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Cell Cycle

Cell Cycle

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BI 2536

Catalog No. A10134
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PLK 抑制剂

BI 2536是Plk1的选择性抑制剂，可在低纳摩尔浓度下抑制Plk1酶的活性。了解更多

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- Kei K Ito, .et al. Cep57 and Cep57L1 maintain centriole engagement in interphase to ensure centriole duplication cycle, J Cell Biol, 2021, Mar 1;220(3):e202005153 PMID: 33492359
- Ryuzaburo Yuki, .et al. The tyrosine kinase v-Src modifies cytotoxicities of anticancer drugs targeting cell division, J Cell Mol Med, 2021, Feb;25(3):1677-1687 PMID: 33465289
- Yamagishi A, .et al. Targeting Insulin-Like Growth Factor 1 Receptor Delays M-Phase Progression and Synergizes with Aurora B Inhibition to Suppress Cell Proliferation, Int J Mol Sci, 2020, Feb 5;21(3) PMID: 32033461
- Bucko PJ, .et al. Subcellular drug targeting illuminates local kinase action, Elife, 2019, Dec 24;8. pii: e52220 PMID: 31872801
- Watanabe K, .et al. The Cep57-pericentrin module organizes PCM expansion and centriole engagement, Nat Commun, 2019, Feb 25;10(1):931 PMID: 30804344
- Valérian Pasche, .et al. Screening a repurposing library, the Medicines for Malaria Venture Stasis Box, against Schistosoma mansoni, Parasit Vectors, 2018, 11: 298 PMID: 29764454
- Takeshi Wakida, .et al. The CDK-PLK1 axis targets the DNA damage checkpoint sensor protein RAD9 to promote cell proliferation and tolerance to genotoxic stress, eLife, 2017, 6: e29953 PMID: 29254517
- Majid Momeny, .et al. Dacomitinib, a pan-inhibitor of ErbB receptors, suppresses growth and invasive capacity of chemoresistant ovarian carcinoma cells, Sci Rep, 2017, 7: 4204 PMID: 28646172
- Ifuji A, .et al. A novel immunofluorescence method to visualize microtubules in the antiparallel overlaps of microtubule-plus ends in the anaphase and telophase midzone, Exp Cell Res, 2017, Nov 15;360(2):347-357 PMID: 28942021
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SCH 900776 (MK-8776)

Catalog No. A11167
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Chk1 抑制剂

SCH 900776 (MK-8776)是靶向细胞周期检查点激酶1（Chk1）的药物，无细胞试验中IC50为3 nM，比作用于Chk2选择性高500倍。具有潜在的放射增敏和化学增敏活性。了解更多

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- Hong Yang, .et al. APOBEC3B Improves Response to PD-1 Blockade Through DSBs-ATR-CHK1 Pathway, Research Square, 2022, May 9th
- Motofumi Suzuki, .et al. Radiation-Induced Autophagy in Human Pancreatic Cancer Cells is Critically Dependent on G2 Checkpoint Activation: A Mechanism of Radioresistance in Pancreatic Cancer, Int J Radiat Oncol Biol Phys, 2021, May 25;S0360-3016(21)00361-8 PMID: 34112559
- Min Wu, .et al. FLT3/ITD Cooperates With Rac1 To Modulate The Sensitivity Of Leukemic Cells To Chemotherapeutic Agents Via Regulation Of DNA Repair Pathways, Haematologica, 2019, 104 PMID: 30975911
- Permata TBM, .et al. Base excision repair regulates PD-L1 expression in cancer cells, Oncogene, 2019, Feb 12 PMID: 30755733
- Hiro Sato, .et al. DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells, Nat Commun, 2017, 8: 1751 PMID: 29170499
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LY2603618 (IC-83)

Catalog No. A11036
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Chk 抑制剂

LY2603618 (IC-83)是一种chk2抑制剂，可与chk2结合并抑制其活性，这可能会阻止DNA损伤剂引起的DNA修复。了解更多

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- Hayakawa K, .et al. Planar compression of extracellular substrates induces S phase arrest via ATM-independent CHK2 activation, Biochem Biophys Res Commun, 2018, Dec 2;506(4):983-989 PMID: 30404732
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BI6727 (Volasertib)

Catalog No. A10135
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PLK 抑制剂

BI6727 (Volasertib)是一种高效且选择性的polo样激酶（PLK）1抑制剂（在一组癌细胞系中，酶IC50 = 0.87 nM，EC50 = 11-37 nM）。了解更多

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- Xiaofei Xin, .et al. ROS responsive polymeric micelles for triggered simultaneous delivery of PLK1 inhibitor/miR-34a and effective synergistic therapy in pancreatic cancer, ACS Appl Mater Interfaces, 2019, 2019
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GW843682X

Catalog No. A11438
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PLK1/PLK3 抑制剂

GW843682X是polo-like激酶1（PLK1）和polo-like激酶3（PLK3）的选择性抑制剂（IC50值分别为2.2和9.1 nM）。了解更多

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- Kanada F, .et al. Histone acetyltransferase and Polo-like kinase 3 inhibitors prevent rat galactose-induced cataract, Sci Rep, 2019, Dec 27;9(1):20085 PMID: 31882756
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GSK461364

Catalog No. A10442
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PLK 抑制剂

GSK461364 是polo样激酶1 (Plk1)的ATP竞争性抑制剂。了解更多

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HMN-214

Catalog No. A10452
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PLK 抑制剂

HMN-214抑制polo样和细胞周期蛋白依赖性激酶活性，具有强有力的抗微管作用，并在广泛的人类异种移植物中导致深度凋亡和抗肿瘤活性。了解更多

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TAK-960

Catalog No. A11146
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PLK1 抑制剂?

TAK-960是新型的，口服可用的polo样激酶1选择性抑制剂，具有广谱的临床前抗肿瘤活性。了解更多

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ON-01910 (rigosertib)

Catalog No. A10673
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PLK 抑制剂

ON-01910 (rigosertib)通过涉及PI3K/AKT抑制和氧化应激诱导的双重作用机制对慢性淋巴细胞白血病细胞具有选择性的细胞毒性。了解更多

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MLN 0905

Catalog No. A12429
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PLK1 抑制剂

MLN0905是有效的选择性小分子PLK1抑制剂。MLN0905抑制包括DLBCL细胞系在内的多种人类肿瘤细胞的细胞增殖。了解更多

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R1530

Catalog No. A13111
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Chk2, KDR, FGFR, Aurora A & Cdk2 抑制剂

R1530是吡唑并苯并二氮杂小分子，具有潜在的抗血管生成和抗肿瘤活性。R1530也是一种有丝分裂-血管生成抑制剂(MAI),可抑制多种参与血管生成的受体酪氨酸激酶，如血管内皮生长因子受体(VEGFR)-1，-2，-3，血小板衍生生长因子受体(PDGFR)βFMS样酪氨酸激酶(Flt)-3和成纤维细胞生长因子受体(FGFR) -1，-2。了解更多

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RO3280

Catalog No. A13245
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PLK1 抑制剂

RO3280是一种有效的，高选择性的Polo样激酶1（PLK1）抑制剂，IC50为3 nM。了解更多

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NMS-1286937

Catalog No. A13045
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PLK 抑制剂

NMS-1286937是一种小分子Polo样激酶1（PLK1）抑制剂，具有潜在的抗肿瘤活性。了解更多

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SBE 13 HCl

Catalog No. A14426
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PLK 抑制剂

SBE 13 HCl是PLK1的选择性抑制剂，对于PLK1，PLK3和PLK2，IC 50值分别为200pM，875nM和66μM。了解更多

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CCT241533 hydrochloride

Catalog No. A15038
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Chk2 抑制剂

CCT241533 hydrochloride是一种有效的丝氨酸/苏氨酸检查点激酶（Chk2）抑制剂，IC50为3 nM；显示在1 uM下与一组激酶的交叉反应最小。了解更多

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CCT244747

Catalog No. A15550
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CHK1 抑制剂

CCT244747是一种新型的有效，高选择性活性，ATP竞争性CHK1抑制剂，具有潜在的抗癌活性，了解更多

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SB 218078

Catalog No. A15480
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Chk1 抑制剂

SB 218078是检查点激酶1（Chk1）的抑制剂，对其他蛋白激酶具有选择性（Chk1，cdc2和PKC的IC50值分别为15、250和1000 nM）。了解更多

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AAPK-25

Catalog No. A19085
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Aurora/PLK dual 抑制剂

AAPK-25 is a potent and selective Aurora/PLK dual inhibitor with anti-tumor activity, which can cause mitotic delay and arrest cells in a prometaphase, reflecting by the biomarker histone H3Ser10 phosphorylation and followed by a surge in apoptosis. 了解更多

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Poloxime

Catalog No. A12145
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PLK1 inhibitor

Poloxime, a hydrolysis product of poloxin, is a non-ATP-competitive Plk1 inhibitor, with moderate Plk1 inhibitory activity. 了解更多

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CHK1-IN-2

Catalog No. A13142
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CHK1 inhibitor

CHK1-IN-2 is a checkpoint kinase 1 (CHK1) inhibitor, with an IC50 of 6 nM. 了解更多

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Poloxin

Catalog No. A11524
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PLK1 inhibitor

Poloxin is a non-ATP competitive Polo-like Kinase 1 (PLK1) inhibitor that targets the polo-box domain, with an IC50 of appr 4.8 μM. 了解更多

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Centrinone-B

Catalog No. A20855
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PLK4 inhibitor

Centrinone-B (LCR-323) is a potent and highly selective PLK4 inhibitor, with a Ki of 0.59 nM. 了解更多

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Centrinone

Catalog No. A20858
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PLK4 inhibitor

Centrinone (LCR-263) is a selective and reversible inhibitor of polo-like kinase 4 (PLK4) with a Ki of 0.16 nM. 了解更多

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GDC-0575 dihydrochloride

Catalog No. A21567
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CHK1 inhibitor

GDC-0575 dihydrochloride (ARRY-575 dihydrochloride) is an orally bioavailable CHK1 inhibitor, with an IC50 of 1.2 nM, and has antitumor activity. 了解更多

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SBE13

Catalog No. A21696
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Plk1 inhibitor

SBE13 is a potent and selective Plk1 inhibitor, with an IC50 of 200 pM; SBE13 poorly inhibits Plk2 (IC50>66?μM) or Plk3 (IC50=875?nM). 了解更多

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TAK-960 hydrochloride

Catalog No. A21703
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PLK1 inhibitor

TAK-960 hydrochloride is an orally available, selective inhibitor of polo-like kinase 1 (PLK1), with an IC50 of 0.8 nM at 10 μM ATP; TAK-960 hydrochloride also shows inhibitory activities against PLK2 and PLK3, with IC50s of 16.9 and 50.2 nM, respectively. 了解更多

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AZD7762

Catalog No. A10113
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Chk1 & Chk2 抑制剂

AZD7762是一种有效的ATP竞争性检查点激酶抑制剂，可促进检查点废止并增强DNA靶向疗法。了解更多

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CHIR-124

Catalog No. A11046
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CHK 抑制剂

CHIR-124是一种新型有效的Chk1抑制剂（Chk1和Chk2的IC50：分别为0.32 nM和697 nM）。了解更多

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CCT241533

Catalog No. A11108
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Chk2 抑制剂

CCT241533是CHK2的有效和选择性抑制剂，可增强PARP抑制剂的细胞毒性。了解更多

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PF 477736

Catalog No. A11520
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Chk 抑制剂

PF 477736是选择性检查点激酶1 (Chk1)抑制剂(Chk1和Chk2的ki值分别为0.49和47 nM)。了解更多

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SCH900776 (S-isomer)

Catalog No. A12703
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CHK1 抑制剂

SCH900776 (S-isomer)是靶向细胞周期检查点激酶1（Chk1）抑制剂，无细胞试验中IC50为3 nM，比作用于Chk2选择性高500倍。具有潜在的放射增敏和化学增敏活性。了解更多

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BML-277

Catalog No. A13575
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Chk2 抑制剂

BML-277（Chk2抑制剂II）是Chk2（检查点激酶2）抑制剂。了解更多

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GNE-900

Catalog No. A14178
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Chk1 抑制剂

GNE-900是一种ATP竞争性、选择性和生物可利用的chk1抑制剂。了解更多

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LY2606368

Catalog No. A13684
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Chk1 抑制剂

LY2606368是具有潜在抗肿瘤活性的检查点激酶1（chk1）抑制剂。了解更多

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PD0166285

Catalog No. A15863
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Wee1 抑制剂

PD0166285是一种有效的Wee1和Chk1抑制剂，在纳摩尔浓度下具有活性。PD0166285是一种新型的G2检查点消除剂。了解更多

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GDC-0575 (ARRY-575, RG7741)

Catalog No. A16811
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Chk1 抑制剂

GDC-0575 (ARRY-575,RG7741)是一种有效的选择性CHK1抑制剂，IC50为1.2 nM。了解更多

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CCT245737

Catalog No. A17239
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CHK1 inhibitor

CCT245737 is a potent, selective and orally active checkpoint kinase 1 (CHK1) inhibitor. CCT245737 showed CHK1 IC50 = 1.3 nM, CHK2 IC50 = 2440 nM, G2 check point abrogation IC50 = 30 nM. Mouse F (oral)=100%. 了解更多

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CHK1-IN-3

Catalog No. A18443
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CHK1 inhibitor

CHK1-IN-3 is a Checkpoint Kinase 1 (CHK1) inhibitor with an IC50 of 0.4 nM. 了解更多

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Palbociclib

Catalog No. A14427
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CDK 抑制剂

Palbociclib是一种吡啶并嘧啶衍生的细胞周期蛋白依赖性激酶（CDK）抑制剂，具有潜在的抗肿瘤活性。了解更多

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- Kana Nakatani, .et al. Inhibition of CDK4/6 and autophagy synergistically induces apoptosis in t(8;21) acute myeloid leukemia cells, Int J Hematol, 2020, Oct 17 PMID: 33068248
- Ryohei Ogata, .et al. Resistance to cyclin-dependent kinase (CDK) 4/6 inhibitors confers cross-resistance to other CDK inhibitors but not to chemotherapeutic agents in breast cancer cells, Breast Cancer, 2020, Aug 28 PMID: 32860163
- Kishino E, .et al. Anti-cell growth and anti-cancer stem cell activity of the CDK4/6 inhibitor palbociclib in breast cancer cells, Breast Cancer, 2019, Dec 10 PMID: 31823286
- Hidemasa Matsuo, .et al. Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia, Blood Adv, 2018, Nov 13; 2(21): 2879-2889 PMID: 30381403
- Zhihong Li, .et al. Discovery of AMG 925, a FLT3 and CDK4 dual kinase inhibitor with preferential affinity for the activated state of FLT3, J Med Chem, 2014, Apr 24;57(8):3430-49 PMID: 24641103
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LY2835219 (abemaciclib)

Catalog No. A12989
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CDK4/6 抑制剂

LY2835219 (abemaciclib)是一种细胞周期蛋白依赖性激酶（CDK）抑制剂，靶向CDK4（cyclin D1）和CDK6（cyclin D3）细胞周期途径，具有潜在的抗肿瘤活性。了解更多

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- Yoshinori Tanaka, .et al. Abemaciclib and Vacuolin-1 induce vacuole-like autolysosome formation - A new tool to study autophagosome-lysosome fusion, Biochem Biophys Res Commun, 2022, Jul 23;614:191-97 PMID: 35598430
- Sumire Suzuki, .et al. Lysosome-targeted drug combination induces multiple organelle dysfunctions and non?canonical death in pancreatic cancer cells, Oncol Rep, 2022, Feb;47(2):40 PMID: 34958115
- Kana Nakatani, .et al. Inhibition of CDK4/6 and autophagy synergistically induces apoptosis in t(8;21) acute myeloid leukemia cells, Int J Hematol, 2020, Oct 17 PMID: 33068248
- Ryohei Ogata, .et al. Resistance to cyclin-dependent kinase (CDK) 4/6 inhibitors confers cross-resistance to other CDK inhibitors but not to chemotherapeutic agents in breast cancer cells, Breast Cancer, 2020, Aug 28 PMID: 32860163
- Elaheh Seyed Abutorabi, .et al. Abemaciclib (CDK4/6 Inhibitor) Blockade Induces Cytotoxicity in Human Anaplastic Thyroid Carcinoma Cells, Rep Biochem Mol Biol, 2020, Jan; 8(4): 438-445 PMID: 32582803
- Hidemasa Matsuo, .et al. Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia, Blood Adv, 2018, Nov 13; 2(21): 2879-2889 PMID: 30381403
- Iriyama N, .et al. The cyclin-dependent kinase 4/6 inhibitor, abemaciclib, exerts dose-dependent cytostatic and cytocidal effects and induces autophagy in multiple myeloma cells, Leuk Lymphoma, 2018, Jun;59(6):1439-1450 PMID: 28918692
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PD 0332991 HCl (Palbociclib)

Catalog No. A10701
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CDK 4/6 抑制剂

PD 0332991 HCl (Palbociclib)是一种高度选择性的CDK4/6抑制剂，它对CDK1/2/5，EGFR，FGFR，PDGFR，InsR等没有抑制活性，具有潜在的抗肿瘤活性。了解更多

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- Hiroki Ozawa, .et al. Targeting AURKA in treatment of peritoneal tumor dissemination in gastrointestinal cancer, Transl Oncol, 2022, Feb;16:101307 PMID: 34902741
- Cong Li, .et al. AMG 925 is a dual FLT3/CDK4 inhibitor with the potential to overcome FLT3 inhibitor resistance in acute myeloid leukemia., Mol Cancer Ther., 2015, Feb;14(2):375-83. PMID: 25487917
- Pirita Pekkonen, .et al. KSHV viral cyclin interferes with T-cell development and induces lymphoma through Cdk6 and Notch activation in vivo, Cell Cycle, 2014, Dec 1; 13(23): 3670-3684 PMID: 25483078
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Flavopiridol (Alvocidib)

Catalog No. A10390
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CDK 抑制剂

Flavopiridol（Alvocidib）是一种细胞周期蛋白依赖性激酶抑制剂，与ATP竞争性抑制CDK，包括CDK1， CDK2， CDK4和CDK6，CDK9。作用于CDK1， 2， 4， 6，9比作用于CDK7更具有选择性，用于治疗慢性淋巴细胞性白血病。了解更多

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- Reiko Watanabe, .et al. Development of an In Silico Prediction Model for P-glycoprotein Efflux Potential in Brain Capillary Endothelial Cells toward the Prediction of Brain Penetration, J Med Chem, 2021, Mar 11;64(5):2725-2738 PMID: 33619967
- Zhiyuan Zhao, .et al. CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes, J Biol Chem, 2017, Sep 15; 292(37): 15489-15500 PMID: 28743741
- Sami Kukkonen, .et al. HIV-1 Tat second exon limits the extent of Tat-mediated modulation of interferon-stimulated genes in antigen presenting cells, Retrovirology., 2014, 11: 30. PMID: 24742347
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A-674563

Catalog No. A11034
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Akt 抑制剂

A-674563是一种B/Akt抑制剂，IC50为14 nM，并且还显示出对PKA和CDK2的抑制活性，IC50分别为16和46 nM。了解更多

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- Kobayashi T, .et al. A-674563 increases chondrocyte marker expression in cultured chondrocytes by inhibiting Sox9 degradation, Biochem Biophys Res Commun, 2018, Jan 1;495(1):1468-1475 PMID: 29196261
- Lin Xu, .et al. Concurrent targeting Akt and sphingosine kinase 1 by A-674563 in acute myeloid leukemia cells, Biochem Biophys Res Commun, 2016, Apr 15;472(4):662-8 PMID: 26920060
- Zou Y, .et al. Pre-clinical assessment of A-674563 as an anti-melanoma agent, Biochem Biophys Res Commun, 2016, Aug 12;477(1):1-8 PMID: 26970307
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Dinaciclib (SCH 727965)

Catalog No. A11129
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CDK 抑制剂

Dinaciclib (SCH 727965)是一种有效且选择性的细胞周期蛋白依赖性激酶（CDK）抑制剂，选择性抑制CDK1，CDK2，CDK5和CDK9，IC50值分别为3、1、1和4 nM。了解更多

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- Sepideh Izadi, .et al. Codelivery of HIF-1α siRNA and Dinaciclib by Carboxylated Graphene Oxide-Trimethyl Chitosan-Hyaluronate Nanoparticles Significantly Suppresses Cancer Cell Progression, Pharm Res, 2020, Sep 17;37(10):196 PMID: 32944844
- Shahin Hallaj, .et al. Inhibition of CD73 using folate targeted nanoparticles carrying anti-CD73 siRNA potentiates anticancer efficacy of Dinaciclib, Life Sci, 2020, Jul 26 PMID: 32726663
- Washio I, .et al. Impact of Breast Cancer Resistance Protein Expression on the In Vitro Efficacy of Anticancer Drugs in Pancreatic Cancer Cell Lines, Drug Metab Dispos, 2018, Mar;46(3):214-222 PMID: 29246888
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BAY 1000394 (Roniciclib)

Catalog No. A12742
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CDK 抑制剂

BAY 1000394 (Roniciclib)是一种口服生物利用细胞周期蛋白依赖性激酶（CDK）抑制剂，具有潜在的抗肿瘤活性。了解更多

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- Marzia Ognibene, .et al. Roniciclib down-regulates stemness and inhibits cell growth by inducing nucleolar stress in neuroblastoma, Sci Rep, 2020, 10: 12902 PMID: 32737364
- Xinan (Holly) Yang, .et al. A c-Myc-regulated stem cell-like signature in high-risk neuroblastoma: A systematic discovery (Target neuroblastoma ESC-like signature), Sci Rep, 2017, 7: 41 PMID: 28246384
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PHA-793887

Catalog No. A10716
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CDK 抑制剂

PHA-793887是一种新型有效的CDK2，CDK5和CDK7抑制剂，IC50分别为8 nM，5 nM 和10 nM，作用于CDK2，5，和7比作用于CDK1，4，和9选择性高6倍以上。可在低浓度下靶向多种细胞周期蛋白依赖性激酶，并具有针对多种癌细胞的高活性。了解更多

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- Hirosumi Tamura, .et al. Evaluation of anticancer agents using patient-derived tumor organoids characteristically similar to source tissues, Oncol Rep, 2018, Aug; 40(2): 635-646 PMID: 29917168
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Roscovitine (Seliciclib)

Catalog No. A10806
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CDK 抑制剂

Roscovitine (Seliciclib)是一种CDK抑制剂，可优先抑制多种酶靶标，包括CDK2，CDK7和CDK9。了解更多

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- Reiko Watanabe, .et al. Development of an In Silico Prediction Model for P-glycoprotein Efflux Potential in Brain Capillary Endothelial Cells toward the Prediction of Brain Penetration, J Med Chem, 2021, Mar 11;64(5):2725-2738 PMID: 33619967
- Vimal Pandey, .et al. Roscovitine effectively enhances antitumor activity of temozolomide in vitro and in vivo mediated by increased autophagy and Caspase-3 dependent apoptosis, Scientific Reports, 2019, 9, Article number: 5012 PMID: 30899038
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PHA-767491

Catalog No. A11164
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Cdc7/cdk9 抑制剂

PHA-767491是一种有效的，具有ATP竞争性的双重cdc7/cdk9抑制剂 (IC50值分别为10和34 nM)，可防止DNA复制的启动。了解更多

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- Lei Tan, .et al. Homologous recombination technology generated recombinant pseudorabies virus expressing EGFP facilitates to evaluate its susceptibility to different cells and screen antiviral compounds, Res Vet Sci, 2022, 145: 125-134 PMID: 35190327
- Qi Li, .et al. CDC7-dependent transcriptional regulation of RAD54L is essential for tumorigenicity and radio-resistance of glioblastoma, Transl Oncol, 2018, Apr; 11(2): 300-306 PMID: 29413763
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Kenpaullone

Catalog No. A11220
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CDK 抑制剂

Kenpaullone是CDK1/细胞周期蛋白B（IC 50 = 400 nM），CDK2/细胞周期蛋白A（IC 50 = 680nM），CDK5（IC 50 = 850nM）的有效抑制剂，对其他激酶的作用要小得多。了解更多

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- Katelyn M Green, .et al. High-throughput screening yields several small-molecule inhibitors of repeat-associated non-AUG translation, J Biol Chem, 2019, jbc.RA119.009951
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BMS-863233 (XL-413)

Catalog No. A13677
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CDK 抑制剂

BMS-863233，也称为XL-413，是一种具有潜在抗肿瘤活性的细胞分裂周期7同系物（CDC7）激酶抑制剂。了解更多

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- Gijs Zonderland, .et al. The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition, Mol Cell, 2022, Sep 15;82(18):3350-3365 PMID: 36049481
- Wang C, .et al. Inducing and exploiting vulnerabilities for the treatment of liver cancer, Nature, 2019, Oct 2 PMID: 31578521

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