Rolapitant hydrochloride

SKU: orb1303843

Description

Rolapitant hydrochloride (CAS 858102-79-1) is a potent, selective, orally active NK1 receptor antagonist (Ki=0.66 nM) with long duration and no CYP3A4 interaction. It demonstrates central anti-emetic effects in ferret models, supporting research in chemotherapy-induced nausea and vomiting within neuropharmacology and oncology.

Research Area

Neuroscience, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 858102-79-1
• MW: 536.94
• Purity: 98.46%
• Formula: C₂₅H₂₇ClF₆N₂O₂
• SMILES: Cl.C[C@@H](OC[C@]1(CC[C@]2(CCC(=O)N2)CN1)c1ccccc1)c1cc(cc(c1)C(F)(F)F)C(F)(F)F
• Target: Neurokinin receptor
• Solubility: DMSO:50 mg/mL (93.12 mM)

Bioactivity

• Target IC50:
  NK1 (monkey):2.5 (Ki)|NK1 (mouse):60.4 (Ki)|NK1 (rat):78.6 (Ki)|NK1 (rabbit):31.7 (Ki)|NK1 (gerbil):0.13 (Ki)|NK1 (human):0.66 (Ki)|NK1 (guinea pig):0.72 (Ki)
• In Vivo:
  Rolapitant, administered orally (0.03-1 mg/kg) or intravenously (0.3-1 mg/kg) as a single dose, effectively mitigates the GR-73632-induced foot-tapping in Mongolian Gerbils and prevents acute emesis triggered by apomorphine and cisplatin in ferrets, with observations lasting up to 72 hours. In the Mongolian Gerbil model, the compound, when given orally, significantly reduces the foot-tapping response, achieving an ID90 at 0.3 mg/kg and maintaining inhibition for over 24 hours. Intravenous administration resulted in a complete cessation of foot-tapping at a dose of 1 mg/kg. In ferrets, rolapitant dose-dependently inhibits vomiting and retching induced by both emetic agents over a 72-hour period, illustrating its potential as an effective clinical antiemetic. This aligns with the ferret emesis model's predictive value for clinical antiemetic efficacy, endorsing rolapitant as a promising candidate for this purpose.
• In Vitro:
  In vitro studies indicate that rolapitant has a high affinity for the human NK1 receptor of 0.66 nM and high selectivity over the human NK2 and NK3 subtypes of >1000-fold, as well as preferential affinity for human, guinea pig, gerbil and monkey NK1 receptors over rat, mouse and rabbit . Rolapitant (1-1000 nM) inhibits the GR-73632 (an NK1 receptor agonist)-induced calcium efflux with a concentration-dependent and competitive manner in CHO cells expressing the human NK1 receptor .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

NK1, Neurokininreceptor, Neurokinin receptor, Rolapitant HCl, Rolapitant hydrochloride, Rolapitant Hydrochloride

Compound Identifiers

PubChem CID

71587824