ACS Chemical Biology Cover featuring TOYABURGINE

TOYABURGINE: Breakthrough in Anticancer Drug Discovery

April 18, 2025

Our groundbreaking research graces the cover of ACS Chemical Biology! TOYABURGINE, a highly potent anticancer agent, is born from a dynamic collaboration between the University of Toyama and the University of Würzburg. Its name, blending “Toya” and “Burg,” celebrates our global partnership and shared vision for transformative cancer therapies.

Led by Suresh Awale, this discovery advances natural drug development. Explore the science behind this milestone!

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Natural Drug Discovery Lab

Our laboratory focuses on discovering natural anticancer agents that target cancer cells' tolerance to nutrient starvation within the tumor microenvironment. Cancer cells typically proliferate rapidly and uncontrollably, leading to nutrient- and oxygen-deficient conditions due to poorly organized tumor vasculature. In hypovascular tumors, such as pancreatic cancer, cells adapt to these harsh conditions by modulating energy metabolism—a characteristic known as austerity.
Identifying natural compounds that disrupt this austerity is a central research objective. To this end, we pursue the following research areas:
  1. Antiausterity-Based Screening
    We evaluate traditional medicinal plants from various origins (e.g., Kampo medicines, Ayurvedic herbs) for antiausterity activity using human pancreatic cancer cell lines, including PANC-1, MIA PaCa-2, KLM-1, NOR-P1, Capan-1, and PSN-1.
  2. Discovery of Antiausterity Agents
    Using bioassay-guided fractionation and advanced chromatographic and spectroscopic techniques (e.g., NMR, MS, UV, IR, CD), we isolate, purify, and identify antiausterity compounds from natural sources. Promising candidates are assessed for in vivo antitumor efficacy in pancreatic cancer mouse models.
  3. Structure-Activity Relationship and Mechanistic Studies
    We investigate the structure-activity relationships (SAR) of active compounds and elucidate their molecular mechanisms, focusing on cancer cell survival pathways such as PI3K/AKT/mTOR and autophagy.
  4. Metabolic Impact Analysis
    Using FT-NMR and FT-MS, we analyze the effects of antiausterity agents on cancer cell metabolism to gain insights into their mechanisms under nutrient-deprived conditions.
Arctigenin: A Promising Antiausterity Agent in the Fight Against Pancreatic Cancer. Arctigenin, a potent natural anticancer compound identified through our antiausterity strategy, has shown remarkable activity against human pancreatic cancer in preclinical models. By targeting cancer cells’ ability to survive nutrient-starved conditions in the tumor microenvironment, arctigenin offers a novel approach to tackling aggressive cancers like pancreatic cancer. Excitingly, arctigenin (as GBS-01) has demonstrated a favorable safety profile and encouraging clinical responses in a Phase I clinical trial for patients with gemcitabine-refractory advanced pancreatic cancer, paving the way for further exploration in ongoing research.

天然薬物開発研究室

私たちの研究室では、腫瘍微小環境におけるがん細胞の栄養飢餓耐性を標的とした天然抗がん物質の探索を主要な研究テーマとしています。がん細胞は一般に無秩序かつ急速に増殖し、その結果、脆弱で不規則な腫瘍血管が形成されることで、栄養や酸素が不足した環境に曝されます。特に膵臓がんのような乏血管性腫瘍では、がん細胞はエネルギー代謝を調節することで、低栄養・低酸素といった過酷な環境に対する耐性（austerity）を獲得しています。
したがって、栄養飢餓耐性を解除する天然抗がん化合物の探索は、私たちの重要な研究目標の一つです。この目標を達成するため、以下の研究課題に積極的に取り組んでいます。

1. 抗がん活性のスクリーニング
ヒト膵臓がん細胞株（例：PANC-1、MIA PaCa-2、KLM-1、NOR-P1、Capan-1、PSN-1など）を用いて、がん細胞の栄養飢餓耐性を標的とした（antiausterity strategy）各地の伝統生薬（漢方薬、アーユルヴェーダ薬など）の抗がん活性を評価します。

2. 活性物質の探索と同定
抗がん活性を指標に、最先端のクロマトグラフィーおよび分光分析技術（NMR、MS、UV、IR、CDなど）を活用し、天然薬物資源から栄養飢餓耐性を解除する活性物質（antiausterity agent）を分離・精製・同定します。有望な候補物質については、ヒト膵臓がんのマウスモデルを用いて、in vivoでの抗腫瘍効果を評価します。

3. 構造活性相関および作用機序の解明
活性天然化合物の構造活性相関（SAR）研究を通じて、栄養飢餓耐性を解除する分子メカニズムを解明します。

4. 代謝解析
FT-NMRおよびFT-MSを用いて、活性物質（antiausterity agent）が膵臓がん細胞の代謝に及ぼす影響を詳細に解析します。
Journal Cover

自然物医薬品発見の画期的な進展：膵臓がんに対する「Journal of Natural Products」表紙に掲載

私たちは、ニカイオイデシンCに関する先駆的な研究が、権威ある「Journal of Natural Products」（第86巻、第6号）の表紙を飾ったことを心から喜ばしく思います。この発見は、富山大学のスレス・アワレ准教授が主導し、Boesenbergia pandurataから派生した強力な自然物を明らかにし、膵臓がんとの戦いを再定義する可能性を秘めています。

研究を読む

Empowering Health Through Natural Products Drug Discovery

What truly drives me is the belief that nature's ancient wisdom, combined with cutting-edge science, holds the key to revolutionary breakthroughs in global health. I'm on a mission to bridge traditional healing with modern chemistry and biology, tirelessly exploring possibilities where others see limits, and turning natural drug research into transformative discoveries.

— Suresh Awale

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