Adavosertib (MK-1775)

For research use only. Not for use in humans.

目录号：S1525 别名： AZD1775

Adavosertib (MK-1775) Chemical Structure

CAS No. 955365-80-7

Adavosertib (MK-1775, AZD1775)是一种有效的，高选择性Wee1抑制剂，无细胞试验中IC50为5.2 nM；阻碍G2期DNA损伤检验点。Phase 2。

规格

价格

库存

购买数量

10mM (1mL in DMSO)	RMB 1960.96	现货
5mg	RMB 1376.38	现货
10mg	RMB 2226.67	现货
25mg	RMB 3835.28	现货
50mg	RMB 6297.29	现货
100mg	RMB 9582.3	现货
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客户使用Selleck生产的Adavosertib (MK-1775)发表文献146篇：

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JCI Insight, 2020, 143474

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Cancers (Basel), 2020, 12(6):1503

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FEBS J, 2020, 10.1111/febs.15280

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Nat Commun, 2019, 10(1):2189

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Elife, 2019, e46902

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Cancers (Basel), 2019, 11(11)

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Cancers (Basel), 2019, 11(6)

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Cells, 2019, 8(2)

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Cell Chem Biol, 2019, 10.1016/j.chembiol.2019.10.013

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Oncoimmunology, 2019, 8(11):e1638207

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Mol Cancer Ther, 2019, 18(8):1439-1450

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Gastric Cancer, 2019, 10.1007/s10120-019-00977-1

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Hum Mol Genet, 2019, 28(5):842-857

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Eur J Med Chem, 2019, 161:479-492

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J Virol, 2019, 93(14)

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Sci Rep, 2019,

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Front Pharmacol, 2019, 10:864

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Exp Cell Res, 2019, 111720

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PLoS One, 2019, 14(2):e0212210

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Biochem Biophys Res Commun, 2019, 10.1016/j.bbrc.2019.10.124

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Blood Adv, 2019, 3(7):1185-1196

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Leukemia, 2019, 10.1038/s41375-019-0677-4

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Nat Commun, 2018, 9(1):3982

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Nucleic Acids Res, 2018, 46(10):5109-5124

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J Immunother Cancer, 2018, 6(1):59

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Cancer Res, 2018, 78(11):3054-3066

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Cell Rep, 2018, 22(12):3206-3216

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Cancer Lett, 2018, 430:34-46

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J Exp Clin Cancer Res, 2018, 37(1):129

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Cancers (Basel), 2018, 10(5)

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Curr Biol, 2018, 28(23):3824-3832

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Cells, 2018, 7(9)

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Front Oncol, 2018, 8:143

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Sci Rep, 2018, 8(1):948

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Int J Biol Sci, 2018, 14(10):1221-1231

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BMC Cancer, 2018, 18(1):922

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PLoS One, 2018, 13(2):e0193098

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Biomed Res Int, 2018, 2018:5813292

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Oncol Lett, 2018, 16(4):5473-5481

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SSRN, 2018, 10.2139/ssrn.3188455

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Blood, 2017, 130(24):2631-2641

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Genes Dev, 2017, 31(3):318-332

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Aging Cell, 2017, 16(3):575-584

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J Hematol Oncol, 2017, 10(1):77

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J Med Chem, 2017, 60(18):7863-7875

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Br J Cancer, 2017, 117(1):113-123

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Mol Cancer Ther, 2017, 16(9):2022-2034

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Sci Rep, 2017, 7:43517

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Oncotarget, 2017, 8(43):73705-73722

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Clin Cancer Res, 2016, 22(17):4440-51

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Sci Rep, 2016, 6:33323

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BMC Cancer, 2016, 16:678

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Genes Dev, 2015, 29(5):555-66

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Cancer Biol Ther, 2015, 16(12):1784-93

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Cell Cycle, 2015, 14(7):1070-81

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Pediatr Blood Cancer, 2015, 62(1):52-9

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产品安全说明书

Wee1抑制剂选择性比较

生物活性

产品描述

Adavosertib (MK-1775, AZD1775)是一种有效的，高选择性Wee1抑制剂，无细胞试验中IC50为5.2 nM；阻碍G2期DNA损伤检验点。Phase 2。

特性

首个报道的 Wee1抑制剂。

靶点

Wee1 ^[1]
(Cell-free assay)

5.2 nM

体外研究

MK-1775以ATP竞争的方式抑制Wee1激酶。与作用于Wee1相比，MK-1775对Yes的效能低2-到3-倍，IC50为14 nM，对7种其他激酶的效能低10倍，1 μM浓度下抑制率>80%，比对人Myt 1选择性高100倍以上，并抑制周期蛋白依赖性激酶1 (CDC2) 在可选择位点(Thr14) 的磷酸化作用。通过阻断负荷突变型p53的WiDr细胞中Wee1活性，废止DNA损伤检控点，MK-1775治疗抑制Tyr15 (CDC2Y15)位点的CDC2基础磷酸化作用，EC50为49 nM，并剂量依赖性抑制gemcitabine-，carboplatin- 或cisplatin-诱导的CDC2磷酸化和细胞周期阻滞，EC50分别为82 nM和81 nM，180 nM 和163 nM，以及159 nM 和 160 nM。30-100 nM 的MK-1775单独治疗在WiDr 和 H1299细胞中没有显著的抗增殖作用，而300 nM的MK-1775足以抑制>80%的Wee1，表现出温和但显著的抗增殖作用，在WiDr和H1299细胞中抑制率分别为34.1%和28.4%。^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
ASPC-1	M2fQV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NUCzdmZOUUN3ME2xN{4zKMLzIEGuNUDPxE1?	MnrwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV2NUi5OVQoRjJ3NEW4PVU1RC:jPh?=
BxPC-3	NYTWe483T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NEDXdWhKSzVyPUCuPEDDuSByLkCzJO69VQ>?	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTR3OEm1OEc,OjV2NUi5OVQ9N2F-
CFPAC-1	NHLkc5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NWTnO5FQUUN3ME2zMlMhyrFiMD6yJO69VQ>?	NWLhU5hERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW0OVg6PTRpPkK1OFU5QTV2PD;hQi=>
HPAC	MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MnHITWM2OD1yLkWgxtEhOC5yMTFOwG0>	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTR3OEm1OEc,OjV2NUi5OVQ9N2F-
MIAPaCa-2	M37LfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MX;JR\|UxRTBwNTFCtUAxNjB3IN88US=>	M3HZOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NEW4PVU1Lz5{NUS1PFk2PDxxYU6=
PANC-1	MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MmTkTWM2OD1zMD62JOKyKDFwMTFOwG0>	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTR3OEm1OEc,OjV2NUi5OVQ9N2F-
SK-N-BE (2)	MmnIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NGnONYhKSzVyPUKuOQKBkcLz4pEJNE4{KM7:TR?=	NXfwW3J[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWzNFg6OTZpPkK1N\|A5QTF4PD;hQi=>
SK-N-BE (2), PAN→MK	NWXEZXdrT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MWLJR\|UxRTJ4LkdihKnDueLCiUmuOkDPxE1?	M{jC[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{C4PVE3Lz5{NUOwPFkyPjxxYU6=
SK-N-BE (2), MK→PAN	M4fSWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NVzsd4p2UUN3ME2yMlTjiIoEsfMAjVAvOyEQvF2=	Mnq2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV\|MEi5NVYoRjJ3M{C4PVE3RC:jPh?=
SK-N-AS	MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NFTFOY9KSzVyPUCuOVDjiIoEsfMAjVAvODJizszN	MlXQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV\|MEi5NVYoRjJ3M{C4PVE3RC:jPh?=
SK-N-DZ	NGHwfIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NWDvV2p4UUN3ME2wMlM36oDLwsJihKkxNjBzIN88US=>	NFT2WIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPFkyPid-MkWzNFg6OTZ:L3G+
SK-N-AS	NV3HNoZUSXCxcITvd4l{KEG\|c3H5	NWe1ZYE1PTByIH7N	Mnm3OFghcA>?	MX;pcoR2[2W\|IHPlcIwh[XCxcITvd4l{	NIflVHE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPFkyPid-MkWzNFg6OTZ:L3G+
SK-N-DZ	M3z0RmFxd3C2b4Ppd{BCe3OjeR?=	NEj0[ng2ODBibl2=	MojtOFghcA>?	NIOyV\|dqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	M1rMUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{C4PVE3Lz5{NUOwPFkyPjxxYU6=
THP-1	Mkf2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MoWxNVI2NzJ3MD:1NFAhdk1?	M3nMb\|Q5KGh?	NF;BPGNqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>?	M1\zTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEi0OlE1Lz5{NUC4OFYyPDxxYU6=
MV4-11	MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MoDrNVI2NzJ3MD:1NFAhdk1?	NUfsfJVtPDhiaB?=	MXHpcoNz\WG\|ZYOgZ4VtdCCmZXH0bEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=>	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB6NE[xOEc,OjVyOES2NVQ9N2F-
U937	M{Tmbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NXrtXFNGOTJ3L{K1NE82ODBibl2=	NXXnd3UxPDhiaB?=	NH;yW4hqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>?	NW\kXm4xRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwPFQ3OTRpPkK1NFg1PjF2PD;hQi=>
HL-60	NVrMe5pKT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MmXpNVI2NzJ3MD:1NFAhdk1?	NYHmPJNrPDhiaB?=	MlrmbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI>	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB6NE[xOEc,OjVyOES2NVQ9N2F-
OCI-AML3	NEHSTo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MonONVI2NzJ3MD:1NFAhdk1?	NH7IO\|k1QCCq	NGfBeHFqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>?	MmLwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyOES2NVQoRjJ3MEi0OlE1RC:jPh?=
MOLM-13	M3OxWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NYPDWJhZOTJ3L{K1NE82ODBibl2=	NWjQ[ph2PDhiaB?=	MkPpbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI>	M{LGZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEi0OlE1Lz5{NUC4OFYyPDxxYU6=
CMK	MnS4R4VtdCCYaXHibYxqfHliQYPzZZk>	MofxNVAuOTByMECgcm0>	Mmq2O\|IhcA>?	NX;WTmZmemWmdXPld{Bk\WyuII\pZYxq[mm2eTDpckBiKGOxbnPlcpRz[XSrb36t[IVx\W6mZX70JI1idm6nch?=	MmTSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7NkKzN\|EoRjJ2OU[yN\|MyRC:jPh?=
CMY	NX;5N\|FMS2WubDDWbYFjcWyrdImgRZN{[Xl?	MVixNE0yODByMDDuUS=>	M1;E[lczKGh?	NYq1OJNxemWmdXPld{Bk\WyuII\pZYxq[mm2eTDpckBiKGOxbnPlcpRz[XSrb36t[IVx\W6mZX70JI1idm6nch?=	NY\Jd2t1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5OlI{OzFpPkK0PVYzOzNzPD;hQi=>
Dayo	NHLud4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MYPJR\|UxRTF3MDDuUS=>	MoH5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NkG5NVAoRjJ2Nk[xPVExRC:jPh?=
UW228	MkKwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MV;JR\|UxRTJ\|MjDuUS=>	NWDoWnN[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2OlE6OTBpPkK0OlYyQTFyPD;hQi=>
IST-MES1	MXLD[YxtKF[rYXLpcIl1gSCDc4PhfS=>	NULHNYoyOTVyL{K1NEBvVQ>?	MWC3NkBp	NULabJpx\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{	NWLQS2ZVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlU4QDJpPkK0N\|Y2Pzh{PD;hQi=>
IST-MES2	Ml6xR4VtdCCYaXHibYxqfHliQYPzZZk>	NVHqcIZ4OTVyL{K1NEBvVQ>?	MVO3NkBp	M1TFb4VvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>?	NWW4NVFkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlU4QDJpPkK0N\|Y2Pzh{PD;hQi=>
REN	NETtWolE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MmDkNVUxNzJ3MDDuUS=>	MWW3NkBp	NYfqO\|ZF\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{	NVjvd2Y1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlU4QDJpPkK0N\|Y2Pzh{PD;hQi=>
NCI-H2452	M4O0dWNmdGxiVnnhZoltcXS7IFHzd4F6	MoDWNVUxNzJ3MDDuUS=>	MlvGO\|IhcA>?	NESwe5ZmdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ?	M4n5c\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{[1O\|gzLz5{NEO2OVc5OjxxYU6=
MSTO-211H	M1j1fGNmdGxiVnnhZoltcXS7IFHzd4F6	NUjvenhVOTVyL{K1NEBvVQ>?	NWfNOIlDPzJiaB?=	MW\lcohidmOnczD0bIUh[2m\|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI>	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN4NUe4Nkc,OjR\|NkW3PFI9N2F-
NCI-H2052	M4\p[GNmdGxiVnnhZoltcXS7IFHzd4F6	MVuxOVAwOjVyIH7N	MUW3NkBp	NYryPY5F\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{	NFHmcmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO2OVc5Oid-MkSzOlU4QDJ:L3G+
WEE1	NFTjOphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NV25VJBUUUN3ME21MlIhdk1?	M2nBVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|Nkm5OlU2Lz5{M{[5PVY2PTxxYU6=
CDC2	NVnLbG1lT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M3;M[WlEPTExvK6xNFAxKG6P	MnL5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4OUm2OVUoRjJ\|Nkm5OlU2RC:jPh?=
CDK7	MnjPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MYPJR\|Ux97zgMUCwNEBvVQ>?	MnjHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4OUm2OVUoRjJ\|Nkm5OlU2RC:jPh?=
MYT1	MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NXXhdpFpUUN3ME21N\|Ahdk1?	M4HE[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|Nkm5OlU2Lz5{M{[5PVY2PTxxYU6=
T98G	MlLiRZBweHSxc3nzJGF{e2G7	MlyxNVAxNzJ3MDDuUS=>	MUS2JIg>	M{j3doVvcGGwY3XzJJJi\GmjdHnvck1qdmS3Y3XkJINmdGxia3nscIlv\w>?	M1LCblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUmyO\|k{Lz5{MUm5Nlc6OzxxYU6=
A549	MWLBdI9xfG:\|aYOgRZN{[Xl?	MWeyNFAhdk1?	NUDpT\|h7OSCq	MXzyZYRqd3OnboPpeIl7\XNiTmPDUGMh[2WubIOgbY4h[SCyNUOt[IVx\W6mZX70JI1idm6nch?=	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTd7OUCzN{c,OjF5OUmwN\|M9N2F-
H460	NYrWdZlNSXCxcITvd4l{KEG\|c3H5	M3nQUVIxOCCwTR?=	MmTTNUBp	NVr3WWRsemGmaX;z[Y5{cXSrenXzJG5US0yFIHPlcIx{KGmwIHGgdFU{NWSncHXu[IVvfCCvYX7u[ZI>	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTd7OUCzN{c,OjF5OUmwN\|M9N2F-
H1299	MmfLRZBweHSxc3nzJGF{e2G7	NWq5Z4g2OjByIH7N	NIXaR3YyKGh?	NXzXfmVJemGmaX;z[Y5{cXSrenXzJG5US0yFIHPlcIx{KGmwIHGgdFU{NWSncHXu[IVvfCCvYX7u[ZI>	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTd7OUCzN{c,OjF5OUmwN\|M9N2F-
Calu-6	NHTud3hCeG:ydH;zbZMhSXO\|YYm=	MkfNNlAxKG6P	MWSxJIg>	Mmq0doFlcW:\|ZX7zbZRqgmW\|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK=	NIfmd409[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUe5PVA{Oyd-MkG3PVkxOzN:L3G+
WiDr	NFPybXJMcW6jc3WgRZN{[Xm\|	NVXDeYhHOTBvMUCwNFAhdk1?	MoDKPEBp	NIHieVlqdmirYnn0d{BxcG:\|cHjvdplt[XSrb36gc4YhS0SFMjDheEBVgXJzNTD3bZRpKGGwIFXDOVDDqH[jbIXlJI9nKDh3IH7tc4wwVCCycnX0doVifGWmIIfpeIgh\2WvY3n0ZYJqdmV?	NV6zenZHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm4PFc2PDVpPkG5PFg4PTR3PD;hQi=>
Function assay	MmnPSZhxcTJ7M1[=			MV;CbY5lcW6pIHHm[olvcXS7IITvJJJm[2:vYnnuZY51KGi3bXHuJIZ2dGxvbHXu[5RpKE5vdHXycYlv[WxiSHnzPE11[WepZXSgW4VmOSBqMTD0c{A3PDZicnXzbYR2\XNrIHX4dJJme3OnZDDpckBpfW2jbjDFfJBqOjl\|RjDj[YxteyCjc4Pld5Nm\CCjczDk[ZN{d2OrYYTpc44h[2:wc4ThcpQh[nlicYXhcpRqfGG2aY\lJJJm[WxvdHnt[UBRS1JibXX0bI9lNCCNZDC9JFAvODB\|MjFOwG0v	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd7Mke2NEc,Ojh5OUK3OlA9N2F-
Function assay	MXvFfJBqOjl\|Rh?=			MkXORolv\GmwZzDh[oZqdmm2eTD0c{Bz\WOxbXLpcoFvfCCqdX3hckBnfWyuLXzlcod1cCCQLYTldo1qdmGuIFjpd\|gufGGpZ3XkJHdm\TJiKEGgeI8hPTZ5IILld4llfWW\|KTDlfJBz\XO\|ZXSgbY4hcHWvYX6gSZhxcTJ7M1[gZ4VtdHNiYYPz[ZN{\WRiYYOg[IV{e2:laXH0bY9vKGOxboP0ZY51KGK7IIH1ZY51cXSjdHn2[UBz\WGuLYTpcYUhWEOUIH3leIhw\CxiS3SgQUAxNjByM{mg{txONg>?	NFf4eWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEe5Nlc3OCd-Mki3PVI4PjB:L3G+
Antiproliferative assay	NX7WXnlXVUSDLV3CMVI{OQ>?		M3fu[\|czKGi{cx?=	NXuycZdiSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvMkOxJINmdGy\|IH3lZZN2emWmIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygTWM2OCB;IECuNlYh\|ryPLh?=	NGHYOZA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEe5Nlc3OCd-Mki3PVI4PjB:L3G+
Antiproliferative assay	MXHISWszQTOW		MXe3NkBpenN?	NW\FNXRSSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBJTUt{OUPUJINmdGy\|IH3lZZN2emWmIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygTWM2OCB;IECuNlkh\|ryPLh?=	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd7Mke2NEc,Ojh5OUK3OlA9N2F-
Antiproliferative assay	MX3NUVFU		NGPjfIg4OiCqcoO=	MnPHRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPTUHTJINmdGy\|IH3lZZN2emWmIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygTWM2OCB;IECuN\|Eh\|ryPLh?=	NW\CdmNiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3PVI4PjBpPkK4O\|kzPzZyPD;hQi=>
Function assay	NUPKNXo{UEWNMkmz		MVWxJIhz	MnjmTY5pcWKrdHnvckBw\iCqdX3hckBnfWyuIHzlcod1cCCSS13ZWFEh\XiycnXzd4VlKGmwIFjFT\|I6OyClZXzsd{B2e2mwZzDFSnMhMDJ2NzD0c{AzPTlicnXzbYR2\XNrIHHzJJN2[nO2cnH0[UBi\nSncjCxJIhzKGK7IH\seY9z\XOlZX7j[UBxd2yjcnn6ZZRqd25iaX3teY5w[XOjeTygT4khRSByLkS3JO69VS5?	NXSwbWNlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm5OFEyQTNpPkK5PVQyOTl\|PD;hQi=>
Function assay	NWXoUVFyUEWNMkmz		NGTHTJUyKGi{	NWrZSW9bUW6qaXLpeIlwdiCxZjDoeY1idiCodXzsJIxmdme2aDDQT21[XDFiZYjwdoV{e2WmIHnuJGhGUzJ7MzDj[YxteyC3c3nu[{BGTlNiKEK0O{B1dyB{NUmgdoV{cWS3ZYOpJIF{KHO3YoP0doF1\SCjZoTldkAyKGi{IHL5JIZtfW:{ZYPj[Y5k\SCyb3zhdol7[XSrb36gbY1ufW6xYYPhfUwhUUN3MDC9JFQvQTRizszNMi=>	M3TMVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUSxNVk{Lz5{OUm0NVE6OzxxYU6=
Function assay	NXTQVXZMVUSDLV3CMVI{OQ>?	NVXx[mZ1OC5zIITvJFExKHWP	MmGwOkBpenN?	NYjRVnFlUW6qaXLpeIlwdiCxZjDX[YUyKGmwIHj1cYFvKE2GQT3NRk0zOzFiY3XscJMh[XO\|ZYPz[YQh[XNiZHXjdoVie2ViaX6gR2RMOSCyaH;zdIhwenmuYYTpc44h[XRiVInyJFE2KGG2IECuNUB1dyBzMDD1UUBi\nSncjC2JIhzeyCkeTDX[ZN1\XKwIHLsc5QhdWW2aH;k	NUTLTY1ERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3PVI4PjBpPkK4O\|kzPzZyPD;hQi=>
Function assay	MVjISWszQTOW	M{PKc\|AvOSC2bzCxNEB2VQ>?	NVKyT4FxPiCqcoO=	NWTG[nVRUW6qaXLpeIlwdiCxZjDX[YUyKGmwIFjFT\|I6O1RiY3XscJMh[XO\|ZYPz[YQh[XNiZHXjdoVie2ViaX6gR2RMOSCyaH;zdIhwenmuYYTpc44h[XRiVInyNVUh[XRiMD6xJJRwKDFyIIXNJIFnfGW{IE[gbJJ{KGK7IGfld5Rmem5iYnzveEBu\XSqb3S=	MonnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5OUK3OlAoRjJ6N{myO\|YxRC:jPh?=
Function assay	NV;mWVljUEWNMkmzWC=>	NGfxXpkxNjFidH:gNVAhfU1?	MYK2JIhzew>?	NUH6UY1EUW6qaXLpeIlwdiCxZjDQUGsyKGmwIFjFT\|I6O1RiY3XscJMh[XO\|ZYPz[YQh[XNiZHXjdoVie2ViaX6gWGNVWCCyaH;zdIhwenmuYYTpc44h[XRiMD6xJJRwKDFyIIXNJIFnfGW{IE[gbJJ{KGK7IGfld5Rmem5iYnzveEBu\XSqb3S=	NYPLPJRFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3PVI4PjBpPkK4O\|kzPzZyPD;hQi=>
Function assay	MXTNSGEuVUJvMkO=	NH3UUVMxNjFidH:gNVAhfU1?	NH7CZmo3KGi{cx?=	NGiy[VNKdmirYnn0bY9vKG:oIGDMT\|EhcW5iaIXtZY4hVUSDLV3CMVI{KGOnbHzzJIF{e2W\|c3XkJIF{KGSnY4LlZZNmKGmwIGTDWHAheGixc4Doc5J6dGG2aX;uJIF1KDBwMTD0c{AyOCC3TTDh[pRmeiB4IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m	NHTTfW89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEe5Nlc3OCd-Mki3PVI4PjB:L3G+
qHTS assay	M1jJcXREOzJ?			MVXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXEN\|MjDj[Yxtew>?	M3;Yc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay	NXvpUIxKXS1{IF;T			NYjIPYJNeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGWtNkBQWyClZXzsdy=>	MonsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay	M3jEZmE3PzN?			M3fTRpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCDNkezJINmdGy\|	NIDJO489[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
qHTS assay	M1fmNmRCV1l?			NUn0XpJ5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFTBU3kh[2WubIO=	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
qHTS assay	NGSyPXFU[W:\|LUK=			MnLhdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFOjb4OtNkBk\Wyucx?=	MoHRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay	NV[4c3lvSlRvM{e=			NH7U[2tyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQmStN\|ch[2WubIO=	NGLuVY49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
qHTS assay	NUPGSYlqWkR?			MljCdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKGIHPlcIx{	NHXUeGs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
qHTS assay	MmrwV2suVi2VSB?=			M1u3[pFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	Mn35QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay	M2fPOGJVNTF{			NGXrSJhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQmStNVIh[2WubIO=	M3nDWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay	NXq1TGw1VkJzNkSz			NFvPVVVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz	NGfpUHI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
qHTS assay	M3j6NG9JWy13MB?=			NHzJeWdyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiT1jTMVUxKGOnbHzz	NUPIWplTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay	MlLPRnQuOTJ?			NWD6OGl[eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	Ml\WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay	MnK2SGFQYQ>?			NYHDRYd1eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>?	M1nJNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay	M4XEcHNMNU5vU1i=			MnjBdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV2suVi2VSDDj[Yxtew>?	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
qHTS assay	NWj5U29HWmh2MR?=			M{fDeZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaESxJINmdGy\|	NHvMVZg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
qHTS assay	MY\BOlc{			NEXldo9yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBCPjd\|IHPlcIx{MQ>?	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
qHTS assay	MkDvUWchPjNiKE[tWGchWil?			NGf4WW1yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBOTyB4MzCoOk1VTyCUKTDj[Yxtew>?	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
qHTS assay	NIDtSoxWNTJiT2O=			M33xW5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHUuOiCRUzDj[Yxtew>?	MlvVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay	NEDLVI5QUFNvNUC=			NXvzVGwyeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	NYCwSVZrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay	NXfnXHhyWmh2MR?=			M174UZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpPDFiY3XscJM>	MkTXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay	MV7SSC=>			NV7qc5REeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhWkRiY3XscJM>	MnW0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay	MlLGV2ouT0KPMh?=			MYHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	M2XMfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay	NFPyXYpUUy2QLV3D			M33lVJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz	NHTKfXE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
qHTS assay	MYTORk1GSmNz			MonVdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6ELVXCZ\|Eh[2WubIO=	NEnnOJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
qHTS assay	NH:ySnpNSU5vNR?=			M{HYfJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCOQV6tOUBk\Wyucx?=	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
qHTS assay	NGH6fItTcDF6			NF[x[IZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnixPEBk\Wyucx?=	NEfOZ4w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
qHTS assay	Ml3lV2ouT0KPMh?=			MlfHdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV2ouT0KPMjDj[Yxtew>?	NXSxOmJJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay	NGG4SVdU[W:\|LUK=			M3TOOpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNid3NvMjDj[Yxtew>?	NVzCXWluRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-Cdk1(Y15) / Cdk1; PubMed: 25609063 Clin Cancer Res The impact of a 24 hour pre-treatment of MK-1775 on p-Cdk1 was assessed by western blotting. Because of low basal phosphorylation, GBM22 was irradiated (RT) with 10 Gy. p-KAP1(S824) / p-Chk2(T68) / p-Chk1(S345); PubMed: 25609063 Clin Cancer Res Western blot evaluation of GBM6 and GBM22 short-term explant cultures 24 hours after treatment with either MK-1775 or TMZ or the combination. PARP / CF-PARP / pH3(S10) / p-CDC25c(S216) / p-CDK2(Y15); PubMed: 25458954 Cancer Lett Pancreatic cancer cells were treated with vehicle control or 500 nM MK-1775 for 48 h. Whole cell lysates were subjected to Western blotting and probed with anti-PARP, -p-H3, -γH2AX, -p-CHK1, -CHK1, -p-CDC25C, -p-CDK1, - CDK1, -p-CDK2, -CDK2, or -β-actin antibody. WEE1; PubMed: 27616351 Sci Rep MIA PaCa2, PANC-1, Hs 766T, Capan-1 and PL11 cells were treated with MK-1775 (400 nM/L) and/or MMC (150 nM/L) for 24 hours. Whole cell lysates were prepared using RIPA and western blot was performed to assess the protein expression of WEE1 (90 kDa), pCDK1(y15) (34 kDa), CDK1 (34 kDa) and GAPDH (36 kDa) as loading control.	25609063 25458954 27616351
Immunofluorescence	tubulin / p-HH3(S10); PubMed: 30755439 Clin Cancer Res FaDu and UNC7 cells were treated with adavosertib (500 nM), alisertib (250 nM), or adavosertib + alisertib for 24 hours and followed by immunofluorescent staining with anti-tubulin (Green) and anti-pHH3 (S10; Red). Nucleus was stained with DAPI. (A) Representative images of mitotic cells were captured by confocal microscopy. Scale bar: 10 µm. γH2AX; PubMed: 25609063 Clin Cancer Res A) γH2AX foci formation in GBM6 and GBM22 were assessed 24 h after a single treatment of 300 nM MK-1775. Cleaved caspase-3 / pH3; PubMed: 27616351 Sci Rep MIA PaCa2 cells were treated and dual stained with pH3 to observe mitotic entry; and cleaved caspase 3 (CL-CSP3) to observe caspase 3 activity.	30755439 25609063 27616351
Growth inhibition assay	Cell viability; PubMed: 25458954 Cancer Lett Pancreatic cancer cell lines were cultured in 96-well plates at 37℃ for 48 h in complete medium with variable concentrations of MK-1775 and viable cell numbers were determined using MTT reagent and a microplate reader. The data are presented as means ± standard errors from at least 3 independent experiments. IC50; PubMed: 25084614 J Hematol Oncol AML cell lines were cultured for 72 h in complete medium with variable concentrations of MK-1775 (MK) and viable cell numbers were determined using MTT assays. IC50 values were calculated as drug concentration necessary to inhibit 50% growth compared to untreated control cells.	25458954 25084614

体内研究

MK-1775(~20 mg/kg)单独治疗对WiDr异种移植物表现出最小的抗肿瘤作用，在大鼠体内第3天时T/C为69%。在裸鼠HeLa-luc和TOV21G-shp53异种移植模型中，MK-1775单独的抗肿瘤效能是温和的。^[1]

激酶实验： ^[1]	- 合并体外激酶试验: 使用重组人Wee1。激酶反应使用10 μM ATP，1.0 μCi of [γ-³³P]ATP，和2.5 μg poly(Lys, Tyr)作为底物，在逐渐增加浓度的MK-1775存在下，在30°C环境中进行30分钟。整合到底物的放射性被捕获到MultiScreen-PH平板，在液体闪烁计数器上计数。
细胞实验： ^[1]	- 合并 Cell lines: WiDr，NCI-H1299，TOV21G，和 HeLa细胞 Concentrations: 在DMSO中溶解，终浓度为~10 μM Incubation Time: 24小时 Method: 细胞在gemcitabine存在或不存在下处理24小时，然后用MK-1775再处理24小时。细胞活性使用SpectraMax通过WST-8试剂盒测定。细胞内caspase-3/7活性使用Caspase-3/7 Glo试剂盒测定。 (Only for Reference)
动物实验： ^[1]	- 合并 Animal Models: 负荷WiDr，HeLa-luc，或TOV21G-shp53肿瘤的免疫缺陷裸鼠(F344/NJcl-rnu) Dosages: ~20 mg/kg/day Administration: 口服 (Only for Reference)

参考文献

[1] Hirai H, et al. Mol Cancer Ther, 2009, 8(11), 2992-3000.

溶解度 (25°C)

体外	DMSO	80 mg/mL (159.8 mM)
	Ethanol	10 mg/mL (19.97 mM)
	Water	0.0001 mg/mL (0.0 mM)
体内	从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 2% DMSO+30% PEG 300+5% Tween 80+ddH2O	5mg/mL

* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据 Download Adavosertib (MK-1775) SDF

分子量	500.6
化学式	C₂₇H₃₂N₈O₂
CAS号	955365-80-7
储存条件	3年-20°C 粉状 2年-80°C 溶于溶剂
别名	AZD1775

动物体内配方计算器 (澄清溶液)

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量

mg/kg

动物平均体重

每只动物给药体积

动物数量

只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO+ % + % Tween 80+ % ddH₂O

计算重置

计算结果:

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH₂O，混匀澄清。

注意：1. 首先保证母液是澄清的；
2. 一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

质量

浓度

体积

分子量
=

×

×

*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。

稀释计算器

用本工具协助配置特定浓度的溶液，使用的计算公式为：

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入输出 )

C1

V1

C2

V2
×

=

×

在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.

连续稀释计算器方程

连续稀释
初始浓度:
稀释倍数:

计算结果

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

分子量计算器

通过输入化合物的化学式来计算其分子量：

注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×
计算

临床试验信息 (data from https://clinicaltrials.gov, updated on 2021-05-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03668340	Recruiting	Drug: AZD1775	Uterine Cancer	Dana-Farber Cancer Institute\|AstraZeneca	October 22 2018	Phase 2
NCT03028766	Completed	Drug: AZD1775\|Drug: Cisplatin\|Radiation: Radiotherapy	Hypopharynx Squamous Cell Carcinoma\|Oral Cavity Squamous Cell Carcinoma\|Larynx Cancer	University of Birmingham\|AstraZeneca\|Cancer Research UK	June 22 2017	Phase 1
NCT02617277	Active not recruiting	Drug: AZD1775\|Drug: MEDI4736	Advanced Solid Tumours	AstraZeneca	December 28 2015	Phase 1

技术支持

在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题，请给我们留言。

常见问题及建议解决方法

问题 1：
How to prepare MK1775 methylcellulose solution? and how to prepare methylcellulose itself? Once make the MK1775 methylcellulose solution, how should i keep it?
回答：
MK1775 in 0.5% methylcellulose is a suspension or emulsion, and it is ok to treat mice orally. It is recommended to dissolve methylcellulose in saline. It will take some time to dissolve methylcellulose, and you can vortex it for a while. The MK1775 methylcellulose solution can be stored at 4°C for a week.

研究领域

产品类型

定制您的化合物库

Adavosertib (MK-1775)

客户使用Selleck生产的Adavosertib (MK-1775)发表文献146篇：

产品安全说明书

Wee1抑制剂选择性比较

生物活性

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

参考文献

溶解度 (25°C)

化学数据 Download Adavosertib (MK-1775) SDF

动物体内配方计算器 (澄清溶液)

计算器

摩尔浓度计算器

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

稀释计算器

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

连续稀释计算器方程

连续稀释

计算结果

分子量计算器

总分子量：g/mol

摩尔浓度计算器

临床试验信息 (data from https://clinicaltrials.gov, updated on 2021-05-17)

技术支持

常见问题及建议解决方法

Wee1 Signaling Pathway Map

相关Wee1产品