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Details

Stereochemistry ACHIRAL
Molecular Formula C23H27N7O3S2
Molecular Weight 513.636
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PICTILISIB

SMILES

CS(=O)(=O)N1CCN(CC2=CC3=C(S2)C(=NC(=N3)C4=CC=CC5=C4C=NN5)N6CCOCC6)CC1

InChI

InChIKey=LHNIIDJUOCFXAP-UHFFFAOYSA-N
InChI=1S/C23H27N7O3S2/c1-35(31,32)30-7-5-28(6-8-30)15-16-13-20-21(34-16)23(29-9-11-33-12-10-29)26-22(25-20)17-3-2-4-19-18(17)14-24-27-19/h2-4,13-14H,5-12,15H2,1H3,(H,24,27)

HIDE SMILES / InChI

Molecular Formula C23H27N7O3S2
Molecular Weight 513.636
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Pictilisib is an oral potent inhibitor of class I PI3K with nanomolar activities against p110alpha, p110beta, p110delta, and p110gamma. The drug was developed for the treatment of solid tumors and reached phase II in patients with breast cancer and lung carcinoma, however its development was terminated.

CNS Activity

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.0 nM [IC50]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer .
2008 Sep 25
High-throughput screening compatible cell-based assay for interrogating activated notch signaling.
2009 Feb
Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941.
2009 Jul
Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab.
2009 Jun 15
Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941.
2009 May 5
Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39.
2010 Apr
Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors.
2010 Feb 1
PIKing the right patient.
2010 Jul 15
Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models.
2010 Jul 15
Drugging the PI3 kinome: from chemical tools to drugs in the clinic.
2010 Mar 15
Physical association of PDK1 with AKT1 is sufficient for pathway activation independent of membrane localization and phosphatidylinositol 3 kinase.
2010 Mar 26
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Effects of nominally selective inhibitors of the kinases PI3K, SGK1 and PKB on the insulin-dependent control of epithelial Na+ absorption.
2010 Oct
Pharmacokinetic-pharmacodynamic modeling of tumor growth inhibition and biomarker modulation by the novel phosphatidylinositol 3-kinase inhibitor GDC-0941.
2010 Sep
Role of P-glycoprotein and breast cancer resistance protein-1 in the brain penetration and brain pharmacodynamic activity of the novel phosphatidylinositol 3-kinase inhibitor GDC-0941.
2010 Sep
Nuclear phospho-Akt increase predicts synergy of PI3K inhibition and doxorubicin in breast and ovarian cancer.
2010 Sep 8
Targeting a common collaborator in cancer development.
2010 Sep 8
Essential role of Stat3 in PI3K-induced oncogenic transformation.
2011 Aug 9
GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1α (HIF-1α) pathways.
2011 Dec
Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition.
2011 Jan 28
Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice.
2011 Mar 29
GDC-0941 sensitizes breast cancer to ABT-737 in vitro and in vivo through promoting the degradation of Mcl-1.
2011 Oct 1
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells.
2012
Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection.
2012
The antitumor effect of GDC-0941 alone and in combination with rapamycin in breast cancer cells.
2012
The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition.
2012 Apr 10
Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels.
2012 Aug
Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations.
2012 Aug
Diacylglycerol kinase δ1 transiently translocates to the plasma membrane in response to high glucose.
2012 Dec
Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models.
2012 Dec 15
Quantitative MRI establishes the efficacy of PI3K inhibitor (GDC-0941) multi-treatments in PTEN-deficient mice lymphoma.
2012 Feb
The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells.
2012 Feb
Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition.
2012 Jan 1
Genetic disruption of the PI3K regulatory subunits, p85α, p55α, and p50α, normalizes mutant PTPN11-induced hypersensitivity to GM-CSF.
2012 Jul
GDC-0941, a novel class I selective PI3K inhibitor, enhances the efficacy of docetaxel in human breast cancer models by increasing cell death in vitro and in vivo.
2012 Jul 15
Functional characterization of an isoform-selective inhibitor of PI3K-p110β as a potential anticancer agent.
2012 May
Gab2 regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells.
2012 May 17
Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice.
2012 Oct
Regulation of CD38 expression in human airway smooth muscle cells: role of class I phosphatidylinositol 3 kinases.
2012 Oct
Single cell network profiling assay in bladder cancer.
2013 Apr
A potent combination of the novel PI3K Inhibitor, GDC-0941, with imatinib in gastrointestinal stromal tumor xenografts: long-lasting responses after treatment withdrawal.
2013 Feb 1
Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment.
2013 Feb 1
GDC-0941 enhances the lysosomal compartment via TFEB and primes glioblastoma cells to lysosomal membrane permeabilization and cell death.
2013 Feb 1
Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas.
2013 Jan
Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations.
2013 Jan 17
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
2013 Nov
The PI3K inhibitor GDC-0941 combines with existing clinical regimens for superior activity in multiple myeloma.
2014 Jan 16
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.
2015 Jun
Patents

Sample Use Guides

In Vivo Use Guide
Patients with breast cancer receive paclitaxel (90 mg/m2 weekly for 3 weeks in every 28-day cycle) with 260 mg pictilisib (daily on days 1-5 every week).
Route of Administration: Oral
In Vitro Use Guide
Human breast tumor cell lines were treated with GDC-0941 (dose range 0.083–5 mM) to test cell viability in vitro.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:08:13 UTC 2019
Edited
by admin
on Mon Oct 21 23:08:13 UTC 2019
Record UNII
ICY00EMP8P
Record Status Validated (UNII)
Record Version
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Name Type Language
PICTILISIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
PICTILISIB [WHO-DD]
Common Name English
4-(2-(1H-INDAZOL-4-YL)-6-((4-(METHYLSULFONYL)PIPERAZIN-1-YL)METHYL)THIENO(3,2-D)PYRIMIDIN-4-YL)MORPHOLINE
Systematic Name English
PICTRELISIB
Common Name English
THIENO(3,2-D)PYRIMIDINE, 2-(1H-INDAZOL-4-YL)-6-((4-(METHYLSULFONYL)-1-PIPERAZINYL)METHYL)-4-(4-MORPHOLINYL)-
Systematic Name English
PICTILISIB [INN]
Common Name English
2-(1H-INDAZOL-4-YL)-6-((4-(METHANESULFONYL)PIPERAZIN-1-YL)METHYL)-4-(MORPHOLIN-4-YL)THIENO(3,2-D)PYRIMIDINE
Systematic Name English
PICTILISIB [MI]
Common Name English
CDC-0941
Code English
GDC 0941
Code English
GDC-0941
Code English
PICTILISIB [USAN]
Common Name English
Code System Code Type Description
EPA CompTox
957054-30-7
Created by admin on Mon Oct 21 23:08:13 UTC 2019 , Edited by admin on Mon Oct 21 23:08:13 UTC 2019
PRIMARY
INN
9417
Created by admin on Mon Oct 21 23:08:13 UTC 2019 , Edited by admin on Mon Oct 21 23:08:13 UTC 2019
PRIMARY
ChEMBL
CHEMBL521851
Created by admin on Mon Oct 21 23:08:13 UTC 2019 , Edited by admin on Mon Oct 21 23:08:13 UTC 2019
PRIMARY
EVMPD
SUB120770
Created by admin on Mon Oct 21 23:08:13 UTC 2019 , Edited by admin on Mon Oct 21 23:08:13 UTC 2019
PRIMARY
MERCK INDEX
M11673
Created by admin on Mon Oct 21 23:08:13 UTC 2019 , Edited by admin on Mon Oct 21 23:08:13 UTC 2019
PRIMARY
CAS
957054-30-7
Created by admin on Mon Oct 21 23:08:13 UTC 2019 , Edited by admin on Mon Oct 21 23:08:13 UTC 2019
PRIMARY
PUBCHEM
17755052
Created by admin on Mon Oct 21 23:08:13 UTC 2019 , Edited by admin on Mon Oct 21 23:08:13 UTC 2019
PRIMARY
Related Record Type Details
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