Adavosertib (MK-1775)

Catalog No.S1525 Synonyms: AZD1775

For research use only.

Adavosertib (MK-1775, AZD1775) is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM in a cell-free assay; hinders G2 DNA damage checkpoint. Phase 2.

Adavosertib (MK-1775) Chemical Structure

CAS No. 955365-80-7

Selleck's Adavosertib (MK-1775) has been cited by 159 publications

Purity & Quality Control

Choose Selective Wee1 Inhibitors

Other Wee1 Products

Biological Activity

Description Adavosertib (MK-1775, AZD1775) is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM in a cell-free assay; hinders G2 DNA damage checkpoint. Phase 2.
Features The first reported Wee1 inhibitor.
Targets
Wee1 [1]
(Cell-free assay)
5.2 nM
In vitro

MK-1775 inhibits Wee1 kinase in an ATP-competitive manner. Compared to Wee1, MK-1775 displays 2- to 3-fold less potency against Yes with IC50 of 14 nM, 10-fold less potency against seven other kinases with >80% inhibition at 1 μM, and >100-fold selectivity over human Myt 1, another kinase that inhibits cyclin-dependent kinase 1 (CDC2) by phosphorylation at an alternative site (Thr14). By abrogating the DNA damage checkpoint via blockade of Wee1 activity in WiDr cells bearing mutated p53, MK-1775 treatment inhibits the basal phosphorylation of CDC2 at Tyr15 (CDC2Y15) with EC50 of 49 nM, and suppresses gemcitabine-, carboplatin- or cisplatin-induced phosphorylation of CDC2 and cell cycle arrest in a dose-dependent manner, with EC50 of 82 nM and 81 nM, 180 nM and 163 nM, as well as 159 nM and 160 nM, respectively. MK-1775 treatment alone at 30-100 nM has no significant antiproliferative effect in WiDr and H1299 cells, whereas MK-1775 at 300 nM, sufficient to inhibit Wee1 by >80%, displays moderate but significant antiproliferative effects by 34.1% in WiDr cells and 28.4% in H1299 cells. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
ASPC-1 NVnzOop{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF3vXJhKSzVyPUGzMlIhyrFiMT6xJO69VQ>? M2PiRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NEW4PVU1Lz5{NUS1PFk2PDxxYU6=
BxPC-3 NVfJRnVpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1OzT2lEPTB;MD64JOKyKDBwMEOg{txO NIT4dmE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUS1PFk2PCd-MkW0OVg6PTR:L3G+
CFPAC-1 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPaTWM2OD1|LkOgxtEhOC5{IN88US=> NXLTeohJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW0OVg6PTRpPkK1OFU5QTV2PD;hQi=>
HPAC MofwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHaSJZwUUN3ME2wMlUhyrFiMD6wNUDPxE1? NYrRUXhVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW0OVg6PTRpPkK1OFU5QTV2PD;hQi=>
MIAPaCa-2 NXzt[pJRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXLJR|UxRTBwNTFCtUAxNjB3IN88US=> MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTR3OEm1OEc,OjV2NUi5OVQ9N2F-
PANC-1 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHv4TVNKSzVyPUGwMlYhyrFiMT6xJO69VQ>? M4jJNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NEW4PVU1Lz5{NUS1PFk2PDxxYU6=
SK-N-BE (2) NXmzc25tT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTJwNPMAjeKy6oDLMD6zJO69VQ>? M4TUZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{C4PVE3Lz5{NUOwPFkyPjxxYU6=
SK-N-BE (2), PAN→MK NGLLbnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmL6TWM2OD1{Nj625qCKyrIkgJm5MlYh|ryP NFjPd5k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPFkyPid-MkWzNFg6OTZ:L3G+
SK-N-BE (2), MK→PAN M4DwWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYLJR|UxRTJwNPMAjeKy6oDLMD6zJO69VQ>? NFXSdYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPFkyPid-MkWzNFg6OTZ:L3G+
SK-N-AS MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPMTWM2OD1yLkWw5qCKyrIkgJmwMlAzKM7:TR?= NFnWZ2w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPFkyPid-MkWzNFg6OTZ:L3G+
SK-N-DZ NHPZcnJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3q3ZWlEPTB;MD6zOwKBkcLz4pEJNE4xOSEQvF2= MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTNyOEmxOkc,OjV|MEi5NVY9N2F-
SK-N-AS M{LyWWFxd3C2b4Ppd{BCe3OjeR?= NGLmOok2ODBibl2= NY\VWlJsPDhiaB?= M1LyNolv\HWlZYOgZ4VtdCCjcH;weI9{cXN? NGrCfoY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPFkyPid-MkWzNFg6OTZ:L3G+
SK-N-DZ NEDHOWxCeG:ydH;zbZMhSXO|YYm= M4THeVUxOCCwTR?= M{XEU|Q5KGh? M4Tieolv\HWlZYOgZ4VtdCCjcH;weI9{cXN? M4TMeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{C4PVE3Lz5{NUOwPFkyPjxxYU6=
THP-1 NIjy[VNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXuxNlUwOjVyL{WwNEBvVQ>? MWG0PEBp NFjrelVqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NVr3XJpPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwPFQ3OTRpPkK1NFg1PjF2PD;hQi=>
MV4-11 NEjoUFRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDsNVI2NzJ3MD:1NFAhdk1? MUe0PEBp MkjJbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB6NE[xOEc,OjVyOES2NVQ9N2F-
U937 M2PXOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX:xNlUwOjVyL{WwNEBvVQ>? NEHWNpM1QCCq M4rm[Ilv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB6NE[xOEc,OjVyOES2NVQ9N2F-
HL-60 NXXWN2dxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfaNVI2NzJ3MD:1NFAhdk1? M2DIe|Q5KGh? MX\pcoNz\WG|ZYOgZ4VtdCCmZXH0bEBqdiCjIHPvcoNmdnS{YYTpc44u\GWyZX7k[Y51KG2jbn7ldi=> MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB6NE[xOEc,OjVyOES2NVQ9N2F-
OCI-AML3 NGXKOZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1v1blEzPS9{NUCvOVAxKG6P M4e0TlQ5KGh? NVS2dIFicW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB6NE[xOEc,OjVyOES2NVQ9N2F-
MOLM-13 MkL5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;OSGJvOTJ3L{K1NE82ODBibl2= M3K1VVQ5KGh? Ml70bY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> M2K2d|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEi0OlE1Lz5{NUC4OFYyPDxxYU6=
CMK Mo\jR4VtdCCYaXHibYxqfHliQYPzZZk> MX6xNE0yODByMDDuUS=> MoPaO|IhcA>? NWe4U2UzemWmdXPld{Bk\WyuII\pZYxq[mm2eTDpckBiKGOxbnPlcpRz[XSrb36t[IVx\W6mZX70JI1idm6nch?= MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl4MkOzNUc,OjR7NkKzN|E9N2F-
CMY NU\zPY5IS2WubDDWbYFjcWyrdImgRZN{[Xl? M4jKOFExNTFyMECwJI5O NX;lRnN6PzJiaB?= MmXUdoVlfWOnczDj[YxtKH[rYXzpZol1gSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl4MkOzNUc,OjR7NkKzN|E9N2F-
Dayo NWXETIx7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfrTXlKSzVyPUG1NEBvVQ>? NHjsdm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[2NVkyOCd-MkS2OlE6OTB:L3G+
UW228 M4XZRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\ITWM2OD1{M{Kgcm0> NX35S3NlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2OlE6OTBpPkK0OlYyQTFyPD;hQi=>
IST-MES1 M2f4bGNmdGxiVnnhZoltcXS7IFHzd4F6 MnLDNVUxNzJ3MDDuUS=> NHrreIs4OiCq NF6xR3VmdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? MnH2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NkW3PFIoRjJ2M{[1O|gzRC:jPh?=
IST-MES2 NVnwSFlDS2WubDDWbYFjcWyrdImgRZN{[Xl? MXqxOVAwOjVyIH7N NYPVXXUxPzJiaB?= NIrofJBmdmijbnPld{B1cGViY3nzdIxifGmwIHP5eI91d3irYzDl[oZm[3RiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? NXf1V2hHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlU4QDJpPkK0N|Y2Pzh{PD;hQi=>
REN M{HCXGNmdGxiVnnhZoltcXS7IFHzd4F6 M4rsdlE2OC9{NUCgcm0> M{njXVczKGh? MkDG[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MnP3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NkW3PFIoRjJ2M{[1O|gzRC:jPh?=
NCI-H2452 NFzlOZdE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MnzkNVUxNzJ3MDDuUS=> NHKxW3I4OiCq NYrFO|Zm\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN4NUe4Nkc,OjR|NkW3PFI9N2F-
MSTO-211H MWrD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NUPxfXRtOTVyL{K1NEBvVQ>? M1\lXlczKGh? Mmmx[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NYWxepByRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlU4QDJpPkK0N|Y2Pzh{PD;hQi=>
NCI-H2052 NGDFSI1E\WyuIG\pZYJqdGm2eTDBd5NigQ>? MV[xOVAwOjVyIH7N NX71No5OPzJiaB?= MkX6[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NYnOcldDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlU4QDJpPkK0N|Y2Pzh{PD;hQi=>
WEE1 MlywS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlzVTWM2OD13LkKgcm0> M4L1NFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|Nkm5OlU2Lz5{M{[5PVY2PTxxYU6=
CDC2 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXPJR|Ux97zgMUCwNEBvVQ>? MmO4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4OUm2OVUoRjJ|Nkm5OlU2RC:jPh?=
CDK7 M3Xhbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfiTZNKSzVy78{eNVAxOCCwTR?= MnfKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4OUm2OVUoRjJ|Nkm5OlU2RC:jPh?=
MYT1 NX;XelVLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnvDTWM2OD13M{Cgcm0> M2jqTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|Nkm5OlU2Lz5{M{[5PVY2PTxxYU6=
T98G  NX3YRnJnSXCxcITvd4l{KEG|c3H5 MWexNFAwOjVyIH7N NFfjS2w3KGh? MkCx[Y5p[W6lZYOgdoFlcWG2aX;uMYlv\HWlZXSgZ4VtdCCtaXzsbY5o NGPRR2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm5Nlc6Oyd-MkG5PVI4QTN:L3G+
A549 MXTBdI9xfG:|aYOgRZN{[Xl? NWXNUXN1OjByIH7N MXOxJIg> M4fa[ZJi\Gmxc3Xud4l1cXqnczDOV2NNSyClZXzsd{BqdiCjIIC1N{1l\XCnbnTlcpQhdWGwbnXy MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTd7OUCzN{c,OjF5OUmwN|M9N2F-
H460 NV7hWndNSXCxcITvd4l{KEG|c3H5 MkK4NlAxKG6P MoPhNUBp MV7yZYRqd3OnboPpeIl7\XNiTmPDUGMh[2WubIOgbY4h[SCyNUOt[IVx\W6mZX70JI1idm6nch?= M4XqRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzN{m5NFM{Lz5{MUe5PVA{OzxxYU6=
H1299 NFPaPYhCeG:ydH;zbZMhSXO|YYm= MX6yNFAhdk1? NYLXeY5qOSCq MkHtdoFlcW:|ZX7zbZRqgmW|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK= MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTd7OUCzN{c,OjF5OUmwN|M9N2F-
Calu-6  NXm2U5h7SXCxcITvd4l{KEG|c3H5 NXfkfmlOOjByIH7N NVfkT25bOSCq NEWyUXRz[WSrb4PlcpNqfGm8ZYOgUnNEVENiY3XscJMhcW5iYTDwOVMu\GWyZX7k[Y51KG2jbn7ldi=> Mny4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF5OUmwN|MoRjJzN{m5NFM{RC:jPh?=
WiDr MoHOT4lv[XOnIFHzd4F6ew>? MWmxNE0yODByMDDuUS=> NIjLNY05KGh? MX3pcohq[mm2czDwbI9{eGixconsZZRqd25ib3[gR2REOiCjdDDUfZIyPSC5aYToJIFvKEWFNUFCpJZidHWnIH;mJFg2KG6vb3yvUEBxemW2cnXheIVlKHerdHig[4Vu[2m2YXLpcoU> MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTh6N{W0OUc,OTl6OEe1OFU9N2F-
Function assay MkXpSZhxcTJ7M1[= MX7CbY5lcW6pIHHm[olvcXS7IITvJJJm[2:vYnnuZY51KGi3bXHuJIZ2dGxvbHXu[5RpKE5vdHXycYlv[WxiSHnzPE11[WepZXSgW4VmOSBqMTD0c{A3PDZicnXzbYR2\XNrIHX4dJJme3OnZDDpckBpfW2jbjDFfJBqOjl|RjDj[YxteyCjc4Pld5Nm\CCjczDk[ZN{d2OrYYTpc44h[2:wc4ThcpQh[nlicYXhcpRqfGG2aY\lJJJm[WxvdHnt[UBRS1JibXX0bI9lNCCNZDC9JFAvODB|MjFOwG0v NGHQdYQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEe5Nlc3OCd-Mki3PVI4PjB:L3G+
Function assay MY\FfJBqOjl|Rh?= MVfCbY5lcW6pIHHm[olvcXS7IITvJJJm[2:vYnnuZY51KGi3bXHuJIZ2dGxvbHXu[5RpKE5vdHXycYlv[WxiSHnzPE11[WepZXSgW4VmOiBqMTD0c{A2PjdicnXzbYR2\XNrIHX4dJJme3OnZDDpckBpfW2jbjDFfJBqOjl|RjDj[YxteyCjc4Pld5Nm\CCjczDk[ZN{d2OrYYTpc44h[2:wc4ThcpQh[nlicYXhcpRqfGG2aY\lJJJm[WxvdHnt[UBRS1JibXX0bI9lNCCNZDC9JFAvODB|OTFOwG0v MlnCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5OUK3OlAoRjJ6N{myO|YxRC:jPh?=
Antiproliferative assay MorYUWRCNU2ELUKzNS=> M{DGZVczKGi{cx?= NYXwPY44SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvMkOxJINmdGy|IH3lZZN2emWmIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvQnz1[UBie3OjeTygTWM2OCB;IECuNlYh|ryPLh?= NYXVeVRGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3PVI4PjBpPkK4O|kzPzZyPD;hQi=>
Antiproliferative assay MnXzTGVMOjl|VB?= MX23NkBpenN? NIrGdXZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JGhGUzJ7M2SgZ4VtdHNibXXhd5Vz\WRiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2EbIXlJIF{e2G7LDDJR|UxKD1iMD6yPUDPxE1w M1q4TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6N{myO|YxLz5{OEe5Nlc3ODxxYU6=
Antiproliferative assay NFztTpNOVTGV MoXOO|IhcHK| NHqxRYZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3NNXMh[2WubIOgcYVie3W{ZXSgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3CcJVmKGG|c3H5MEBKSzVyIE2gNE4{OSEQvF2u Mn;0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5OUK3OlAoRjJ6N{myO|YxRC:jPh?=
Function assay NX3JOJVYUEWNMkmz M2q4ZVEhcHJ? NFrXVJhKdmirYnn0bY9vKG:oIHj1cYFvKG[3bHygcIVv\3SqIGDLUXlVOSCneIDy[ZN{\WRiaX6gTGVMOjl|IHPlcIx{KHW|aX7nJGVHWyBqMkS3JJRwKDJ3OTDy[ZNq\HWnczmgZZMhe3Wkc4TyZZRmKGGodHXyJFEhcHJiYomg[ox2d3Knc3PlcoNmKHCxbHHybZpifGmxbjDpcY12dm:jc3H5MEBMcSB;IECuOFch|ryPLh?= MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MUG5N{c,Ojl7NEGxPVM9N2F-
Function assay NHTpOHRJTUt{OUO= NH7FXI4yKGi{ NVnUOldFUW6qaXLpeIlwdiCxZjDoeY1idiCodXzsJIxmdme2aDDQT21[XDFiZYjwdoV{e2WmIHnuJGhGUzJ7MzDj[YxteyC3c3nu[{BGTlNiKEK0O{B1dyB{NUmgdoV{cWS3ZYOpJIF{KHO3YoP0doF1\SCjZoTldkAyKGi{IHL5JIZtfW:{ZYPj[Y5k\SCyb3zhdol7[XSrb36gbY1ufW6xYYPhfUwhUUN3MDC9JFQvQTRizszNMi=> MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MUG5N{c,Ojl7NEGxPVM9N2F-
Function assay MkHlUWRCNU2ELUKzNS=> NIrJ[IcxNjFidH:gNVAhfU1? NUfqeIdxPiCqcoO= M{XwZmlvcGmkaYTpc44hd2ZiV3XlNUBqdiCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIFPET|EheGixc4Doc5J6dGG2aX;uJIF1KFS7cjCxOUBifCByLkGgeI8hOTBidV2gZYZ1\XJiNjDodpMh[nliV3XzeIVzdiCkbH;0JI1mfGixZB?= MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd7Mke2NEc,Ojh5OUK3OlA9N2F-
Function assay NYHDeHNWUEWNMkmzWC=> NV3pSml6OC5zIITvJFExKHWP Mn:wOkBpenN? M1PPNmlvcGmkaYTpc44hd2ZiV3XlNUBqdiCKRVuyPVNVKGOnbHzzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIFPET|EheGixc4Doc5J6dGG2aX;uJIF1KFS7ckG1JIF1KDBwMTD0c{AyOCC3TTDh[pRmeiB4IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd7Mke2NEc,Ojh5OUK3OlA9N2F-
Function assay MUnISWszQTOW NXnHbIFLOC5zIITvJFExKHWP MmPFOkBpenN? NEjMTohKdmirYnn0bY9vKG:oIGDMT|EhcW5iSFXLNlk{XCClZXzsd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjDUR3RRKHCqb4PwbI9zgWyjdHnvckBifCByLkGgeI8hOTBidV2gZYZ1\XJiNjDodpMh[nliV3XzeIVzdiCkbH;0JI1mfGixZB?= NUfpO2d3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3PVI4PjBpPkK4O|kzPzZyPD;hQi=>
Function assay NEHPd21OTEFvTVKtNlM> NXTXZ3A{OC5zIITvJFExKHWP NGHQT|g3KGi{cx?= MnvGTY5pcWKrdHnvckBw\iCSTFuxJIlvKGi3bXHuJG1FSS2PQj2yN{Bk\WyuczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiCWQ2TQJJBpd3OyaH;yfYxifGmxbjDheEAxNjFidH:gNVAhfU1iYX\0[ZIhPiCqcoOgZpkhX2W|dHXyckBjdG:2IH3leIhw\A>? NXPpWFJnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3PVI4PjBpPkK4O|kzPzZyPD;hQi=>
qHTS assay NILRNndVSzN{ M3OwPJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCWQ{OyJINmdGy| M3;ZeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay MknIWU0zKE:V NH;RZ5VyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiVT2yJG9UKGOnbHzz NEPTUow9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
qHTS assay MkHaRVY4Ow>? MoO0dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEF4N{OgZ4VtdHN? NXjXelBLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay MXfERW9[ NF62clNyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?= M1nWNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay NGPDb4ZU[W:|LUK= NV3tZpNreUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=> MlK0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay NGftcWdDXC1|Nx?= M1fnPZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2zO{Bk\Wyucx?= NGf4OYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
qHTS assay NU[0N2ZCWkR? M1uxUZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCURDDj[Yxtew>? MmjZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay NX\tZmZwW0tvTj3TTC=> NEDmZVdyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1UUCClZXzsdy=> MnLBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay MVzCWE0yOg>? MljrdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy| MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay MXvORlE3PDN? MXTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJzNkSzJINmdGy| NVvZS|YxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay MVLPTHMuPTB? NGjBS3JyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiT1jTMVUxKGOnbHzz MorGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay NEPhcnpDXC1zMh?= M3Xac5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTF{IHPlcIx{ M4nmU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay NUn4enhxTEGRWR?= MUPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDERW9[KGOnbHzz NGXVfoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
qHTS assay NE[3RYhUUy2QLWPI NHrOO|ZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLWPIJINmdGy| MkXmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay MWPSbFQy NGTv[YpyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUni0NUBk\Wyucx?= M1Xnb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay M2LoeGE3PzN? NVTBRpRkeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhSTZ5MzDj[Yxteyl? MkTvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay NVH6c2JOVUdiNkOgLFYuXEdiUjm= NI\kPJZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBOTyB4MzCoOk1VTyCUKTDj[Yxtew>? M2\YSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay NIfKWGVWNTJiT2O= NFzJRW9yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBWNTJiT2OgZ4VtdHN? M2fWNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay NUDuU|l6V0iVLUWw NX3BfGZ7eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy| MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay M1L4PHJpPDF? NYPFSFJxeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhWmh2MTDj[Yxtew>? M1jNe|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay MoLBVmQ> MmjidWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVmQh[2WubIO= MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay MlrkV2ouT0KPMh?= NGO4fmhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1qtS2JOOiClZXzsdy=> Mo\NQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay M3rNb3NMNU5vTVO= NYrVT2c6eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM> M2nke|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay NF7hS|dPSi2HQnOx M4L0NJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQj3FRoMyKGOnbHzz MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay MX7MRW4uPQ>? NVKz[VVPeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz M4\zTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay MXrSbFE5 MlvpdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqMUigZ4VtdHN? MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay NHfTT3BUUi2JQl2y M3zLRpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNLNUeETUKgZ4VtdHN? NUXRb5dKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay MVLTZY9{NTJ? MVTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTZY9{NTJiY3XscJM> MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Assay
Methods Test Index PMID
Western blot p-Cdk1(Y15) / Cdk1 ; p-KAP1(S824) / p-Chk2(T68) / p-Chk1(S345) ; PARP / CF-PARP / pH3(S10) / p-CDC25c(S216) / p-CDK2(Y15) ; WEE1 25609063 25458954 27616351
Immunofluorescence tubulin / p-HH3(S10) ; γH2AX ; Cleaved caspase-3 / pH3 30755439 25609063 27616351
Growth inhibition assay Cell viability ; IC50 25458954 25084614
In vivo MK-1775 treatment alone at ~20 mg/kg displays minimal antitumor effects against WiDr xenografts in rats with T/C of 69% at day 3. Antitumor efficacy by MK-1775 alone in the nude rat HeLa-luc and TOV21G-shp53 xenograft models is also moderate. [1]

Protocol (from reference)

Kinase Assay:

[1]

  • In vitro kinase assays:

    Recombinant human Wee1 is used. Kinase reaction is conducted with 10 μM ATP, 1.0 μCi of [γ-33P]ATP, and 2.5 μg of poly(Lys, Tyr) as a substrate in the presence of increasing concentrations of MK-1775 at 30°C for 30 minutes. Radioactivity incorporated into the substrate is trapped on MultiScreen-PH plates and is counted on a liquid scintillation counter.

Cell Research:

[1]

  • Cell lines: WiDr, NCI-H1299, TOV21G, and HeLa
  • Concentrations: Dissolved in DMSO, final concentrations ~10 μM
  • Incubation Time: 24 hours
  • Method:

    Cells are treated with or without gemcitabine for 24 hours, then with MK-1775 for an additional 24 hours. Cell viability is determined with a WST-8 kit using SpectraMax. Cellular caspase-3/7 activities are determined with a Caspase-3/7 Glo kit.

  • (Only for Reference)
Animal Research:

[1]

  • Animal Models: Immunodeficient nude rats (F344/NJcl-rnu) bearing WiDr, HeLa-luc, or TOV21G-shp53 tumors
  • Dosages: ~20 mg/kg/day
  • Administration: Orally
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 80 mg/mL
(159.8 mM)
Water 0.0001 mg/mL
(0.0 mM)
Ethanol ''10 mg/mL warmed

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 500.6
Formula

C27H32N8O2

CAS No. 955365-80-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)(C1=NC(=CC=C1)N2C3=NC(=NC=C3C(=O)N2CC=C)NC4=CC=C(C=C4)N5CCN(CC5)C)O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

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

(data from https://clinicaltrials.gov, updated on 2021-09-06)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.

Frequently Asked Questions

Question 1:
How to prepare MK1775 methylcellulose solution? and how to prepare methylcellulose itself? Once make the MK1775 methylcellulose solution, how should i keep it?

Answer:
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.

Tags: buy Adavosertib (MK-1775) | Adavosertib (MK-1775) supplier | purchase Adavosertib (MK-1775) | Adavosertib (MK-1775) cost | Adavosertib (MK-1775) manufacturer | order Adavosertib (MK-1775) | Adavosertib (MK-1775) distributor