Netupitant_product_DataBase

Bioactivity

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

Invitro

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

In Vivo

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 pKB=9.24) of the responses to SP-methylester (SP-OMe) in the detrusor muscle. Netupitant decreases the frequency of reflex bladder contractions[3].

Name

Netupitant

CAS

290297-26-6

Formula

C30H32F6N4O

Molar Mass

578.59

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[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. [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. [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.

PeptideDB

Netupitant

CAS: 290297-26-6 F: C30H32F6N4O W: 578.59