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Chemical Structure| 957054-30-7 Chemical Structure| 957054-30-7

Structure of Pictilisib
CAS No.: 957054-30-7

Chemical Structure| 957054-30-7

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Pictilisib (GDC-0941) is a potent PI3Kα/δ inhibitor with an IC50 of 3 nM, showing modest selectivity against p110β (11-fold) and p110γ (25-fold).

Synonyms: GDC-0941; GNE-0941; Pictrelisib

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Product Details of Pictilisib

CAS No. :957054-30-7
Formula : C23H27N7O3S2
M.W : 513.64
SMILES Code : CS(=O)(=O)N1CCN(CC2=CC3=C(S2)C(=NC(=N3)C2=C3C=NNC3=CC=C2)N2CCOCC2)CC1
Synonyms :
GDC-0941; GNE-0941; Pictrelisib
MDL No. :MFCD11616196
InChI Key :LHNIIDJUOCFXAP-UHFFFAOYSA-N
Pubchem ID :17755052

Safety of Pictilisib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Related Pathways of Pictilisib

PI3K-AKT

Isoform Comparison

Biological Activity

Target
  • p110γ

    p110γ, IC50:75 nM

  • p110β

    p110β, IC50:33 nM

  • p110α

    p110α, IC50:3 nM

  • p110δ

    p110δ, IC50:3 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MEB-Med-8A cells 1 μM 24 h Pictilisib significantly inhibited the migration of MEB-Med-8A cells and altered the cytoskeleton structure. PMC9716228
Daoy cells 1 μM 24 h Pictilisib reduced the migration of Daoy cells, significantly decreased wound closure, and altered the cytoskeleton structure. PMC9716228
KPwmC cells 1μM 30 min To observe the effect of Pictilisib on p-CREB1S133 levels, results showed that Pictilisib reduced p-CREB1S133 levels. PMC8338884
P14 CD8+ T cells 1 μM 3 to 4 days Inhibition of PI3K activity, leading to defective CD3 polarity and Glut1 surface trafficking, reduced glucose uptake PMC5806629
SW48-HER2 0.05 to 10 μM 96 h To evaluate the anti-proliferative effects of Pictilisib on SW48-HER2 cells. Results showed that Pictilisib as a single agent exhibited dose-dependent cell growth inhibition in HER2-amplified cells. PMC6549349
LIM1215-HER2 0.05 to 10 μM 96 h To evaluate the anti-proliferative effects of Pictilisib on LIM1215-HER2 cells. Results showed that Pictilisib as a single agent exhibited dose-dependent cell growth inhibition in HER2-amplified cells. PMC6549349
SW48-HER2 cells 0.05 to 10 μM 96 h To evaluate the inhibitory effect of Pictilisib on cell proliferation, the results showed that Pictilisib monotherapy exhibited dose-dependent growth inhibition in HER2-amplified cells. PMC6549349
LIM1215-HER2 cells 0.05 to 10 μM 96 h To evaluate the inhibitory effect of Pictilisib on cell proliferation, the results showed that Pictilisib monotherapy exhibited dose-dependent growth inhibition in HER2-amplified cells. PMC6549349
MIMCD3 cells 1 µM 10 h Pictilisib significantly reduced phosphorylation of Akt, MAPKAP1, and GFAP, and increased the formation of Dendra2 CMA reporter puncta, indicating an increase in CMA activity. PMC7557678
AML12 cells 2 µM 10 h Pictilisib significantly reduced phosphorylation of Akt, MAPKAP1, and GFAP, and increased the formation of Dendra2 CMA reporter puncta, indicating an increase in CMA activity. PMC7557678
NIH3T3 cells 500 nM 10 h Pictilisib significantly reduced phosphorylation of Akt, MAPKAP1, and GFAP, and increased the accumulation of Dendra2 CMA reporter puncta, indicating an increase in CMA activity. PMC7557678
Human NK cells 1 μM 2 hours To evaluate the effect of MLN1117 on human NK cell-mediated cytotoxicity. Results showed that selective inhibition of p110α had minimal impact on human NK cell-mediated cytotoxicity. PMC4051752

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice LIM1215-HER2 and SW48-HER2 tumor xenograft models Oral 75 mg/kg Once daily for 4 weeks To evaluate the antitumor activity of Pictilisib in LIM1215-HER2 and SW48-HER2 tumor xenograft models. Results showed that Pictilisib as a single agent had little effect on tumor growth, but the combination with Refametinib almost completely suppressed tumor growth. PMC6549349
Nude mice LIM1215-HER2 and SW48-HER2 tumor xenografts Oral 75 mg/kg Every day, for 4 weeks To evaluate the inhibitory effect of Pictilisib monotherapy and its combination with Refametinib on tumor growth, the results showed that the combination therapy significantly suppressed tumor growth and lasted up to 20 weeks after the end of treatment. PMC6549349
Mice Normal 3-month-old mice Oral 100 mg/kg Once per day for 7 days Pictilisib significantly increased CMA substrate uptake in liver lysosomes and reduced lysosomal GFAP phosphorylation in mice, indicating an increase in CMA activity. PMC7557678
Mice MR86 patient-derived xenograft (PDX) model Oral 150 mg/kg Once daily for up to 40 days To evaluate the inhibitory effect of Pictilisib in combination with Erdafitinib on tumor growth, the results showed that the combination treatment significantly inhibited tumor growth PMC10481128

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02430363 Glioblastoma Phase 1 Phase 2 Unknown June 2018 United States, Massachusetts ... More >> Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, Texas M D Anderson Cancer Center Houston, Texas, United States, 77030 Belgium UCL- Cliniques Universitaires Saint Luc Brussels, Belgium Germany St Johannes Hospital Duisburg, Germany, 47166 Italy Spedali Civili di Brescia Brescia, Italy IRCCS San Raffaele Milan, Italy Poland Lower-Silesian Oncology Centre Wroclaw, Lower-Silesian, Poland, 53413 Russian Federation Pavlov State Medical University St. Petersburg, Russian Federation, 197089 Spain Hospital Universitario Germans Trias I Pujol Barcelona,, Spain Switzerland Universitätsklinik für Frauenheilkunde Bern, Switzerland Ukraine Regional Cancer Center Dnepropetrovsk, Ukraine, 49000 National Institute of Cancer Kiev, Ukraine, 03035 United Kingdom Royal Victoria Hospital Belfast, Ulster, United Kingdom, BT12 6BA Less <<
NCT02389842 Advanced Solid Tumours ... More >> Breast Cancer Less << Phase 1 Unknown August 2017 United Kingdom ... More >> The Royal Marsden NHS Foundation Trust Recruiting London, United Kingdom, SM2 5PT Contact: Timothy Yap, PhD    02086613539    timothy.yap@icr.ac.uk    Principal Investigator: Timothy Yap, PhD          The Christie NHS Foundation Trust Not yet recruiting Manchester, United Kingdom, M20 4BX Contact: Anne Amstrong, MBBS    0161 446 3746    elaine.mercer@christie.nhs.uk    Principal Investigator: Anne Armstrong, MBBS Less <<
NCT02092831 Healthy Volunteer Phase 1 Completed - United States, Wisconsin ... More >> Madison, Wisconsin, United States, 53704 Less <<
NCT00960960 Breast Cancer Phase 1 Completed - United States, Illinois ... More >> Peoria, Illinois, United States, 61615 United States, Massachusetts Boston, Massachusetts, United States, 02115 United States, Tennessee Nashville, Tennessee, United States, 37232 Belgium Leuven, Belgium, 3000 Italy Milano, Lombardia, Italy, 20133 Less <<
NCT00974584 Non-Squamous Non-Small Cell Lu... More >>ng Cancer Less << Phase 1 Completed - United States, New York ... More >> Buffalo, New York, United States, 14263 France Villejuif, France, 94805 Netherlands Groningen, Netherlands, 9700 RB Less <<
NCT01493843 Non-Small Cell Lung Cancer Phase 2 Completed - -
NCT00999128 Healthy Volunteers Phase 1 Completed - United States, California ... More >> Genentech Trial Information Support South San Francisco, California, United States, 94080 Less <<
NCT01437566 Breast Cancer Phase 2 Completed - -
NCT00996892 Solid Tumors Phase 1 Terminated(A recommended Phase... More >> 2 dose and schedule was not identified and the study was terminated before initiation of Stage 2B.) Less << - United States, Maryland ... More >> Baltimore, Maryland, United States, 21231 United States, Massachusetts Boston, Massachusetts, United States, 02114 Boston, Massachusetts, United States, 02215 United States, Michigan Detroit, Michigan, United States, 48201 United States, Oklahoma Oklahoma City, Oklahoma, United States, 73104 United States, Tennessee Nashville, Tennessee, United States, 37203 Less <<
NCT00928330 Metastatic Breast Cancer Phase 1 Completed - United States, Indiana ... More >> Indianapolis, Indiana, United States, 46202 United States, Maryland Baltimore, Maryland, United States, 21231 United States, Massachusetts Boston, Massachusetts, United States, 02115 Less <<
NCT01240226 Healthy Volunteer Phase 1 Completed - United States, Texas ... More >> Investigational Site Austin, Texas, United States, 78744 Less <<
NCT00975182 Non-Squamous Non-Small Cell Lu... More >>ng Cancer, Solid Cancers Less << Phase 1 Completed - United States, Colorado ... More >> Aurora, Colorado, United States, 80045 United States, New Jersey New Brunswick, New Jersey, United States, 08903 Netherlands Amsterdam, Netherlands, 1066 EC Utrecht, Netherlands, 3508 GA Less <<
NCT01474668 Healthy Volunteer PHASE1 COMPLETED 2025-10-11 Madison, Wisconsin, 53704-2523... More >>, United States Less <<
NCT00996892 - Terminated(A recommended Phase... More >> 2 dose and schedule was not identified and the study was terminated before initiation of Stage 2B.) Less << - -
NCT00876122 Non-Hodgkin's Lymphoma, Solid ... More >>Cancers Less << PHASE1 COMPLETED 2025-07-12 Sutton, SM2 5PT, United Kingdo... More >>m Less <<
NCT01918306 Estrogen Receptor Negative Bre... More >>ast Cancer Human Epidermal Growth Factor 2 Negative Carcinoma of Breast Triple Negative Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer Triple-negative Breast Cancer Less << Phase 1 Phase 2 Terminated(company stopped pro... More >>duction of study drug due to excessive toxicities, lack of efficacy) Less << - United States, Alabama ... More >> University of Alabama Birmingham, Alabama, United States United States, California University of California, San Francisco San Francisco, California, United States United States, District of Columbia Georgetown University Washington, D.C., District of Columbia, United States United States, Georgia Emory University Atlanta, Georgia, United States United States, Illinois University of Chicago Chicago, Illinois, United States United States, Indiana Indiana University Indianapolis, Indiana, United States United States, Maryland John Hopkins University Baltimore, Maryland, United States United States, Massachusetts Dana Farber Cancer Institute Boston, Massachusetts, United States United States, Michigan University of Michigan Ann Arbor, Michigan, United States United States, Minnesota Mayo Clinic Rochester, Minnesota, United States United States, New York Memorial Sloan-Kettering Cancer Center New York, New York, United States United States, North Carolina University of North Carolina Charlotte, North Carolina, United States United States, Pennsylvania University of Pittsburgh Pittsburgh, Pennsylvania, United States United States, Tennessee Vanderbilt-Ingram Cancer Center Nashville, Tennessee, United States, 37232 United States, Texas Baylor Breast Center Houston, Texas, United States United States, Washington University of Washington Seattle, Washington, United States Less <<
NCT01740336 Breast Cancer Phase 2 Completed - -
NCT01918306 - Terminated(company stopped pro... More >>duction of study drug due to excessive toxicities, lack of efficacy) Less << - -
NCT00876109 Solid Cancers PHASE1 COMPLETED 2025-11-13 Scottsdale, Arizona, 85258, Un... More >>ited States|Boston, Massachusetts, 02215, United States|Detroit, Michigan, 48201, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.95mL

0.39mL

0.19mL

9.73mL

1.95mL

0.97mL

19.47mL

3.89mL

1.95mL

References

[1]Folkes AJ, Ahmadi K, et al. 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 . J Med Chem. 2008 Sep 25;51(18):5522-32.

[2]Raynaud FI, Eccles SA, et al. 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. Mol Cancer Ther. 2009 Jul;8(7):1725-38.

[3]Salphati L, Shahidi-Latham S, et al. Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. Drug Metab Dispos. 2014 Jul;42(7):1110-6.

[4]Garcia-Martínez JM, Wullschleger S, et al. Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice. Br J Cancer. 2011;104(7):1116-25.

[5]Wallin JJ, Guan J, et al. 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. Clin Cancer Res. 2012;18(14):3901-11.

[6]Burrows N, Babur M, et al. GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1α (HIF-1α) pathways. J Clin Endocrinol Metab. 2011;96(12):E1934-43.

 

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