2].
Netupitant (0.1-3 mg/kg; i.v.) produces a concentration-dependent inhibition (mean pK_B=9.24) of the responses to SP-methylester (SP-OMe) in the detrusor muscle. Netupitant decreases the frequency of reflex bladder contractions^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

578.59

C₃₀H₃₂F₆N₄O

290297-26-6

Solid

White to off-white

CN1CCN(C2=CC(C3=C(C)C=CC=C3)=C(N(C)C(C(C4=CC(C(F)(F)F)=CC(C(F)(F)F)=C4)(C)C)=O)C=N2)CC1

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Hoffmann T, et al. Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1362-5.  [Content Brief]

  [2]. Rizzi A, et al. In vitro and in vivo pharmacological characterization of the novel NK1 receptor selective antagonist Netupitant. Peptides. 2012 Sep;37(1):86-97.  [Content Brief]

  [3]. Stefano Palea, et al. Netupitant, a Potent and Highly Selective NK1 Receptor Antagonist, Alleviates Acetic Acid-Induced Bladder Overactivity in Anesthetized Guinea-Pigs. Front Pharmacol. 2016 Aug 4;7:234.  [Content Brief]