General
Preferred name
IPATASERTIB
Synonyms
GDC 0068 ()
GDC-0068 ()
GDC0068 ()
RG 7440 ()
RG-7440 ()
RG7440 ()
GDC-0068 dihydrochloride ()
RG-7440 dihydrochloride ()
Ipatasertib (dihydrochloride) ()
GDC-0068 (dihydrochloride) ()
RG-7440 (dihydrochloride) ()
Ipatasertib (GDC-0068) ()
Ipatasertib dihydrochloride ()
P&D ID
PD017093
CAS
1001264-89-6
1396257-94-5
Tags
available
drug candidate
Drug indication
Breast cancer
Prostate cancer
Gastric adenocarcinoma
Solid tumour/cancer
metastatic prostate cancer
Colorectal cancer
Drug Status
investigational
Max Phase
3.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
Ipatasertib dihydrochloride (GDC-0068 dihydrochloride) is a highly selective and ATP-competitive pan-Akt inhibitor with IC50s of 5, 18 and 8 nM for Akt1, Akt2 and Akt3, respectively.
DESCRIPTION
Ipatasertib is an inhibitor of the AKT family of protein kinases . The synthesis of ipatasertib is described in patent WO2008006040 and where it is compound 28 (the Supporting Information for this article contains activity data for compound 28 against a full kinase screening panel). This compound is also represented on PubChem by CID 23649210.
(GtoPdb)
DESCRIPTION
Ipatasertib (GDC-0068) is an orally active, highly selective and ATP-competitive pan-Akt inhibitor with IC50 values of 5, 18, 8 nM for Akt1/2/3, respectively. Ipatasertib synchronously activates FoxO3a and NF-¦ÊB through inhibition of Akt leading to p53-independent activation of PUMA. Ipatasertib also induces apoptosis in cancer cells and inhibits tumor growth in xenograft mouse models[1][2].
PRICE
75
DESCRIPTION
Ipatasertib (GDC-0068) is a selective, ATP-competitive pan-Akt inhibitor that inhibits Akt1 (IC50:5 nM), Akt2 (IC50:18 nM), and Akt3 (IC50:8 nM). Ipatasertib (GDC-0068) can lead to p53-independent PUMA activation by inhibiting Akt, thereby activating FoxO3a and NF-??B simultaneously, directly binding to the PUMA promoter, upregulating PUMA transcription and Bax-mediated intrinsic mitochondrial apoptosis.
DESCRIPTION
Testing against a broad panel of 230 kinases, GDC-0068 only inhibits 3 kinases by >70% at 1 μM concentration (PRKG1α, PRKG1β, and p70S6K, with IC50 of 98 nM, 69 nM, and 860 nM, respectively). GDC-0068 displays >100-fold selectivity for Akt over PKA with IC50 of 3.1 μM. In LNCaP, PC3 and BT474M1 cells, GDC-0068 treatment inhibits the phosphorylation of the Akt substrate, PRAS40 with IC50 of 157 nM, 197 nM, and 208 nM, respectively. Furthermore, GDC-0068 selectively inhibits cell cycle progression and viability of cancer cell lines driven by Akt signaling, including those with defects in the tumor suppressor PTEN, oncogenic mutations in PIK3CA, and amplification of HER2, with strongest effects in HER2+ and Luminal subtypes.
Oral administration of GDC-0068 in PC3 prostate tumor xenografts model induces down-regulation of p-PRAS40. In BT474-Tr xenografts, GDC-0068 treatment reduces pS6 and peIF4G levels, re-localizes FOXO3a to nucleus, and induces feedback upregulation of HER3 and pERK. Administration of GDC-0068 exhibits potent antitumor efficacy in multiple xenograft tumor models, including the PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and MCF7-neo/HER2 tumor model. (BOC Sciences Bioactive Compounds)
Oral administration of GDC-0068 in PC3 prostate tumor xenografts model induces down-regulation of p-PRAS40. In BT474-Tr xenografts, GDC-0068 treatment reduces pS6 and peIF4G levels, re-localizes FOXO3a to nucleus, and induces feedback upregulation of HER3 and pERK. Administration of GDC-0068 exhibits potent antitumor efficacy in multiple xenograft tumor models, including the PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and MCF7-neo/HER2 tumor model. (BOC Sciences Bioactive Compounds)
DESCRIPTION
Ipatasertib dihydrochloride (GDC-0068 dihydrochloride) is a highly selective, ATP-competitive inhibitor of pan-Akt, with IC50 values of 5 nM, 18 nM, and 8 nM for Akt1, Akt2, and Akt3, respectively.
(TargetMol Bioactive Compound Library)
DESCRIPTION
Ipatasertib (GDC-0068) is a selective, ATP-competitive pan-Akt inhibitor that inhibits Akt1 (IC50:5 nM), Akt2 (IC50:18 nM), and Akt3 (IC50:8 nM). Ipatasertib (GDC-0068) can lead to p53-independent PUMA activation by inhibiting Akt, thereby activating FoxO3a and NF-κB simultaneously, directly binding to the PUMA promoter, upregulating PUMA transcription and Bax-mediated intrinsic mitochondrial apoptosis.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
16
Organisms
0
Compound Sets
20
AdooQ Bioactive Compound Library
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Drugs
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugMAP
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
LINCS compound set
LSP-MoA library (Laboratory of Systems Pharmacology)
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
Novartis Chemogenetic Library (NIBR MoA Box)
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
38
Molecular Weight
457.22
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
6
Ring Count
4
Aromatic Ring Count
2
cLogP
3.1
TPSA
81.59
Fraction CSP3
0.54
Chiral centers
3.0
Largest ring
6.0
QED
0.69
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
AKT1
AKT2
AKT3
PKA
Akt
AKT1, AKT2, AKT3, PRKG1
Apoptosis
Organoid
Member status
member
MOA
Akt inhibitor
Pathway
Cytoskeletal Signaling
PI3K/Akt/mTOR signaling
Tyrosine Kinase/Adaptors
PI3K/Akt/mTOR
Stem Cell/Wnt
Source data
