Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 2, pp 363–369 | Cite as

Human microdosing and mice xenograft data of AGM-130 applied to estimate efficacious doses in patients

  • Wan-Su Park
  • Gab-jin Park
  • Seunghoon Han
  • Sooho Ban
  • Moon-Young Park
  • San-ho Kim
  • Seon-Myung Kim
  • Yong-Chul Kim
  • Hyung Sik Kim
  • Young G. Shin
  • Dong-Seok YimEmail author
Original Article



AGM-130 is a cyclin-dependent kinase inhibitor that exhibits dose-dependent efficacy in xenograft mouse models. During preclinical pharmacokinetic (PK) studies, mice and rats showed comparable PK parameters while dogs showed unusually high clearance (CL), which has made human PK prediction challenging. To address this discrepancy, we performed a human microdosing PK and developed a mouse PK/PD model in order to guide the first-in-human studies.


A microdose of AGM-130 was given via intravenous injection to healthy subjects. Efficacy data obtained using MCF-7 breast cancer cells implanted in mice was analyzed using pre-existing tumor growth inhibition models. We simulated a human PK/PD profile with the PK parameters obtained from the microdose study and the PD parameters estimated from the xenograft PK/PD model.


The human CL of AGM-130 was 3.08 L/h/kg, which was comparable to CL in mice and rats. The time-courses of tumor growth in xenograft model was well described by a preexisting model. Our simulation indicated that the human doses needed for 50 and 90% inhibition of tumor growth were about 100 and 400 mg, respectively.


This is the first report of using microdose PK and xenograft PK/PD model to predict efficacious doses before the first-in-human trial in cancer patients. In addition, this work highlights the importance of integration of all of information in PK/PD analysis and illustrates how modeling and simulation can be used to add value in the early stages of drug development.


Human microdose Tumor growth inhibition AGM-130 Cyclin-dependent kinase Cancer 



This research was supported by Anygen Co., Ltd.

Compliance with ethical standards

Conflict of interest

Sooho Ban, Moon-Young Park, San-ho Kim, Seon-Myung Kim and Yong-Chul Kim are employed by Anygen Co., Ltd. The other authors have no conflicts of interest to declare.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Wan-Su Park
    • 1
    • 2
  • Gab-jin Park
    • 1
    • 2
  • Seunghoon Han
    • 1
    • 2
  • Sooho Ban
    • 3
  • Moon-Young Park
    • 3
  • San-ho Kim
    • 3
  • Seon-Myung Kim
    • 3
  • Yong-Chul Kim
    • 3
    • 4
  • Hyung Sik Kim
    • 5
  • Young G. Shin
    • 6
  • Dong-Seok Yim
    • 1
    • 2
    Email author
  1. 1.Department of Clinical Pharmacology and TherapeuticsSeoul St. Mary’s HospitalSeoulKorea
  2. 2.PIPET (Pharmacometrics Institute for Practical Education and Training), College of MedicineThe Catholic University of KoreaSeoulKorea
  3. 3.Division of Drug DiscoveryAnygen Co., LtdGwangjuKorea
  4. 4.School of Life SciencesGwangju Institute of Science and TechnologyGwangjuKorea
  5. 5.School of PharmacySungkyunkwan UniversitySuwonKorea
  6. 6.College of PharmacyChungnam National UniversityDaejeonKorea

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