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 163 publications

Purity & Quality Control

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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 NXzaUWJ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;mNoRKSzVyPUGzMlIhyrFiMT6xJO69VQ>? NXLDclUxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW0OVg6PTRpPkK1OFU5QTV2PD;hQi=>
BxPC-3 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\pTVNKSzVyPUCuPEDDuSByLkCzJO69VQ>? NYTsWYpuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW0OVg6PTRpPkK1OFU5QTV2PD;hQi=>
CFPAC-1 NVPSRo9CT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{f1OWlEPTB;Mz6zJOKyKDBwMjFOwG0> M{j1SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NEW4PVU1Lz5{NUS1PFk2PDxxYU6=
HPAC NXn6[WhLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2HPcWlEPTB;MD61JOKyKDBwMEGg{txO MoLCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV2NUi5OVQoRjJ3NEW4PVU1RC:jPh?=
MIAPaCa-2 MnTZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\RTWM2OD1yLkWgxtEhOC5yNTFOwG0> M{XV[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NEW4PVU1Lz5{NUS1PFk2PDxxYU6=
PANC-1 NXHBTpVqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWLOSVF3UUN3ME2xNE43KMLzIEGuNUDPxE1? M3jn[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NEW4PVU1Lz5{NUS1PFk2PDxxYU6=
SK-N-BE (2) NUH6PFdYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2S0XmlEPTB;Mj605qCKyrIkgJmwMlMh|ryP NIDDWms9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUOwPFkyPid-MkWzNFg6OTZ:L3G+
SK-N-BE (2), PAN→MK MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmC3TWM2OD1{Nj625qCKyrIkgJm5MlYh|ryP MlXoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV|MEi5NVYoRjJ3M{C4PVE3RC:jPh?=
SK-N-BE (2), MK→PAN NX3lVGF2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;rPGlEPTB;Mj605qCKyrIkgJmwMlMh|ryP MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTNyOEmxOkc,OjV|MEi5NVY9N2F-
SK-N-AS MmPFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLrTWM2OD1yLkWw5qCKyrIkgJmwMlAzKM7:TR?= MlL2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV|MEi5NVYoRjJ3M{C4PVE3RC:jPh?=
SK-N-DZ Mo\jS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHWweYhKSzVyPUCuN|bjiIoEsfMAjVAvODFizszN NV7aWGYxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWzNFg6OTZpPkK1N|A5QTF4PD;hQi=>
SK-N-AS M{nySWFxd3C2b4Ppd{BCe3OjeR?= MX21NFAhdk1? MWS0PEBp NGTXZXhqdmS3Y3XzJINmdGxiYYDvdJRwe2m| M{f5fFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{C4PVE3Lz5{NUOwPFkyPjxxYU6=
SK-N-DZ M13tdmFxd3C2b4Ppd{BCe3OjeR?= M4HINlUxOCCwTR?= NIDPXIU1QCCq M3;1UIlv\HWlZYOgZ4VtdCCjcH;weI9{cXN? MlWyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV|MEi5NVYoRjJ3M{C4PVE3RC:jPh?=
THP-1 NUjlW2ZLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\kbIxEOTJ3L{K1NE82ODBibl2= MXq0PEBp NIj1elRqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NFHSdZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC4OFYyPCd-MkWwPFQ3OTR:L3G+
MV4-11 NIfEV2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEfxS|YyOjVxMkWwM|UxOCCwTR?= NVjRWm42PDhiaB?= NVW1[oN7cW6lcnXhd4V{KGOnbHyg[IVifGhiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? M3fjeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEi0OlE1Lz5{NUC4OFYyPDxxYU6=
U937 NH7nelVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHoO4IyOjVxMkWwM|UxOCCwTR?= M2TyVFQ5KGh? NGrveZJqdmO{ZXHz[ZMh[2WubDDk[YF1cCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M2DxOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEi0OlE1Lz5{NUC4OFYyPDxxYU6=
HL-60 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGmzZmwyOjVxMkWwM|UxOCCwTR?= MlvvOFghcA>? Mm\IbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> M370fVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MEi0OlE1Lz5{NUC4OFYyPDxxYU6=
OCI-AML3 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnJbJYyOjVxMkWwM|UxOCCwTR?= M4LaTlQ5KGh? MkTQbY5kemWjc3XzJINmdGxiZHXheIghcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NWfzNZNwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwPFQ3OTRpPkK1NFg1PjF2PD;hQi=>
MOLM-13 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTtNVI2NzJ3MD:1NFAhdk1? NFTZS2E1QCCq M2LvcYlv[3KnYYPld{Bk\WyuIHTlZZRpKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB6NE[xOEc,OjVyOES2NVQ9N2F-
CMK NGD3dZRE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MUCxNE0yODByMDDuUS=> NGnlPI04OiCq Mn\udoVlfWOnczDj[YxtKH[rYXzpZol1gSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NEL6XGM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEm2NlM{OSd-MkS5OlI{OzF:L3G+
CMY M1fIUGNmdGxiVnnhZoltcXS7IFHzd4F6 M1jBNVExNTFyMECwJI5O NWrsZVVQPzJiaB?= M{XPN5Jm\HWlZYOgZ4VtdCC4aXHsbYJqfHliaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? M2Ph[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OU[yN|MyLz5{NEm2NlM{OTxxYU6=
Dayo NHGy[ZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIG5Um1KSzVyPUG1NEBvVQ>? NXT2Um1[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2OlE6OTBpPkK0OlYyQTFyPD;hQi=>
UW228 NUDGTHl1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;CV2lEPTB;MkOyJI5O Moe5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NkG5NVAoRjJ2Nk[xPVExRC:jPh?=
IST-MES1 MVLD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NIjjbJoyPTBxMkWwJI5O Ml;vO|IhcA>? M37UVYVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? NFXPT289[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO2OVc5Oid-MkSzOlU4QDJ:L3G+
IST-MES2 MYXD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NEDhXVgyPTBxMkWwJI5O MV23NkBp MYDlcohidmOnczD0bIUh[2m|cHzheIlvKGO7dH;0c5hq[yCnZn\lZ5QhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NXfpVmtlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlU4QDJpPkK0N|Y2Pzh{PD;hQi=>
REN NVnZemlbS2WubDDWbYFjcWyrdImgRZN{[Xl? MV6xOVAwOjVyIH7N NIrRcW04OiCq Ml3r[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NVm0[o5RRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzOlU4QDJpPkK0N|Y2Pzh{PD;hQi=>
NCI-H2452 M3PzPGNmdGxiVnnhZoltcXS7IFHzd4F6 NUXjWos5OTVyL{K1NEBvVQ>? Mm\iO|IhcA>? M{n3eYVvcGGwY3XzJJRp\SClaYPwcIF1cW5iY4n0c5RwgGmlIHXm[oVkfCCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN4NUe4Nkc,OjR|NkW3PFI9N2F-
MSTO-211H M3vWOmNmdGxiVnnhZoltcXS7IFHzd4F6 MlTINVUxNzJ3MDDuUS=> MnPPO|IhcA>? NYLES|hQ\W6qYX7j[ZMhfGinIHPpd5Bt[XSrbjDjfZRwfG:6aXOg[YZn\WO2IHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ MmTXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NkW3PFIoRjJ2M{[1O|gzRC:jPh?=
NCI-H2052 MWTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NUjKPJNqOTVyL{K1NEBvVQ>? MWe3NkBp MkHZ[Y5p[W6lZYOgeIhmKGOrc4DsZZRqdiCleYTveI95cWNiZX\m[YN1KGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz MoW2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|NkW3PFIoRjJ2M{[1O|gzRC:jPh?=
WEE1 Mmm5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PTfWlEPTB;NT6yJI5O NHG0dJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[5PVY2PSd-MkO2PVk3PTV:L3G+
CDC2 NXi5[oQ1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLvSoRvUUN3MP-8olExODBibl2= NEe2boQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[5PVY2PSd-MkO2PVk3PTV:L3G+
CDK7 MnHsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|Ux97zgMUCwNEBvVQ>? NX3uZ|BIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2PVk3PTVpPkKzOlk6PjV3PD;hQi=>
MYT1 M2r5dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTV|MDDuUS=> NWnQTnhqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2PVk3PTVpPkKzOlk6PjV3PD;hQi=>
T98G  MmX6RZBweHSxc3nzJGF{e2G7 M{XNdlExOC9{NUCgcm0> Mlf3OkBp MWHlcohidmOnczDyZYRq[XSrb36tbY5lfWOnZDDj[YxtKGurbHzpcoc> NXXiZldrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5PVI4QTNpPkKxPVkzPzl|PD;hQi=>
A549 NEfKdpBCeG:ydH;zbZMhSXO|YYm= MVuyNFAhdk1? M17XUVEhcA>? Ml;udoFlcW:|ZX7zbZRqgmW|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK= MkHtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF5OUmwN|MoRjJzN{m5NFM{RC:jPh?=
H460 NUTKVW04SXCxcITvd4l{KEG|c3H5 MnrPNlAxKG6P M1zMN|EhcA>? NYK2WFh6emGmaX;z[Y5{cXSrenXzJG5US0yFIHPlcIx{KGmwIHGgdFU{NWSncHXu[IVvfCCvYX7u[ZI> M4LMTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzN{m5NFM{Lz5{MUe5PVA{OzxxYU6=
H1299 NYH4eXM3SXCxcITvd4l{KEG|c3H5 NXv3U2pVOjByIH7N MmW4NUBp MonRdoFlcW:|ZX7zbZRqgmW|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK= M2XaclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzN{m5NFM{Lz5{MUe5PVA{OzxxYU6=
Calu-6  NGri[FhCeG:ydH;zbZMhSXO|YYm= NEDCeFAzODBibl2= NV\YbYhoOSCq MlHPdoFlcW:|ZX7zbZRqgmW|IF7TR2xEKGOnbHzzJIlvKGFicEWzMYRmeGWwZHXueEBu[W6wZYK= MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTd7OUCzN{c,OjF5OUmwN|M9N2F-
WiDr NWLpSYZYU2mwYYPlJGF{e2G7cx?= M1jhRVExNTFyMECwJI5O Mn3iPEBp MorQbY5pcWKrdIOgdIhwe3Cqb4L5cIF1cW:wIH;mJGNFSzJiYYSgWJlzOTVid3n0bEBidiCHQ{WwxsB3[Wy3ZTDv[kA5PSCwbX;sM2wheHKndILlZZRm\CC5aYToJIdmdWOrdHHibY5m MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTh6N{W0OUc,OTl6OEe1OFU9N2F-
Function assay MV3FfJBqOjl|Rh?= NUnaN4N1SmmwZHnu[{Bi\m[rbnn0fUB1dyC{ZXPvcYJqdmGwdDDoeY1idiCodXzsMYxmdme2aDDOMZRmem2rbnHsJGhqezhvdHHn[4VlKFenZUGgLFEhfG9iNkS2JJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iaIXtZY4hTXiyaUK5N2Yh[2WubIOgZZN{\XO|ZXSgZZMh\GW|c3;jbYF1cW:wIHPvcpN1[W62IHL5JJF2[W62aYTheIl3\SC{ZXHsMZRqdWViUFPSJI1mfGixZDygT4QhRSByLkCwN|Ih|ryPLh?= MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd7Mke2NEc,Ojh5OUK3OlA9N2F-
Function assay M{XWTmV5eGl{OUPG NHTpfoJDcW6maX7nJIFn\mmwaYT5JJRwKHKnY3;tZolv[W62IHj1cYFvKG[3bHytcIVv\3SqIF6teIVzdWmwYXygTIl{QC22YXfn[YQhX2WnMjCoNUB1dyB3NkegdoV{cWS3ZYOpJIV5eHKnc4Pl[EBqdiCqdX3hckBGgHCrMkmzSkBk\WyuczDhd5Nme3OnZDDhd{Bl\XO|b3PpZZRqd25iY3;ud5RidnRiYomgdZVidnSrdHH0bZZmKHKnYXyteIlu\SCSQ2KgcYV1cG:mLDDL[EA:KDBwMECzPUDPxE1w NXvGWYlzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3PVI4PjBpPkK4O|kzPzZyPD;hQi=>
Antiproliferative assay NXHpXoVuVUSDLV3CMVI{OQ>? M3zkTFczKGi{cx?= M3PrdWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVTBMW1DNTJ|MTDj[YxteyCvZXHzeZJm\CCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUKudXWgZZN{[XluIFnDOVAhRSByLkK2JO69VS5? MoHOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5OUK3OlAoRjJ6N{myO|YxRC:jPh?=
Antiproliferative assay NXuzUmF5UEWNMkmzWC=> M1LtO|czKGi{cx?= MmTIRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDISWszQTOWIHPlcIx{KG2nYYP1doVlKGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuSmy3ZTDhd5NigSxiSVO1NEA:KDBwMkmg{txONg>? M2HNZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6N{myO|YxLz5{OEe5Nlc3ODxxYU6=
Antiproliferative assay MY\NUVFU MlHTO|IhcHK| M33xT2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTV2xV{Bk\WyuczDt[YF{fXKnZDDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVLseYUh[XO|YYmsJGlEPTBiPTCwMlMyKM7:TT6= MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd7Mke2NEc,Ojh5OUK3OlA9N2F-
Function assay M4ToOmhGUzJ7Mx?= M1HqRVEhcHJ? MnPlTY5pcWKrdHnvckBw\iCqdX3hckBnfWyuIHzlcod1cCCSS13ZWFEh\XiycnXzd4VlKGmwIFjFT|I6OyClZXzsd{B2e2mwZzDFSnMhMDJ2NzD0c{AzPTlicnXzbYR2\XNrIHHzJJN2[nO2cnH0[UBi\nSncjCxJIhzKGK7IH\seY9z\XOlZX7j[UBxd2yjcnn6ZZRqd25iaX3teY5w[XOjeTygT4khRSByLkS3JO69VS5? M2\Ub|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUSxNVk{Lz5{OUm0NVE6OzxxYU6=
Function assay M3vyb2hGUzJ7Mx?= MniwNUBpeg>? NXfHcHlUUW6qaXLpeIlwdiCxZjDoeY1idiCodXzsJIxmdme2aDDQT21[XDFiZYjwdoV{e2WmIHnuJGhGUzJ7MzDj[YxteyC3c3nu[{BGTlNiKEK0O{B1dyB{NUmgdoV{cWS3ZYOpJIF{KHO3YoP0doF1\SCjZoTldkAyKGi{IHL5JIZtfW:{ZYPj[Y5k\SCyb3zhdol7[XSrb36gbY1ufW6xYYPhfUwhUUN3MDC9JFQvQTRizszNMi=> NFXoWnE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUm0NVE6Oyd-Mkm5OFEyQTN:L3G+
Function assay M2PYem1FSS2PQj2yN|E> NYDvdpAyOC5zIITvJFExKHWP M4T0OVYhcHK| M2DGRWlvcGmkaYTpc44hd2ZiV3XlNUBqdiCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIFPET|EheGixc4Doc5J6dGG2aX;uJIF1KFS7cjCxOUBifCByLkGgeI8hOTBidV2gZYZ1\XJiNjDodpMh[nliV3XzeIVzdiCkbH;0JI1mfGixZB?= MljXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5OUK3OlAoRjJ6N{myO|YxRC:jPh?=
Function assay MYjISWszQTOW M{TQeFAvOSC2bzCxNEB2VQ>? NIK2TWw3KGi{cx?= M3nDNWlvcGmkaYTpc44hd2ZiV3XlNUBqdiCKRVuyPVNVKGOnbHzzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIFPET|EheGixc4Doc5J6dGG2aX;uJIF1KFS7ckG1JIF1KDBwMTD0c{AyOCC3TTDh[pRmeiB4IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m NYjMcnV3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3PVI4PjBpPkK4O|kzPzZyPD;hQi=>
Function assay NEjPfFFJTUt{OUPU M1foUFAvOSC2bzCxNEB2VQ>? NFjrbms3KGi{cx?= M{TaWGlvcGmkaYTpc44hd2ZiUFzLNUBqdiCKRVuyPVNVKGOnbHzzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIGTDWHAheGixc4Doc5J6dGG2aX;uJIF1KDBwMTD0c{AyOCC3TTDh[pRmeiB4IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd7Mke2NEc,Ojh5OUK3OlA9N2F-
Function assay NWHhRndnVUSDLV3CMVI{ M4\BbVAvOSC2bzCxNEB2VQ>? MlrHOkBpenN? MXfJcohq[mm2aX;uJI9nKFCOS{GgbY4hcHWvYX6gUWRCNU2ELUKzJINmdGy|IHHzd4V{e2WmIHHzJIRm[3KnYYPlJIlvKFSFVGCgdIhwe3Cqb4L5cIF1cW:wIHH0JFAvOSC2bzCxNEB2VSCjZoTldkA3KGi{czDifUBY\XO2ZYLuJIJtd3RibXX0bI9l MkHMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5OUK3OlAoRjJ6N{myO|YxRC:jPh?=
qHTS assay MY\UR|Mz M2e4WpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCWQ{OyJINmdGy| NWTBUGp7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay MWHVMVIhV1N? MUnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy| Mn3mQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay NGnvfVNCPjd| NE\sNHJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?= Mk\WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay NWLOfoE3TEGRWR?= NWnwS|VReUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFTBU3kh[2WubIO= NGjQeZo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
qHTS assay NX;tR|dDW2Gxcz2y MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW2Gxcz2yJINmdGy| NYW0eJk{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay NWHaRoI3SlRvM{e= M{DWdJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2zO{Bk\Wyucx?= NX3MRXRiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay NUf6PW95WkR? M{i5XZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCURDDj[Yxtew>? MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay MmPMV2suVi2VSB?= NH7J[HlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1UUCClZXzsdy=> M2ezdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay MUXCWE0yOg>? MVnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN? NGD2V|M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
qHTS assay M4PBe25DOTZ2Mx?= Mn\tdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?= MlzrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay NV\H[VM4V0iVLUWw Moj4dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE:KUz21NEBk\Wyucx?= M1LoOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay M2jRSmJVNTF{ M4PnV5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTF{IHPlcIx{ MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay MoTtSGFQYQ>? NWXy[4l5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>? NFOyR4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
qHTS assay NHrxPXlUUy2QLWPI NHf2T|FyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLWPIJINmdGy| NV;NO5BmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay M3PHZ3JpPDF? MYfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh2MTDj[Yxtew>? NYDIbGg{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay NGXYSZVCPjd| MoL0dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgRVY4OyClZXzsd{k> NWXBOm12RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay MWfNS{A3OyBqNj3US{BTMQ>? NIPEenByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBOTyB4MzCoOk1VTyCUKTDj[Yxtew>? MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay MnjSWU0zKE:V NF;xWHVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBWNTJiT2OgZ4VtdHN? MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay MkXZU2hUNTVy M2rvZZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJG9JWy13MDDj[Yxtew>? MnTJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay MWDSbFQy MULxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFQyKGOnbHzz M{[1SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay MVnSSC=> NIP0OYxyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBTTCClZXzsdy=> M2q1TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay NYLlS4N{W0pvR1LNNi=> MVHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?= NIjmUpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
qHTS assay NYfpR2ZCW0tvTj3NRy=> MXHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?= Mn\jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
qHTS assay NYD6T5VOVkJvRVLjNS=> NV\x[XlZeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF7CMWVD[zFiY3XscJM> M3XH[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
qHTS assay M2OwWWxCVi13 M4PzbJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCOQV6tOUBk\Wyucx?= MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay M{\2U3JpOTh? NXW0[oZUeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGLoNVgh[2WubIO= MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
qHTS assay MYDTTk1ISk1{ MVjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTTk1ISk1{IHPlcIx{ NXHmbZpwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
qHTS assay MmSyV4Fwey1{ MYTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTZY9{NTJiY3XscJM> NXfCRmMzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
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.

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

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

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
NCT03012477 Completed Drug: Cisplatin|Drug: AZD1775 Triple-negative Metastatic Breast Cancer Dana-Farber Cancer Institute|AstraZeneca January 18 2017 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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
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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.

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