ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1645033
Discovery of a Selective Dual-specificity Tyrosine Phosphorylation-regulated Kinase 1B Inhibitor with Antiadipogenic and Anti-diabetic Activities
Provisionally accepted
Sein Kang1
Yoon-Ju Na1Kyoung Jin Choi1Won Hoon Jung1Areum Park1Jeonghui Im1Sung Bum Park1Byumseok Koh1Joo-Youn Lee1Kwang-Lae Hoe2Heung Jae Kim3Sang Joon Shin4*Hyuk Lee1*
Ki Young Kim1*- 1Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea
- 2Chungnam National University, Yuseong-gu, Republic of Korea
- 3TheraSid Bioscience Co Ltd, Seongnam-si, Republic of Korea
- 4Yonsei University College of Medicine, Seodaemun-gu, Republic of Korea
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Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) is implicated in metabolic diseases, with recent reports linking its high expression to adipocyte differentiation and metabolic disorders. This study investigated the anti-adipogenic and anti-diabetic effects of a novel selective DYRK1B inhibitor, (N-( 4-(3-(4-methoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)acetamide (KS-40070). We utilized 3T3-L1 cells, adipose-derived mesenchymal stem cells (ADMSC), and diet-induced obesity (DIO) mice to evaluate KS-40070's efficacy. Treatment with KS-40070 dosedependently inhibited 3T3-L1 preadipocyte differentiation, reducing key adipogenic transcription factors like PPARγ and C/EBPα, along with related proteins. KS-40070 suppressed lipid accumulation by decreasing Akt-FOXO1A signaling and GSK3β expression. Crucially, these effects were abolished in DYRK1B knock-down cells, confirming DYRK1B's role. In DIO mice, KS-40070 suppressed body weight gain, food consumption, serum lipid levels, and adipose tissue mass. It also improved insulin resistance and glucose intolerance. These findings suggest that inhibiting DYRK1B with agents like KS-40070 presents a promising therapeutic strategy for obesity and type 2 diabetes.
Keywords: dyrk1B, Adipogenesis, Obesity, type 2 diabetes, FOXO1A
Received: 11 Jun 2025; Accepted: 11 Jul 2025.
Copyright: © 2025 Kang, Na, Choi, Jung, Park, Im, Park, Koh, Lee, Hoe, Kim, Shin, Lee and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Sang Joon Shin, Yonsei University College of Medicine, Seodaemun-gu, Republic of Korea
Hyuk Lee, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea
Ki Young Kim, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea
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