第８回日中薬理学・臨床薬理学
ジョイントミーティング
The 8th Japan-China Joint Meetingof Basic and Clinical Pharmacology

Wed., March 10, 2021 Room A 13:30－17:00
札幌コンベンションセンター
SAPPORO CONVENTION CENTER

Welcome Message
On behalf of the Japanese Pharmacological Society and the Organizing Committee ofthe 94th Annual Meeting of the Japanese Pharmacological Society, we cordially invite
you to attend the 8th Japan-China Joint Meeting of Basic and Clinical Pharmacology.
This joint meeting will be held as the Japan-China Joint Session of the 94th Annual
Meeting of the Japanese Pharmacological Society held in Sapporo on March 10, 2021.
The last Japan-China Joint Meeting of Basic and Clinical Pharmacology was organizedby the Chinese Pharmacological Society, and it was held in Kunming, Yunnan Province,
China, at August 4-5, 2019. The Japan-China Joint Meeting has picked up the mostadvanced topics on pharmacology and contributes great progress of pharmacologicalsciences in both countries. It should be noted that young pharmacologists and students
in both countries could get to know each other through the Joint Meeting, and had grown
up to leading the pharmacological sciences in both countries.
This Joint Meeting is the important basis of continued collaboration and partnership on
basic and clinical pharmacology between Japan and China. This Joint Meeting isplanned to provide excellent opportunities to discuss among the scientists forpharmacological research, and to foster active pharmacologists responsible forinternational collaboration in the future. This meeting is sponsored by several Japanesefoundations. The organizing committee appreciates their great contributions for giving us
this opportunity for organizing the wonderful lectures on basic and clinical pharmacology.
It is worth noting that this will be the first Joint Meeting to be held online due to theepidemic of COVID-19 infections in the world.

Kazuhiko Yanai, MD., Ph.D.

Mitsuhiro Yoshioka, M.D., Ph.DPresident, the Japanese Pharmacological Society
Professor, Department of Pharmacology, Tohoku
University Graduate School of Medicine

President, The 94th Annual Meeting of theJapanese Pharmacological Society
Dean, Faculty of Medicine, Hokkaido University
Professor, Department of Neuropharmacology,
Faculty of Medicine, Hokkaido University

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Dear Colleagues,
As the 8th Japan-China Joint Meeting of Basic and ClinicalPharmacology is coming, on behalf of Chinese
Pharmacological Society, I wish to extend our warm greetingsand sincere invitations to all our colleagues on pharmacologicalresearch in both Japan and China.
With great endeavors and struggles, we bid farewell to theextraordinary 2020, and embraced the beautiful spring of 2021.
Looking back at 2020, The sudden pandemic of COVID-19 hit
the world with a great threat to the people’s life and health. People around the world went
all out to fight the pandemic, and have achieved great progress. During this process, we
deeply realized the important role of science and technology, and also the essential
significance of innovation and rapid new drug R&D in prevention and control of thepandemic.
The Japan-China Joint Meeting of Basic and Clinical Pharmacology co-organized by theChinese Pharmacological Society (CNPHARS), the Japanese Pharmacological Society(JPS) and the Japanese Society of Clinical Pharmacology and Therapeutics (JSCPT) has
been successfully held for 7 times, playing an important role in promoting the academic
exchanges and cooperation, improving the mutual understanding and friendship, andboosting the development of pharmacology in our two countries.
The topics of this joint meeting are Molecular Pharmacology Study and Early Clinical Trials
related pharmacological research which are all the current hot research areas in basic
pharmacology and clinical pharmacology. Due to COVID-19, this meeting will be a virtual
one. JPS and JSCPT are making thoughtful and meticulous preparations for this event.
We believe that the meeting will be a complete success as always.
Dear colleagues, welcome to attend this meeting, take part in the scientificcommunications, and make new contributions to the development of pharmacology.

Yongxiang Zhang
The President of Chinese Pharmacological Society

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ChairJianguo ChenTongji Med. Coll., Huazhong Univ. Sci. Technol.
Yoshikatsu Kanai
Grad. Sch. Med., Osaka Univ.
Wei WeiInst. Clin. Pharmacol., Anhui Med. Univ.
Ichiro Ieiri
Grad. Sch. Pharmaceut. Sci. Kyushu Univ.

Speaker
3-S32-1

Networks of organelle function in cardiovascular diseases
Yong Zhang
Dept. Pharmacol., Coll. Pharm., Harbin Med. Univ.

3-S32-2

Redox regulation of mitochondrial quality as a therapeutic target ofcardiac senescence
Motohiro Nishida
Grad. Sch. Pharm. Sci., Kyushu Univ. / NIPS

3-S32-3

Accelerating development of proton pump inhibitors: a mechanismbased PK/PD model to optimize dose design with ilaprazole as acase drug
Hongyun Wang
Clin. Pharm. Res. Cent., Peking Union Med. Coll. Hosp.

3-S32-4

Development of endogenous biomarkers to assess drugtransporter-mediated drug-drug interactions in drug development
Hiroyuki KusuharaGrad. Sch. Pharm. Sci., Univ. Tokyo* The presentation order will be changed as follows: 1. Hongyun Wang(3-S32-3),
2. Hiroyuki Kusuhara(3-S32-4), 3. Yong Zhang(3-S32-1), 4. Motohiro Nishida(3-S32-2)

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Networks of organelle function in cardiovascular diseases
Yong Zhang

Dept. Pharmacol., Coll. Pharm., Harbin Med. Univ.
Cardiovascular diseases (CVDs) are the leader global cause of death. Cell organelles
determines cells fate in CVDs. Here we studied the regulatory effects of non-coding RNAs
on function and crosstalk among cell organelles especially in endoplasmic reticulum (ER)and mitochondria in different CVDs. In mitochondria, we found mitomiR-4485-3p andlncRNA MIAT impaired myocardial infarction (MI) by inducing cardiomyocytes apoptosis.
MitomiR-4485-3p released to cytosol in response to injury in MI, which targeted PPARαand induced dysregulation of mitochondrial energy metabolism and apoptosis incardiomyocytes. In addition, lncRNA MIAT induces cardiomyocytes apoptosis and impairs
cardiac contractile function by acting on mitochondrial translocator protein TSPO in MI. InER, we identified lncRNA ZFAS1 as a regulator of calcium homeostasis in a mouse modelof pressure-overload HF. We found that circulating level of lncRNA ZFAS1 wassignificantly lower in MI than in non-MI patients. Then we revealed lncRNA-ZFAS1 as anatural inhibitor of SERCA2a by binding to SERCA2a protein. Abnormally increased
ZFAS1 in MI significantly impaired cardiac function. Most prominently, we identified aregion of high degree conservation across man and mouse species named functionalsequence domain of ZFAS1, which is much shorter and responsible for its deleterious
effects. Our study identified functional non-coding RNAs as network hub of organelles inCVDs, which provides potential therapeutic agents for ameliorating cardiac dysfunction.

3-S32-2

Redox regulation of mitochondrial quality as a therapeutic targetof cardiac senescence
Motohiro Nishida

Grad. Sch. Pharm. Sci., Kyushu Univ. / NIPS
Mitochondria are dynamic organelles that continuously undergo fission and fusion, which
are necessary for maintaining bioenergetic homeostasis and robustness in heart.
Mitochondrial fission and fusion cycle is precisely regulated by three GTP-binding proteins,
dynamin-related protein 1 (Drp1), mitofusins (Mfn1 and mfn2) and optic atrophy 1 (Opa1),
and these three G proteins have redox-sensitive cysteine (Cys) residues. Especially,
mitochondria predominantly show tubular form in adult cardiomyocytes and are reported
to be fragmented by the exposure to electrophilic chemical substances produced byhypoxic and hyperglycemic stress. We found that depolysulfidation of Cys624 on Drp1,
caused by endogenous or exogenous electrophiles, increased basal Drp1 GTPase activity
as well as cardiac vulnerability to hemodynamic load in mouse hearts. Reactive sulfide
species such as Cys persulfide produced through mitochondria-localized Cys tRNA
synthetase (CARS2) preferentially eliminate and metabolize electrophiles. Proteinpersulfide detection assay revealed that endogenous Drp1 protein possesses several Cys
persulfides in a CARS2) dependent manner, and exposure to environmental electrophiles
such as methylmercury (MeHg) reduced Drp1 persulfide levels. Supplementation of sulfur
to Cys-624 by exogenous treatment with NaHS completely abolished MeHg-induced sulfur
deprivation of Drp1 protein as well as exacerbation of myocardial injury induced bymechanical stress. These results strongly suggest that formation of Drp1 Cys624
polysulfidation negatively regulates electrophile-mediated mitochondrial hyperfission andcardiac stress resistance against environmental stresses.
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3-S32-3

Application of Clinical Pharmacology in Early Clinical Drug
Development: PK/PD studies of a new proton pump inhibitor
Hongyun Wang
Clin. Pharm. Res. Cent., Peking Union Med. Coll. Hosp.

Clinical pharmacology is critical in drug development. This presentation introduces thecurrent status of its application in China, and then presents a PK/PD model for protonpump inhibitor (PPI) drugs. This mechanism-based model is established using ilaprazole
as a case drug in which food effect and circadian rhythm are taken into account, and it
provides a potential strategy to accelerate the development of novel PPIs.

3-S32-4

Development of endogenous biomarkers to assess drugtransporter-mediated drug-drug interactions in drug
development
Hiroyuki KusuharaGrad. Sch. Pharm. Sci., Univ. Tokyo

Drug transporters act as determinant for the clearance of drugs from the blood circulationin the liver and kidney. Inhibition of such transporters by drugs causes accumulation of
their substrate drugs, and thereby increasing the risk of adverse reactions in combinationuse. In drug development, it is prerequisite to assess the inhibition potency of theinvestigation drugs against major drug transporters. Recently, endogenous biomarkers
have emerged to advance this risk assessment in the clinical stage. We identified someendogenous substrates in healthy volunteers using well characterized inhibitors andmetabolomic approach for the drug transporters such as OATP1B1/1B3, OAT1, OAT3 andOCT2, MATE1/2-K whose pharmacokinetic parameters, such as AUC and renal clearance(CLR), changed according to the degree of inhibition of drug transporters. Physiologicallybased pharmacokinetic (PBPK) models for the endogenous substrates have been also
constructed to explain the effect of inhibitors. PBPK-model based approach are highly
expected to extrapolate the biomarker data to the DDI. The endogenous biomarkers arehighly expected to improve predictability of the DDI in early phase of clinical stage of drug
development, and aids design of the strategy to de-risk of the DDI in the clinical settings.

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