細胞週期與DNA損傷 Cell cycle and DNA damage
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細胞週期 Cell cycle
在細胞週期 (cell cycle) 中是透過週期蛋白依賴性激酶或週期素依賴性激酶(cyclin-dependent
kinases, CDKs) 來調控細胞生長 (cell growth)、DNA 複製 (DNA replication) 與細胞分裂 (cell division) 的所有過程。在整個細胞週期中有幾個檢查站 (checkpoint)，為錯誤的訊息或是訊號把關，例如：DNA 損傷、紡錘體 (spindle) 形成不當等，確保細胞週期能夠持續運轉。當細胞週期運轉異常時，可能會造成細胞異常增殖與基因組的不穩定性，最終導致癌症細胞的產生。
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| 品名 | 分析内容 | 貨號 |
| Cell cycle assay kit | · Easy-to-use kit for flow cytometric analysis of cell cycle progression · Determine the percentage of cells in G0/G1, G2, or S phase | 10009349 |
| Senescence-Associated β-Galactosidase Staining Kit | · Enables visual detection of senescent cells using a chromogenic substrate | 602010 |
週期蛋白依賴性激酶 CDKs
CDKs 激酶與特定的細胞週期蛋白因子共同調控細胞週期中各個階段。當CDKs 激酶功能異常時則會引發癌症細胞的產生。不同的CDKs 激酶與其因子調控的階段如下：
Cdk4/cyclin D 和Cdk6/cyclin D：G1 phase
Cdk2/cyclin E：S phase 初期
Cdk1/cyclin A 和Cdk2/cyclin A：S phase
Cdk1/cyclin B：有絲分裂 (mitosis)
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| 貨號 | 品名 | 活性 |
| 21765 | Butyrolactone I | An ATP-competitive inhibitor of Cdk1 (IC50 = 20 μg/ml in PC-14 cells); induces dose-dependent G2/M arrest, inhibits DNA synthesis, and decreases Cdk1 protein expression in vitro |
| 18859 | Cdk1/2 Inhibitor III | A cell-permeable inhibitor of Cdk1/cyclin B and Cdk2/cyclin A (IC50s = 0.6 and 0.5 nM, respectively) |
| 17666 | LEE011 | Targets Cdk4/cyclin D1 and Cdk6/cyclin D3 at nanomolar concentrations; prevents CDK-mediated G1/S phase transition, arresting the cell cycle in the G1 phase, suppressing DNA synthesis, and inhibiting cancer cell growth |
| 21560 | LY2835219 | Orally bioavailable dual inhibitor of Cdk4 and Cdk6 (IC50s = 2 and 10 nM, respectively); induces G1 arrest |
| 13317 | NU 6102 | Inhibits Cdk1 and Cdk2 (IC50s = 9.5 and 5.4 nM, respectively); delays cell entry into mitosis |
| 21474 | PHA-848125 | An ATP-competitive inhibitor of Cdk2/cyclin A (IC50 = 45 nM); at least 3-fold less potent at Cdk1, -3, -4, -5, and -7 |
| 16273 | PD 0332991 (hydrochloride) | An orally active, selective inhibitor of Cdk4 (IC50 = 11 nM) and Cdk6 (IC50= 16 nM); induces G1 arrest |
| 15149 | Ro 3306 | A cell-permeable, reversible inhibitor of Cdk1; selective for Cdk1/cyclin B1 (Ki = 35 nM) over Cdk1/cyclin A (Ki = 110 nM); induces reversible cell cycle arrest at the G2/M phase border |
| 10009569 | (R)-Roscovitine | An inhibitor of Cdk2/cyclin E (IC50 = 0.1 μM); also inhibits Cdk7/cyclin H, Cdk5/p35, and cell division cycle (cdc)/cyclin B (IC50s = 0.49, 0.16, and 0.65 μM, respectively) |
DNA 損傷劑 DNA damaging agents
內源性的壓力來源 ：活性氧類 （ROS）、拓璞異構酵素抑制劑 （topoisomerase inhibitors）、DNA 烷化劑 （DNA alkylating）或交聯劑 crosslinking agents，以及核苷類似物 （nucleoside analogs）等皆有可能會造成DNA 損傷，進而影響細胞週期。 臨床上使用的化療藥物，是透過S phase 的活化來引發DNA 損傷，進而抑制癌症細胞DNA 的複
製，促進癌症細胞的老化與凋亡，抑制癌症細胞的生長。
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| DNA Topoisomerase Inhibitors | |
| DNA 單股或雙股螺旋的裂解可以透過抑制DNA topoisomerase 酵素活性完成 | |
| 貨號 | 品名 |
| 11694 | Camptothecin |
| 15007 | Doxorubicin (hydrochloride) |
| 12092 | Etoposide |
| 14180 | Irinotecan (hydrochloride hydrate) |
| 14129 | Topotecan (hydrochloride) |
| DNA Crosslinking Agents | |
| 含鉑 (platinum) 的DNA 交聯劑與DNA 或是DNA 蛋白交聯，干擾DNA 和RNA 的生成 | |
| 貨號 | 品名 |
| 13112 | Carboplatin |
| 13119 | Cisplatin |
| 29001 | Nedaplatin |
| 13106 | Oxaliplatin |
| DNA Alkylating Agents | |
| 烷基與DNA 鹼基對反應，誘導DNA 雙股螺旋鍵接的分裂，抑制細胞分裂，促進細胞死亡 | |
| 貨號 | 品名 |
| 23693 | Bendamustine (hydrochloride) |
| 19527 | 4-hydroperoxy Cyclophosphamide |
| 16665 | Melphalan |
| 11435 | Mitomycin C |
| 14163 | Temozolomide |
| Nucleoside Analogs | |
| 這些抗癌劑可以在復製過程中結合到 DNA 中，導致複製叉停滯和鏈終止。多種核苷類似物也抑制關鍵的細胞酶 | |
| 貨號 | 品名 |
| 16069 | Cytarabine |
| 14154 | Floxuridine |
| 14128 | Fludarabine |
| 14416 | 5-Fluorouracil |
| 11690 | Gemcitabine |
| 21366 | Trifluorothymidine |
DNA 損傷檢查站與修復 DNA Damage Checkpoints & Repair
DNA 損傷的檢測可以激活G1 期、S 期和G2/M 過渡期的細胞週期檢查點，以阻止細胞週期並進行DNA 修復。當DNA 複製壓力增加時，Ataxia-telangiectasia 和Rad3 相關蛋白/ 激酶 (ATR) 會被激活，使單股斷裂；而當Ataxia-telangiectasia mutated kinase (ATM) 活化時，則使雙股螺旋斷裂。ATR 和ATM 也會個別活化Chk1 和Chk2 激酶，進而調控下游的CDK/cyclin complexes 與細胞週期的運轉。透過抑制ATR/ATM-Chk1/Chk2 路徑，Wee1 蛋白或是DNA 修復酵素可以加劇DNA 的損傷，促進細胞減數分裂，最終導致有細胞死亡或衰老。
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| ATM inhibitors | |
| 貨號 | 品名 |
| 25648 | AZD 0156 |
| 16336 | Ku-55933 |
| 17502 | Ku-60019 |
| ATR inhibitors | |
| 貨號 | 品名 |
| 17589 | AZ 20 |
| 21035 | AZD 6738 |
| 17587 | VE-821 |
| Wee1 Inhibitors | |
| 貨號 | 品名 |
| 21266 | MK-1775 |
| 35391 | Wee1 Inhibitor |
| DNA Ligase Inhibitors | |
| 貨號 | 品名 |
| 18374 | L189 |
| 22941 | L67 |
| 18015 | SCR7 |
| Chk1 Inhibitors | |
| 貨號 | 品名 |
| 34300 | GDC-0575 |
| 20351 | LY2603618 |
| 21490 | LY2606368 |
| 17859 | PF-477736 |
| 18131 | SCH 900776 |
| 18130 | UCN-01 |
| Chk2 Inhibitors | |
| 貨號 | 品名 |
| 19178 | CCT241533 (hydrochloride) |
| 21184 | Chk2 Inhibitor |
| 19811 | NSC 109555 |
| PARP1 Inhibitors | |
| 貨號 | 品名 |
| 11505 | ABT-888 (hydrochloride) |
| 19782 | BMN 673 |
| 20842 | MK-4827 (tosylate) |
| 10621 | Olaparib |
| 33182 | Pamiparib |
| 15643 | Rucaparib |
紡錘體組裝檢查點 Spindle Assembly Checkpoint
當有絲分裂期間存在未連接或不正確連接的著絲點 (kinetochores) 時，紡錘體檢查點 (spindle checkpoint) 被激活，進而抑制促後期複合體 (anaphase-promoting complex/cyclosome, APC/C)，且避免細胞週期進展至後期階段。Mad2、BubR1、Bub3 以及 APC/C 共激活因子 - Cdc20 聚集在有絲分裂檢查點複合體 (mitotic checkpoint complex)，與激酶： Bub1、Mps1、Aurora B和 Plk1 共同參與 SAC 的調節。
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| Mitotic Checkpoint Complex Modulators | |
| 貨號 | 品名 |
| 17080 | Apcin |
| 22297 | M2I-1 |
| 17550 | N-4-Tosyl-L-arginine methyl ester (hydrochloride) |
| 25835 | proTAME |
| Mps1 Inhibitors | |
| 貨號 | 品名 |
| 19991 | AZ 3146 |
| 21660 | BAY 12-17389 |
| 19175 | Mps1-IN-1 |
| 25554 | Mps1/TTK Inhibitor |
| 31613 | NMS-P715 |
| 10004412 | Reversine |
| Plk1 Inhibitors | |
| 貨號 | 品名 |
| 17385 | BI-2536 |
| 18193 | BI-6727 |
| 18099 | GSK461364 |
| 15553 | ON-01910 (sodium salt) |
| 21669 | Ro 3280 |
| Aurora B Inhibitors | |
| 貨號 | 品名 |
| 13647 | AZD 1152 (hydrochloride) |
| 11602 | AZD 1152-HQPA |
| 24199 | Hesperadin |
| 13601 | ZM 447439 |
Modulators of Microtubule Dynamics
微管抑製劑(microtubule inhibitors) 結合β- 微管蛋白 (β-tubulin), 影響微管動力學和有絲分裂紡錘體结合， 活化紡錘體組裝檢查點。紫杉醇類 (Taxanes) 穩定微管（preexisting
microtubules)， 而長春花生物鹼 (Vinca alkaloids) 則防止微管聚合 (microtubules polymerization)。
| Taxanes | |
| 貨號 | 品名 |
| 22262 | Cabazitaxel |
| 11637 | Docetaxel (hydrate) |
| 10461 | Paclitaxel |
| 20741 | 7-epi Paclitaxel |
| Vinca Alkaloids | |
| 貨號 | 品名 |
| 11762 | Vinblastine (sulfate) |
| 11764 | Vincristine (sulfate) |
| 21262 | Vinorelbine (tartrate) |
其他相關試劑盒
| 貨號 | 品名 |
| 700160 | Myeloperoxidase (MPO) Peroxidation Fluorometric Assay Kit |
| 10006438 | Myeloperoxidase (MPO) Chlorination Fluorometric Assay Kit |
| 600450 | Glycolysis Cell-Based Assay Kit |
| 700470 | Pyruvate Assay Kit |
| 700510 | L-Lactate Assay Kit |
| 10011725 | Glycerol Cell-Based Assay Kit |
| 701350 | α-Ketoglutarate Fluorometric Detection Assay Kit |
| 10006908 | Adipogenesis Assay Kit |
| 10009381 | Adipolysis Assay Kit |
| 701490 | Deubiquitinases (DUB) Activity Assay Kit |
| 703202 | Glutathione Reductase Assay Kit |
| 703102 | Glutathione Peroxidase Assay Kit |
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