| Description | Rolapitant (SCH619734) Hydrochloride is the hydrochloride salt form of rolapitant, an orally bioavailable, centrally-acting, selective, neurokinin 1 receptor (NK1-receptor) antagonist with potential antiemetic activity. Upon oral administration, rolapitant competitively binds to and blocks the activity of the NK1-receptor in the central nervous system, thereby inhibiting the binding of the endogenous ligand, substance P (SP). This may prevent both SP-induced emesis and chemotherapy-induced nausea and vomiting (CINV). The interaction of SP with the NK1-receptor plays a key role in the induction of nausea and vomiting caused by emetogenic cancer chemotherapy. Compared to other NK1-receptor antagonists, rolapitant has both a more rapid onset of action and a much longer half-life. |
| In vitro | Rolapitant对人类NK1受体具有高亲和力，Ki值为0.66 nM，且对人类NK2和NK3亚型的选择性超过1000倍。Rolapitant对人类、豚鼠、沙鼠和猴子的NK1受体具有较高亲和力，相较于大鼠、小鼠和兔子的NK1受体[1]。 |
| In vivo | Rolapitant 通过静脉注射和口服给药，在最小有效剂量（MED）0.1 mg/kg 下，可逆转NK1激动剂在沙鼠中引起的脚踏动作，持续时间达24小时。在急性和延迟呕吐模型中，Rolapitant 在0.1和1 mg/kg剂量下对雪貂均有效，这与其他NK1拮抗剂的临床数据一致。抗呕吐药的临床效果与雪貂呕吐模型中的效果高度相关，暗示Rolapitant是这一适应症的有力临床候选者[1]。 |
| Target activity | NK1:0.66 nM. (Ki) |
| Synonyms | 罗拉吡坦, SCH619734, 罗拉匹坦 |
| molecular weight | 500.48 |
| Molecular formula | C25H26F6N2O2 |
| CAS | 552292-08-7 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 55 mg/mL (109.89 mM), Sonication is recommended. |
| References | 1. Duffy RA, et al. Rolapitant (SCH 619734): a potent, selective and orally active neurokininNK1 receptor antagonist with centrally-mediated antiemetic effects inferrets. Pharmacol Biochem Behav. 2012 Jul;102(1):95-100. |