5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists), 5-HT2C receptor antagonists(Serotonin 2c (5-HT2c) receptor antagonists), D2 receptor antagonists(Dopamine D2 receptor antagonists)

+ [1]

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Schizophrenia

Originator Organization

SK Biopharmaceuticals Co., Ltd.

Active Organization-

Inactive Organization

SK Biopharmaceuticals Co., Ltd.

License Organization-

Drug Highest PhaseDiscontinuedPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC21H23FN2O3

InChIKeyFRKHSTMEWWIUQD-UHFFFAOYSA-N

CAS Registry666859-31-0

View All Structures (2)

100 Clinical Results associated with YKP-1358

100 Translational Medicine associated with YKP-1358

100 Patents (Medical) associated with YKP-1358

Literatures (Medical) associated with YKP-1358

01 Oct 2011·PsychopharmacologyQ3 · MEDICINE

The use of healthy volunteers instead of patients to inform drug dosing studies: a [11C]raclopride PET study

Q3 · MEDICINE

Article

Author: Lee, Jae Sung ; Kapur, Shitij ; Shin, Sang-Goo ; Kwon, Jun Soo ; Kim, Bo-Hyung ; Kim, Su Jin ; Howes, Oliver D. ; Yu, Kyung-Sang ; Turkheimer, Federico E. ; Kim, Euitae ; Kim, Yong Gil ; Jang, In-Jin ; Park, Jung Shin ; Jeong, Jae Min

RATIONALEReceptor occupancy study has been performed to evaluate pharmacokinetic profiles in new antipsychotic drug development. While these findings highlight the value of positron emission tomography (PET) for dose-finding study, what is unclear is if it is necessary to conduct these studies in patients with schizophrenia or whether studies in healthy volunteers are adequate.OBJECTIVESTo determine if it is necessary to conduct dopamine receptor occupancy studies in patients with schizophrenia or whether studies in healthy volunteers are adequate for dose-finding study, we compared the concentration-occupancy relationship in terms of EC(50) between patients and healthy volunteers.METHODSTen healthy volunteers and eight patients with schizophrenia participated in the study. We measured dopamine receptor occupancy using [(11)C]raclopride PET and plasma concentration of YKP1358, a novel antipsychotic drug under clinical development, at a number of time points after the administration of YKP1358. Pharmacokinetic data including area under the plasma concentration versus time curve, elimination half-life, maximum observed plasma concentration, and the time to reach the maximum observed plasma concentration were obtained. We explored the relationship between plasma concentration and dopamine D(2) receptor occupancy using E (max) model and calculated EC(50).RESULTSThe elimination half-life was longer in healthy volunteers than in patients. Other pharmacokinetic parameters were not significantly different between two groups. The EC(50) was 7.6 ng/ml (95% confidence interval (CI) 6.2-9.0) in healthy volunteers and 8.6 (95% CI 7.4-9.9) in patients.CONCLUSIONSThe antipsychotic concentration-occupancy relationship in patients can be estimated from the EC(50) data of healthy volunteers.

01 Aug 2011·Journal of Cerebral Blood Flow & Metabolism

Calculating Occupancy when One does not have Baseline: A Comparison of Different Options

Article

Author: Shin, Sang-Goo ; Howes, Oliver D ; Kwon, Jun Soo ; Jeong, Jae Min ; Kim, Euitae ; Kapur, Shitij ; Lee, Jae Sung ; Jang, In-Jin ; Yu, Kyung-Sang

Dopamine D2 receptor occupancy of antipsychotic drugs is calculated relative to the subject's D2 receptor binding potential (BP) in the drug-free state (baseline BP). Because baseline BP is seldom known in patients with schizophrenia, population means from unrelated control samples are often used to estimate it. However, this is likely to introduce bias and error into the occupancy measure. There is thus a need for a method to reliably estimate baseline BP for patient populations in whom it may be impractical or unethical to get baseline measurements. It has been previously found that the relationship between plasma concentration and dopamine receptor occupancy by antipsychotic drugs follows a sigmoid Emax model. Based on this, we developed a method for calculating dopamine D2 receptor occupancy by antipsychotic drugs using an inhibitory Emax model ( Imax method) that estimates individual baseline BPs. To validate this, we compared the result from the Imax method with actual occupancy and estimated occupancy calculated from the average baseline BP (substitution method). The data for validation were obtained from two different receptor occupancy studies with the antipsychotic medications YKP1358 and aripiprazole. We estimated the reliability between the true measured occupancy and the predicted occupancy using the intraclass correlation coefficient (ICC), and the variability of occupancy was also compared between the Imax and substitution methods. In YKP1358 study, all the ICCs of the Imax method were above 0.8, but those of the substitution method showed values lower than 0.8. In aripiprazole study, the ICCs of the Imax method were higher than those of the substitution method, but all the ICCs showed higher values than 0.8. The variability of Imax method was significantly smaller than that of substitution method in both studies. The Imax method shows better reliability and less variability than the substitution method. The Imax method can be applied for receptor occupancy study, and bring more reliability and accuracy to the occupancy study in patients with schizophrenia.

01 Jan 2009·The Korean Journal of Physiology and PharmacologyQ4 · MEDICINE

YKP1447, A Novel Potential Atypical Antipsychotic Agent

Q4 · MEDICINE

Article

Author: Kim, Yong Gil ; Kwak, Byong Sung ; Heo, Joon ; Dong, Seon Min ; Ji, Mi Kyung ; Cho, Jeong Woo

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-HT(2A), Ki=0.61 nM, 5-HT(2C), Ki=20.7 nM) and dopamine (D(2), Ki=45.9 nM, D(3), Ki=42.1 nM) receptors with over 10~100-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing (ED(50)=0.93 mg/kg) and DOI-induced head twitch (ED(50)=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine (ED(50)=0.54 mg/kg) and the avoidance response (ED(50)=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose (ED(50)=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

100 Deals associated with YKP-1358

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KEGG	Wiki	ATC	Drug Bank
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Indication	Highest Phase	Country/Location	Organization	Date
Schizophrenia	Preclinical	South Korea	SK Biopharmaceuticals Co., Ltd.	-

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