General
Preferred name
IPATASERTIB
Synonyms
Ipatasertib dihydrochloride ()
RG-7440 dihydrochloride ()
GDC 0068 ()
GDC-0068 ()
GDC0068 ()
RG 7440 ()
RG-7440 ()
RG7440 ()
GDC-0068 (dihydrochloride) ()
RG-7440 (dihydrochloride) ()
Ipatasertib (dihydrochloride) ()
GDC-0068 dihydrochloride ()
Ipatasertib (GDC-0068) ()
P&D ID
PD017093
CAS
1001264-89-6
1396257-94-5
Tags
available
drug candidate
Drug indication
Gastric adenocarcinoma
Breast cancer
Solid tumour/cancer
Prostate cancer
Colorectal cancer
Drug Status
investigational
Max Phase
3.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
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 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)
Cell lines
14
Organisms
0
Compound Sets
20
AdooQ Bioactive Compound Library
A11246
BOC Sciences Bioactive Compounds
gdc-0068-dihydrochloride-cas-1396257-94-5-item-84-463214
Cayman Chemical Bioactives
18412
ChEMBL Drugs
CHEMBL2177390
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB11743
DrugMAP
DMWBZJD
EU-OPENSCREEN Bioactive Compound Library
EOS101508
Guide to Pharmacology
7887
LINCS compound set
10338-101
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL2177390
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
CHEMBL2177390
Mcule NIBR MoA Box Subset
MCULE-8925317592
MedChem Express Bioactive Compound Library
HY-15186A
HY-15186
Novartis Chemogenetic Library (NIBR MoA Box)
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
gdc-0068
TargetMol Bioactive Compound Library
T6252
External IDs
38
Properties
(calculated by RDKit )
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)
Pathway
Cytoskeletal Signaling
PI3K/Akt/mTOR signaling
Apoptosis
PI3K/Akt/mTOR
Stem Cell/Wnt
Target
AKT1
AKT2
AKT3
AKT1, AKT2, AKT3, PRKG1
Akt
Organoid
Member status
member
MOA
Akt inhibitor
Source data