UK-5099（AbMole，M7455）是一種線粒體丙酮酸載體（MPC）抑制劑，通過阻斷丙酮酸進(jìn)入線粒體并抑制細(xì)胞有氧代謝，從而影響細(xì)胞的能量代謝途徑。UK-5099具有抑制腫瘤生長(zhǎng)的能力，在非小細(xì)胞肺癌（NSCLC）和乳腺癌等多種模型中均有活性。UK-5099在乳腺癌細(xì)胞（4T1）中以10 μM濃度處理24小時(shí)后顯著降低細(xì)胞的氧消耗率（OCR）和細(xì)胞外酸化率（ECAR），并誘導(dǎo)培養(yǎng)基pH下降，證實(shí)其對(duì)丙酮酸代謝的干擾[1]。同樣在10 μM的劑量下，UK-5099（CAS No.：56396-35-1）在宮頸癌細(xì)胞中增加了糖酵解活性（表現(xiàn)為葡萄糖消耗和乳酸釋放增加）[2]，其機(jī)制是UK-5099通過抑制線粒體丙酮酸轉(zhuǎn)運(yùn)，迫使細(xì)胞轉(zhuǎn)向糖酵解，導(dǎo)致乳酸積累和微環(huán)境酸化。UK-5099在BALB/c小鼠（乳腺癌4T1模型）中以每日腹腔注射3 mg/kg，共注射4天的實(shí)驗(yàn)方案有效降低了腫瘤pH（通過CEST-MRI檢測(cè)），證實(shí)其對(duì)腫瘤微環(huán)境的調(diào)控[2]。此外，UK-5099（PF-1005023）還被發(fā)現(xiàn)具有抗弓形蟲（Toxoplasma gondii）活性。
 
范例詳解
FASEB J. 2025 Jan 31;39(2):e70354.
AbMole的UK-5099（PF-1005023，AbMole，M7455）被科研人員用于處理間充質(zhì)干細(xì)胞（MSCs）以探究其在拉伸條件下，代謝系統(tǒng)的變化，結(jié)果顯示UK-5099有效抑制了拉伸條件下MSCs中的ATP產(chǎn)生。 
 
參考文獻(xiàn)及鳴謝
[1] Buyse, C.; Mignion, L.; Joudiou, N.; et al. Sensitive simultaneous measurements of oxygenation and extracellular pH by EPR using a stable monophosphonated trityl radical and lithium phthalocyanine. Free radical biology & medicine 2024, 213, 11-18.
[2] Buyse, C.; Joudiou, N.; Corbet, C.; et al. Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI. Cancers 2021, 13 (17).
[3] Liu, Y.; Yang, Z.; Na, J.; et al. In vitro stretch modulates mitochondrial dynamics and energy metabolism to induce smooth muscle differentiation in mesenchymal stem cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2025, 39 (2), e70354.