General
Preferred name
PICTILISIB
Synonyms
GDC-0941 ()
GDC0941 ()
RG-7321, GDC-0941 ()
GDC-0941 dimethanesulfonate ()
GDC-0941 2 MeSO3H salt ()
RG7321 ()
Pictrelisib ()
RG-7321 ()
Pictilisib dimethanesulfonate ()
GDC 0941 bismesylate ()
GDC-0941 (dimethanesulfonate) ()
GDC-0941 (2 MeSO3H salt) ()
Pictilisib (dimethanesulfonate) ()
CDC-0941 ()
GDC 0941 ()
Pictilisib (GDC-0941) ()
P&D ID
PD003253
CAS
957054-30-7
957054-33-0
Tags
available
probe
drug candidate
Drug indication
Non-hodgkin lymphoma
Breast cancer
Solid tumour/cancer
Drug Status
investigational
Max Phase
2.0
Probe info
Probe type
calculated probe
experimental probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
71
No orthogonal probes found
Similar probes
8
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
Pictilisib is a potent and orally bioavailable inhibitor of Class I phosphatidylinositol-3 kinase family proteins .
(GtoPdb)
COMMENT
GDC-0941 is an inhibitor of class I PI3 kinases (IC50 α, β, δ, γ = 3, 33, 3, 75 nM, respectively) with selectivity over class II, III and IV enzymes C2β (670 nM), Vps34 (>10 µM), DNA-PK (1.23 µM) and mTOR (580 nM). Greater than 300-fold selectivity for the α-isoform versus an additional 228 kinases was also described. Cellular activity against tumor cell lines was reported as EC50 = 140-950 nM while inhibition of cellular target engagement (pAkt473) occurred at lower exposures (EC50 = 28-46 nM). In vivo target engagement and tumor growth inhibition were reported following oral administration to mice (25-150 mg/kg/d). This tool is recommended for use in preference to the older, less selective inhibitors such as wortmannin and LY294002. Jun 12 2016 - 4:09am; Chemical Neighbourhood for QSAR: 129, 47, and 24 molecules similar (>0.80) to GDC-0941 with in vitro affinities for PIK3CA, PIK3CD, and PIK3CB, respectively, were found in public repositories (e.g., ChEMBL). Jul 13 2016 - 4:29pm; For cell culture, I would recommend confirming class I inhibition without inhibition of the other classes (class II-class IV). However, because cell-free sensitivities of the p110s vary from 3 nM (alpha) to 75 nM (gamma, 25-fold of alpha) and cellular sensitivities of classes II and IV are relatively higher, a careful dose-response study in cells should be conducted before conclusions are drawn from the data. Jul 14 2016 - 11:07pm
MOA
ATP-competitive inhibitor
(Chemical Probes.org)
DESCRIPTION
inhibitor of PI3K kinase activity
(Informer Set)
DESCRIPTION
GDC-0941 dimethanesulfonate is a potent inhibitor of PI3Kα/δ with modest selectivity against p110β and p110γ. It is a novel selective class I phosphatidylinositol-3-kinase (PI3K) inhibitor. It is designed to bind the ATP-binding pocket of PI3K and to prevent formation of phosphatidylinositol-3, 4, 5-triphosphate (PIP3), a second messenger that transmits PI3K downstream signals. It causes growth inhibition in a variety of cancer cell lines, including A2780, MDA-MB-361, PC3, and U87MG. It also inhibits the growth of trastuzumab-sensitive and -resistant HER2-amplied cancer cells which harbor p110( mutations or PTEN loss. It also reduces tumor volume in different xenograft models.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
502
Organisms
1
Compound Sets
33
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Drugs
Chemical Probes.org
Clinical kinase drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugMAP
EU-OPENSCREEN Bioactive Compound Library
EUbOPEN Chemogenomics Library
Guide to Pharmacology
High-quality chemical probes
Informer Set
Kinase Inhibitors (best-in-class)
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
Tool Compound Set
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
44
Molecular Weight
513.16
Hydrogen Bond Acceptors
9
Hydrogen Bond Donors
1
Rotatable Bonds
5
Ring Count
6
Aromatic Ring Count
4
cLogP
2.15
TPSA
107.55
Fraction CSP3
0.43
Chiral centers
0.0
Largest ring
6.0
QED
0.43
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
PIK3CA
PIK3CB
PIK3CD
PIK3CG
PI3K (class 1)
PI3K
PI3-kinase p110-alpha subunit
PI3-kinase p110-delta subunit
DNA-PK
MTOR
p110??
p110??-E545K
p110??-H1047R
PIK3CA, PIK3CB, PIK3CD, PIK3CG
Apoptosis related,Autophagy,PI3K
PIK3CA, PIK3CD
Compound status
clinical
Pathway
PI3K signaling
Autophagy
DNA Damage/DNA Repair
PI3K/Akt/mTOR signaling
Apoptosis
PI3K/Akt/mTOR
Kinase group
Lipid
Targets
PIK3CA,PIK3CD
Member status
member
MOA
panPI3K inhibitor
PI3K inhibitor
Target subclass
Class I
Class I, Class I
Target class
Lipid kinase
Lipid kinase, Lipid kinase
Orthogonal probe
BYL-719
Recommended Cell Concentration
1 µM
Source data
