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Capivasertib (AZD5363)

Name: Capivasertib (AZD5363)
Brand: Selleck Chemicals
SKU: S8019
Rating: 5 (98 reviews)

Catalog No.S8019

For research use only.

Capivasertib (AZD5363) potently inhibits all isoforms of Akt(Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM in cell-free assays, similar to P70S6K/PKA and lower activity towards ROCK1/2. Phase 2.

Capivasertib (AZD5363) Chemical Structure

CAS No. 1143532-39-1

Selleck's Capivasertib (AZD5363) has been cited by 98 publications

Purity & Quality Control

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Akt Signaling Pathway Map

Biological Activity

Description

Features

Moderate preclinical tolerability, and PD characteristics of an AKT inhibitor. Distinct profile from other AKT inhibitors in clinical development.

Targets

Akt1 ^[1] (Cell-free assay)	Akt2 ^[1] (Cell-free assay)	Akt3 ^[1] (Cell-free assay)	ROCK2 ^[1] (Cell-free assay)
3 nM	8 nM	8 nM	56 nM

In vitro

AZD5363 is a potent Akt inhibitor with IC50 of 3 nM, 8 nM and 8 nM for Akt1, Akt2 and Akt3, respectively. ^[1] AZD5363 inhibits phosphorylation of AKT substrates in cells with a potency of approximately 0.3 to 0.8 μM. AZD5363 inhibits the proliferation of 41 of 182 solid and hematologic tumor cell lines with a potency of < 3 μM. ^[2] Activating mutations in PIK3CA, loss or inactivation of tumor suppressor PTEN, or HER2 amplification all are significantly predictive of responsiveness to AZD5363. Additionally, correlation is also seen between the RAS mutation status of cell lines and resistance to AZD5363. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

PC-3	M2nJSGZ2dmO2aX;uJGF{e2G7	NHWzdI8yOCEQvF2=	MoPwNVIhcA>?	MmrxbY5lfWOnczDheZRweGijZ4m=	NYXK[odxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyOVg4PDBpPkKzNlU5PzRyPD;hQi=>
LNCaP	NYKzV3JxS2WubDDWbYFjcWyrdImgRZN{[Xl?	MlKwNE0yODByIH7N	MYiwMVQh\A>?	MmfEdoVlfWOnZDDMUmNiWCClZXzsJJZq[WKrbHn0fUBqdiCjIHTvd4UuKGGwZDD0bY1mNWSncHXu[IVvfCCvYX7u[ZLDqA>?	M1XSflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MkW4O\|QxLz5{M{K1PFc1ODxxYU6=
DU145	MX7GeY5kfGmxbjDBd5NigQ>?	NGi1OY0xNjVxMT:xNEDPxE1?	M2PEflQ5KGh?	NFn5XHBld3ewcnXneYxifGW\|IITo[UBxcG:\|cHjvdplt[XSrb36gc4Yh\G:5boP0doVidSCyYYToe4F6KHC{b4TlbY5{KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	NUnxfZdoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyOVg4PDBpPkKzNlU5PzRyPD;hQi=>
PC-3	NFj4[IZHfW6ldHnvckBCe3OjeR?=	MXiwMlUwOS9zMDFOwG0>	NWLmWppWPDhiaB?=	NXvJcmdk\G:5boLl[5Vt[XSnczD0bIUheGixc4Doc5J6dGG2aX;uJI9nKGSxd37zeJJm[W1icHH0bJdigSCycn;0[YlveyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	Mlu2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{NUi3OFAoRjJ\|MkW4O\|QxRC:jPh?=
C4-2	M2fDV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NEXDRZEyODBvNUCwNEBvVQ>?	MoL2O\|IhcA>?	Ml7YbY5kemWjc3XzJJRp\SCocnHjeIlwdiCxZjDj[YxteyC3bnTldodwcW6pIHPlcIwh\GWjdHi=	MoSwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7Nk[2NlEoRjJ\|OU[2OlIyRC:jPh?=
LNCaP	MoD4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NWjNWVVZOTByLUWwNFAhdk1?	NGC3N444OiCq	MoXBbY5kemWjc3XzJJRp\SCocnHjeIlwdiCxZjDj[YxteyC3bnTldodwcW6pIHPlcIwh\GWjdHi=	M4LPR\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OU[2OlIyLz5{M{m2OlYzOTxxYU6=
C4-2	M2Hvb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NWfqT\|FjOS1zMECwNEBvVQ>?	NYnpSodWOC1\|IHS=	NGTvcllqdmirYnn0d{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7	MmL2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7Nk[2NlEoRjJ\|OU[2OlIyRC:jPh?=
LNCaP	M3n1eWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NWDMSXByOS1zMECwNEBvVQ>?	NH3B[YcxNTNiZB?=	MX7pcohq[mm2czDj[YxtKH[rYXLpcIl1gSCmb4PlJIRmeGWwZHXueIx6	M4DNbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OU[2OlIyLz5{M{m2OlYzOTxxYU6=
C4-2	M2DOc2Z2dmO2aX;uJGF{e2G7	MmiwOUDPxE1?	M4Du[\|AuOjRiaB?=	MWLpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[geIhmKGSrc4ThcEBCU1RvcHH0bJdigSCkaX;tZZJs\XK\|IHnuZ4x2\GmwZzDQVmFUPDBuIHXJSlRGNCB2RT3CVFEtKG2WT2KsJIFv\CCSN{CgV\|Yhc2mwYYPlJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy	NHzP[m49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2OlYzOSd-MkO5OlY3OjF:L3G+
LNCaP	MYPGeY5kfGmxbjDBd5NigQ>?	MnLYOUDPxE1?	Mlz4NE0zPCCq	MYHpcohq[mm2czDwbI9{eGixconsZZRqd25ib3[geIhmKGSrc4ThcEBCU1RvcHH0bJdigSCkaX;tZZJs\XK\|IHnuZ4x2\GmwZzDQVmFUPDBuIHXJSlRGNCB2RT3CVFEtKG2WT2KsJIFv\CCSN{CgV\|Yhc2mwYYPlJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl4Nk[yNUc,OjN7Nk[2NlE9N2F-
C4-2	M1rtbGZ2dmO2aX;uJGF{e2G7	Mo\wOUDPxE1?	MlHENE0zPCCq	Ml6xbY5lfWOnczDBT3RUPDd\|IHHu[EBCU1SWM{C4JJBpd3OyaH;yfYxifGmxbjDpckBiKHSrbXWg[IVx\W6mZX70JI1idm6nch?=	NXz0cG5{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OlY3OjFpPkKzPVY3PjJzPD;hQi=>
LNCaP	NGLOS2dHfW6ldHnvckBCe3OjeR?=	M2TKVlUh\|ryP	M{PzSVAuOjRiaB?=	M{TrN4lv\HWlZYOgRWtVWzR5MzDhcoQhSUuWVEOwPEBxcG:\|cHjvdplt[XSrb36gbY4h[SC2aX3lJIRmeGWwZHXueEBu[W6wZYK=	NIPxSo09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2OlYzOSd-MkO5OlY3OjF:L3G+
PAMC82	NGrWPItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M{SwO2lEPTB;M{Cg{txO	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6OEO4Nkc,OjRyOEizPFI9N2F-
MKN74	M{fK[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MV7JR\|UxRTNyIN88US=>	NVPzemlTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPFg{QDJpPkK0NFg5Ozh{PD;hQi=>
GTL-16	MoSxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MoroTWM2OD1\|MDFOwG0>	NEfCXIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC4PFM5Oid-MkSwPFg{QDJ:L3G+
SNU-5	M1O3Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MV7JR\|UxRTNyIN88US=>	NUjZ[XZJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPFg{QDJpPkK0NFg5Ozh{PD;hQi=>
NUGC-4	M2H5W2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MkK2TWM2OD1\|MDFOwG0>	M2nrRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEi4N\|gzLz5{NEC4PFM5OjxxYU6=
SNU-216	MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NGTWRZdKSzVyPUOwJO69VQ>?	NYCwe3o4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPFg{QDJpPkK0NFg5Ozh{PD;hQi=>
AZ521	NITCbVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			Ml;nTWM2OD1{NT60OFgh\|ryP	MoSzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOEizPFIoRjJ2MEi4N\|gzRC:jPh?=
NUGC-3	M{fIbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MYHJR\|UxRTJzLki3N{DPxE1?	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6OEO4Nkc,OjRyOEizPFI9N2F-
OCUM-1	M1PCUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MYLJR\|UxRTF2LkWxOUDPxE1?	MlX4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOEizPFIoRjJ2MEi4N\|gzRC:jPh?=
SNU-16	M3rucmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NGfGWopKSzVyPUGxMlA6PyEQvF2=	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6OEO4Nkc,OjRyOEizPFI9N2F-
SNU-484	NYfGV4oyT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MmnBTWM2OD15LkO5NkDPxE1?	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6OEO4Nkc,OjRyOEizPFI9N2F-
KATO III	MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NXrKW3dRUUN3ME23MlI3PyEQvF2=	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6OEO4Nkc,OjRyOEizPFI9N2F-
HS746T	Ml\CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NVf1Z29KUUN3ME22MlA5PCEQvF2=	NXfRXndXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPFg{QDJpPkK0NFg5Ozh{PD;hQi=>
SNU-668	MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MnnnTWM2OD14LkCwN{DPxE1?	M4jxXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEi4N\|gzLz5{NEC4PFM5OjxxYU6=
SNU-601	M4H6WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NX;0dm57UUN3ME21Mlk{QCEQvF2=	M33PO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEi4N\|gzLz5{NEC4PFM5OjxxYU6=
SNU-1	M37JWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NHPNdZNKSzVyPUWuNlU5KM7:TR?=	NH3ncYs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC4PFM5Oid-MkSwPFg{QDJ:L3G+
SNU-638	NFm3elRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M{HJcmlEPTB;ND61NlMh\|ryP	Mm\kQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOEizPFIoRjJ2MEi4N\|gzRC:jPh?=
SNU-620	NWLmR2xxT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NGnlbHhKSzVyPUOuN\|g1KM7:TR?=	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6OEO4Nkc,OjRyOEizPFI9N2F-
MKN1	NEnuOnJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NXnadJZQUUN3ME2yMlQzOSEQvF2=	NUnSbY1{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPFg{QDJpPkK0NFg5Ozh{PD;hQi=>
23132/87	Mn;LS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M1nFSGlEPTB;MT62O\|Eh\|ryP	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6OEO4Nkc,OjRyOEizPFI9N2F-
NCI-N87	NEHiNI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MVfJR\|UxRTFwMEO3JO69VQ>?	MojPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOEizPFIoRjJ2MEi4N\|gzRC:jPh?=
AGS	MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NUnzXHNVUUN3ME2wMlU2OiEQvF2=	NHntS\|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC4PFM5Oid-MkSwPFg{QDJ:L3G+
IM95m	NXfpR\|R1T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M4\XW2lEPTB;MD61NUDPxE1?	Ml76QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOEizPFIoRjJ2MEi4N\|gzRC:jPh?=
HGC27	NGfOb3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M2fsbGlEPTB;MD60OFUh\|ryP	NXT1dGNrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPFg{QDJpPkK0NFg5Ozh{PD;hQi=>
PC-9	MVLGeY5kfGmxbjDBd5NigQ>?	M4Xxe\|EwPS9zMDFOwG0>	MVq0M\|I1KGh?	MmnrbY5kemWjc3XzJGFMXCCyaH;zdIhwenmuYYTpc44>	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl3N{[4Nkc,OjR7NUe2PFI9N2F-
NCI-H522	NXe5[HRSTnWwY4Tpc44hSXO\|YYm=	MUexM\|UwOTBizszN	M2H3elQwOjRiaB?=	MkK5bY5kemWjc3XzJGFMXCCyaH;zdIhwenmuYYTpc44>	NFH0W\|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEm1O\|Y5Oid-MkS5OVc3QDJ:L3G+
PC-9	NEf5dG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NHrrSohKSzVyPUmuN{ApyrFzLkKpJO69VQ>?	NULpXXNKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5OVc3QDJpPkK0PVU4Pjh{PD;hQi=>
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LAN-5	NGTpWJRyUFSVIHHzd4F6			MVvxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN?	NIDLRYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh18	NVrOV\|ZSeUiWUzDhd5NigQ>?			NWfzeItVeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoNVgh[2WubIO=	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	pAKT / AKT / pGSK3β / GSK3β ; HER3 / pHER3 / HER2 / pHER2 / pPRAS40 / pS6 / p-4EBP1 / pFOXO / pERK / PARP / Cleaved PARP	26998062 26095475
Immunofluorescence	p-Chk2 / γ-H2AX	29879757
Growth inhibition assay	Cell viability	29879757

In vivo

Oral dosing of AZD5363 (100, 300 mg/kg) to nude mice causes dose- and time-dependent reduction of PRAS40, GSK3β, and S6 phosphorylation in BT474c xenografts, reversible increases in blood glucose concentrations, and dose-dependent decreases in 2[¹⁸F]fluoro-2-deoxy-d-glucose (¹⁸F-FDG) uptake in U87-MG xenografts. Chronic oral dosing of AZD5363 (130, 200, and 300 mg/kg) causes dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2+ breast cancer models that are resistant to trastuzumab. AZD5363 also significantly enhances the antitumor activity of docetaxel, lapatinib, and trastuzumab in breast cancer xenografts. ^[2]

Protocol (from reference)

Kinase Assay:^[1]	Caliper Off-Chip Incubation Mobility Shift assay: The ability of AZD5363 and other compounds to inhibit the activity of AKT1, AKT2, and AKT3 is evaluated by the Caliper Off-Chip Incubation Mobility Shift assay. Active recombinant AKT1, AKT2, or AKT3 are incubated with a 5-FAM-labeled custom-synthesized peptide substrate together with increasing concentrations of inhibitor. Final reactions contained 1 to 3 nM AKT1, AKT2, or AKT3 enzymes; 1.5 mM peptide substrate; ATP at K _m for each AKT isoform; 10 mM MgCl₂, 4 mM DTT, 100 mM HEPES, and 0.015% Brij-35. The reactions are incubated at room temperature for 1 hour and stopped by the addition of buffer containing 100 mM HEPES, 0.015% Brij-35 solution, 0.1% coating reagent, 40 mM EDTA, and 5% DMSO. Plates are then analyzed using a Caliper LC3000, allowing for separation of peptide substrate and phosphorylated product by electrophoresis with subsequent detection and quantification of laser induced fluorescence.
Cell Research: ^[2]	Cell lines: 182 solid and hematologic tumor cell lines Concentrations: ~30 μM Incubation Time: 72 hours Method: Cell proliferation assay is determined by 2 methods, MTS and Sytox Green. Briefly, cells are seeded in 96-well plates and incubated overnight at 37 ℃, 5% CO₂. Cells are then exposed to concentrations of AZD5363 ranging from 30 to 0.003μM for 72 hours. For the MTS endpoint, cell proliferation is measured by the CellTiter AQueous Non-Radioactive Cell Proliferation Assay reagent in accordance with the manufacturer's protocol. For the Sytox Green endpoint, Sytox Green nucleic acid dye diluted in TBS-EDTA buffer is added to cells (final concentration of 0.13 μM) and the number of dead cells detected using an Acumen Explorer. Cells are then permeabilized by the addition of saponin (0.03% final concentration, diluted in TBS-EDTA buffer), incubated overnight and a total cell count measured. Predose measurements are made for both MTS and Sytox Green endpoints, and concentration needed to reduce the growth of treated cells to half that of untreated cells values are determined using absorbance readings (MTS) or live cell counts.
Animal Research:^[2]	Animal Models: Female nude mice and male SCID mice with BT474c, U87MG, KPL-4, HCC-1187 xenografts. Dosages: 130 mg/Kg - 300 mg/Kg Administration: p.o.

References

Solubility (25°C)

In vitro	DMSO	86 mg/mL (200.5 mM)
	Water	Insoluble
	Ethanol	Insoluble

Chemical Information

Molecular Weight	428.92
Formula	C₂₁H₂₅ClN₆O₂
CAS No.	1143532-39-1
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	C1CN(CCC1(C(=O)NC(CCO)C2=CC=C(C=C2)Cl)N)C3=NC=NC4=C3C=CN4

Download Capivasertib (AZD5363) SDF

In vivo Formulation Calculator (Clear solution)

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

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03310541	Active not recruiting	Drug: AZD5363\|Drug: Enzalutamide\|Drug: Fulvestrant	Breast Cancer\|Prostate Cancer\|Advanced Solid Tumors	Memorial Sloan Kettering Cancer Center	October 11 2017	Phase 1
NCT01992952	Active not recruiting	Drug: AZD5363\|Drug: Placebo\|Drug: Fulvestrant	Estrogen Receptor Positive Breast Cancer	Velindre NHS Trust\|AstraZeneca\|Cenduit LLC\|Covance\|Cardiff and Vale University Health Board	May 2014	Phase 1\|Phase 2
NCT02338622	Completed	Drug: olaparib\|Drug: AZD5363	Advanced Cancer	Royal Marsden NHS Foundation Trust\|Institute of Cancer Research United Kingdom\|AstraZeneca	March 31 2014	Phase 1
NCT02121639	Active not recruiting	Drug: Placebo\|Drug: AZD5363	Prostate Cancer	University Hospital Southampton NHS Foundation Trust\|AstraZeneca\|Cancer Research UK	January 29 2014	Phase 1\|Phase 2
NCT02077569	Completed	Drug: AZD5363	Invasive Breast Cancer	University of Nottingham\|AstraZeneca\|Cancer Research UK\|National Cancer Research Network	January 2014	Phase 2
NCT01692262	Completed	Drug: Intermittent dosing of AZD5363	Metastatic Castrate-Resistant Prostate Cancer (mCRPC)\|Efficacy\|Safety and Tolerability\|Pharmacokinetics\|Pharmacodynamics\|Tumour Response.	AstraZeneca	November 2012	Phase 1

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

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