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AZD5363 (Capivasertib) Akt inhibitor

Name: AZD5363 (Capivasertib)
Brand: Selleck Chemicals
SKU: S8019
Availability: InStock
Rating: 5 (153 reviews)

Cat.No.S8019

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.

Chemical Structure

Molecular Weight: 428.92

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Quality Control

Batch: Purity: 99.60%

99.60

Related Targets	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Other Akt Inhibitors	SC79 MK-2206 Dihydrochloride Ipatasertib (GDC-0068) Perifosine GSK690693 Triciribine (API-2) Afuresertib (GSK2110183) CCT128930 Akti-1/2 A-674563 HCl

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
PC-3	Function Assay	10 μM	12 h	induces autophagy	23258740
LNCaP	Cell Viability Assay	0-1000 nM	0-4 d	reduced LNCaP cell viability in a dose- and time-dependent manner	23258740
DU145	Function Assay	0.5/1/10 μM	48 h	downregulates the phosphorylation of downstream pathway proteins in a dose-dependent manner	23258740
PC-3	Function Assay	0.5/1/10 μM	48 h	downregulates the phosphorylation of downstream pathway proteins in a dose-dependent manner	23258740
C4-2	Growth Inhibition Assay	100-5000 nM	72 h	increases the fraction of cells undergoing cell death	23966621
LNCaP	Growth Inhibition Assay	100-5000 nM	72 h	increases the fraction of cells undergoing cell death	23966621
C4-2	Growth Inhibition Assay	1-10000 nM	0-3 d	inhibits cell viability dose dependently	23966621
LNCaP	Growth Inhibition Assay	1-10000 nM	0-3 d	inhibits cell viability dose dependently	23966621
C4-2	Function Assay	5 μM	0-24 h	inhibits phosphorylation of the distal AKT-pathway biomarkers including PRAS40, eIF4E, 4E-BP1, mTOR, and P70 S6 kinase in a time-dependent manner	23966621
LNCaP	Function Assay	5 μM	0-24 h	inhibits phosphorylation of the distal AKT-pathway biomarkers including PRAS40, eIF4E, 4E-BP1, mTOR, and P70 S6 kinase in a time-dependent manner	23966621
C4-2	Function Assay	5 μM	0-24 h	induces AKTS473 and AKTT308 phosphorylation in a time dependent manner	23966621
LNCaP	Function Assay	5 μM	0-24 h	induces AKTS473 and AKTT308 phosphorylation in a time dependent manner	23966621
PAMC82	Growth Inhibition Assay			IC50=30 μM	24088382
MKN74	Growth Inhibition Assay			IC50=30 μM	24088382
GTL-16	Growth Inhibition Assay			IC50=30 μM	24088382
SNU-5	Growth Inhibition Assay			IC50=30 μM	24088382
NUGC-4	Growth Inhibition Assay			IC50=30 μM	24088382
SNU-216	Growth Inhibition Assay			IC50=30 μM	24088382
AZ521	Growth Inhibition Assay			IC50=25.448 μM	24088382
NUGC-3	Growth Inhibition Assay			IC50=21.873 μM	24088382
OCUM-1	Growth Inhibition Assay			IC50=14.515 μM	24088382
SNU-16	Growth Inhibition Assay			IC50=11.097 μM	24088382
SNU-484	Growth Inhibition Assay			IC50=7.392 μM	24088382
KATO III	Growth Inhibition Assay			IC50=7.267 μM	24088382
HS746T	Growth Inhibition Assay			IC50=6.084 μM	24088382
SNU-668	Growth Inhibition Assay			IC50=6.003 μM	24088382
SNU-601	Growth Inhibition Assay			IC50=5.938 μM	24088382
SNU-1	Growth Inhibition Assay			IC50=5.258 μM	24088382
SNU-638	Growth Inhibition Assay			IC50=4.523 μM	24088382
SNU-620	Growth Inhibition Assay			IC50=3.384 μM	24088382
MKN1	Growth Inhibition Assay			IC50=2.421 μM	24088382
23132/87	Growth Inhibition Assay			IC50=1.671 μM	24088382
NCI-N87	Growth Inhibition Assay			IC50=1.037 μM	24088382
AGS	Growth Inhibition Assay			IC50=0.552 μM	24088382
IM95m	Growth Inhibition Assay			IC50=0.51 μM	24088382
HGC27	Growth Inhibition Assay			IC50=0.445 μM	24088382
PC-9	Function Assay	1/5/10 μM	4/24 h	increases AKT phosphorylation	24957682
NCI-H522	Function Assay	1/5/10 μM	4/24 h	increases AKT phosphorylation	24957682
PC-9	Growth Inhibition Assay			IC50=9.3 (±1.2) μM	24957682
NCI-H522	Growth Inhibition Assay			IC50=11.3 (±2.7) μM	24957682
MR49F	Growth Inhibition Assay	0-5 μM	48 h	inhibits cell growth in a dose dependent manner	25151012
MR49C	Growth Inhibition Assay	0-5 μM	48 h	inhibits cell growth in a dose dependent manner	25151012
SKBR3	Growth Inhibition Assay	0-1.35 μM	5 d	enhances the growth inhibition of AZD8931	26095475
KPL4	Growth Inhibition Assay	0-1.35 μM	5 d	enhances the growth inhibition of AZD8931	26095475
BT474c	Growth Inhibition Assay	0-1.35 μM	5 d	enhances the growth inhibition of AZD8931	26095475
HCC1954	Growth Inhibition Assay	0-1.35 μM	5 d	enhances the growth inhibition of AZD8931	26095475
TamR	Growth Inhibition Assay	400 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
T74D LTED	Growth Inhibition Assay	100 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
ZR75 LTED	Growth Inhibition Assay	100 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
MCF7 LTED	Growth Inhibition Assay	200 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
1%MCF7	Growth Inhibition Assay	400 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
T74D	Growth Inhibition Assay	100 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
ZR75	Growth Inhibition Assay	100 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
MCF7	Growth Inhibition Assay	200 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
LNCaP	Function assay			Inhibition of Akt in PTEN-deficient human LNCaP cells assessed as phosphorylation of GSK3beta, IC50 = 0.06 μM.	23394218
MDA-MB-468	Function assay		2 hrs	Inhibition of Akt in human MDA-MB-468 cells assessed as inhibition of GSK3beta phosphorylation after 2 hrs by laser scanning cytometry, IC50 = 0.089 μM.	23394218
LNCaP	Function assay			Inhibition of Akt in PTEN-deficient human LNCaP cells assessed as phosphorylation of PRAS40, IC50 = 0.22 μM.	23394218
BT474c	Function assay			Inhibition of Akt in human BT474c cells harboring HER2+/PIK3CA double mutant assessed as phosphorylation of PRAS40, IC50 = 0.31 μM.	23394218
MDA-MB-468	Function assay			Inhibition of Akt in PTEN-deficient human MDA-MB-468 cells assessed as phosphorylation of GSK3beta, IC50 = 0.38 μM.	23394218
MDA-MB-468	Function assay			Inhibition of Akt in PTEN-deficient human MDA-MB-468 cells assessed as phosphorylation of PRAS40, IC50 = 0.39 μM.	23394218
BT474c	Function assay			Inhibition of Akt in human BT474c cells harboring HER2+/PIK3CA double mutant assessed as phosphorylation of GSK3beta, IC50 = 0.76 μM.	23394218
RT4	Function assay			Inhibition of PKA in TSC1 deficient human RT4 cells assessed as S6 phosphorylation, IC50 = 1 μM.	23394218
RT4	Function assay			Inhibition of P70S6K in TSC1 deficient human RT4 cells assessed as S6 phosphorylation, IC50 = 5 μM.	23394218
PTEN-null LNCAP	Function assay		1 hr	Inhibition of Akt in human PTEN-null LNCAP cells assessed as suppression in PRAS40 phosphorylation after 1 hr by ELISA analysis, IC50 = 0.3368 μM.	27089211
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50 = 5.2 μM.	27089211
OVCAR8	Antiproliferative assay		72 hrs	Antiproliferative activity against human OVCAR8 cells after 72 hrs by SRB assay, IC50 = 7.27 μM.	27089211
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 86 mg/mL (200.5 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 20 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.300mg/ml (10.03mM)	Taking the 1 mL working solution as an example, add 50 μL 86 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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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. )

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Chemical Information, Storage & Stability

Molecular Weight	428.92	Formula	C₂₁H₂₅ClN₆O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1143532-39-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1CN(CCC1(C(=O)NC(CCO)C2=CC=C(C=C2)Cl)N)C3=NC=NC4=C3C=CN4

Mechanism of Action

Features	Moderate preclinical tolerability, and PD characteristics of an AKT inhibitor. Distinct profile from other AKT inhibitors in clinical development.
Targets/IC₅₀/Ki	Akt1 (Cell-free assay) 3 nM Akt2 (Cell-free assay) 8 nM Akt3 (Cell-free assay) 8 nM ROCK2 (Cell-free assay) 56 nM
In vitro	Capivasertib (AZD5363) is a potent Akt inhibitor with IC50 of 3 nM, 8 nM and 8 nM for Akt1, Akt2 and Akt3, respectively. It inhibits phosphorylation of AKT substrates in cells with a potency of approximately 0.3 to 0.8 μM. This compound inhibits the proliferation of 41 of 182 solid and hematologic tumor cell lines with a potency of < 3 μM. 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 it.
Kinase Assay	Caliper Off-Chip Incubation Mobility Shift assay
Kinase Assay	The ability of Capivasertib (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 this compound. 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.
In vivo	Oral dosing of Capivasertib (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 this compound (130, 200, and 300 mg/kg) causes dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2+ breast cancer models.
References	[1] http://www.ncbi.nlm.nih.gov/pubmed/?term=23394218 [2] http://www.ncbi.nlm.nih.gov/pubmed/?term=22294718

Applications

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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03310541	Completed	Breast Cancer\|Prostate Cancer\|Advanced Solid Tumors	Memorial Sloan Kettering Cancer Center	October 11 2017	Phase 1
NCT01992952	Active not recruiting	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	Advanced Cancer	Royal Marsden NHS Foundation Trust\|Institute of Cancer Research United Kingdom\|AstraZeneca	March 31 2014	Phase 1
NCT02121639	Completed	Prostate Cancer	University Hospital Southampton NHS Foundation Trust\|AstraZeneca\|Cancer Research UK	January 29 2014	Phase 1\|Phase 2
NCT02077569	Completed	Invasive Breast Cancer	University of Nottingham\|AstraZeneca\|Cancer Research UK\|National Cancer Research Network	January 2014	Phase 2
NCT01692262	Completed	Metastatic Castrate-Resistant Prostate Cancer (mCRPC)\|Efficacy\|Safety and Tolerability\|Pharmacokinetics\|Pharmacodynamics\|Tumour Response.	AstraZeneca	November 2012	Phase 1

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