Delving into the Latest Updates on Pictilisib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Pictilisib (USAN), Pictrelisib

+ [2]

Target

PI3Kα x PI3Kδ

Action

inhibitors

Mechanism

PI3Kα inhibitors(Phosphatidylinositol 3 kinase alpha inhibitors), PI3Kδ inhibitors(Phosphatidylinositol 3 kinase delta inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [5]

Active Indication

Breast CancerGastrointestinal NeoplasmsMelanoma+ [2]

Inactive Indication

Advanced breast cancerAdvanced Lung Non-Small Cell CarcinomaAdvanced Malignant Solid Neoplasm+ [16]

Originator Organization

Genentech, Inc.

Active Organization

The Institute of Cancer Research: Royal Cancer Hospital

Inactive Organization

Genentech, Inc.

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC23H27N7O3S2

InChIKeyLHNIIDJUOCFXAP-UHFFFAOYSA-N

CAS Registry957054-30-7

Part A: This is a phase Ib trial combining the CDK4/6 inhibitor palbociclib with the PI3K inhibitors taselisib, or pictilisib. There are two treatment arms during the dose escalation phase where patients will receive either taselisib OR pictilisib in combination with palbociclib. Palbociclib, taselisib and pictilisib can all be given orally once daily with food, in a 21-days-on and 7-days-off schedule. Once the MTD is reached, the combination with the optimum safety and PK/PD profile will be taken forward to the dose expansion phase (Part B).
Part B1: At the MTD dose expansion, fulvestrant will be administered in addition to palbociclib and taselisib or pictilisib orally once daily, in a 21-days-on and 7-days-off schedule in the ER+ve HER2-ve PIK3CA mutant breast cancer cohort. Fulvestrant will be given intramuscularly on Day 1, Day 15 in cycle one followed by Day 1 for all subsequent cycles.
Part B2: At the MTD dose expansion, patients with PIK3CA mutant advanced solid tumours will be treated with palbociclib and taselisib or pictilisib orally once daily, in a 21-days-on and 7-days-off schedule.

Start Date25 Mar 2015

Sponsor / Collaborator

Royal Marsden NHS Foundation Trust

[+3]

NCT02092831

/ CompletedPhase 1

A PHASE 1, OPEN-LABEL STUDY TO EVALUATE THE EFFECT OF FORMULATION AND TABLET HARDNESS ON THE RELATIVE BIOAVAILABILITY OF PICTILISIB (GDC-0941) IN HEALTHY SUBJECTS

This Phase 1, open-label, randomized, 4-period crossover study is designed to determine the relative bioavailability of GDC-0941 administered as a single dose of the market image formulation at 3 different hardnesses (hardness 1, 2, and 3) and as a single dose of the Phase 2 formulation to healthy male and female volunteers. Participants will be randomly assigned to 4 possible treatment sequences, each comprising 4 periods (1 per formulation), and GDC-0941 will be administered based on the assigned sequence. The study is expected to last 8 weeks.

Start Date01 Apr 2014

Sponsor / Collaborator

Genentech, Inc.

NCT01918306

/ TerminatedPhase 1/2IIT

A Phase Ib/II Trial of GDC-0941 (a PI3K Inhibitor) in Combination With Cisplatin in Patients With Androgen Receptor Negative Triple Negative Metastatic Breast Cancer

This phase I/II trial study evaluates the tolerability and best tolerated dose of the PI3K inhibitor GDC-0941 when given with the chemotherapy cisplatin. This study will also examine how well the combination of GDC-0941 and cisplatin work in treating patients with androgen receptor negative triple negative metastatic breast cancer. Patients will be randomized to receive cisplatin alone or cisplatin with GDC-0941 in the phase II portion. Those receiving cisplatin alone can receive GDC-0941 upon progression of their disease. Cisplatin is a chemotherapy which has been shown to be effective in treating triple negative breast cancer. Preclinical studies show that adding a PI3K inhibitor such as GDC-0941 to cisplatin may be a more effective treatment for breast cancer.

Start Date01 Sep 2013

Sponsor / Collaborator

The Vanderbilt-Ingram Cancer Center

[+2]

100 Clinical Results associated with Pictilisib

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100 Translational Medicine associated with Pictilisib

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100 Patents (Medical) associated with Pictilisib

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692

Literatures (Medical) associated with Pictilisib

01 Apr 2025·Bioorganic & Medicinal Chemistry

Thienopyrimidine: A promising scaffold in the development of kinase inhibitors with anticancer activities

Review

Author: Jin, Cheng-Yun ; Du, Yi-Fei ; Liu, Yun-He ; Wang, Zi-Yue ; Zhang, Sai-Yang ; Niu, Jin-Bo ; Song, Jian ; Liu, Xuan-Han

Protein kinases represent a highly promising drug target, with over 80 drugs that target about two dozen different protein kinases have been approved by the US FDA, particularly in cancer treatment. Over the past decades, the unique structural characteristics of the thienopyrimidine ring system provide an adaptive platform for designing potent anticancer agents, especially various kinase inhibitors, which has attracted widespread attention. Some of these thienopyrimidines as anticancer kinase inhibitors have already been marketed or are currently undergoing clinical/preclinical studies for the treatment of cancers, such as Olmutinib, Pictilisib, SNS-314, PF-03758309, and Fimepinostat, highlighting the substantial advantages of the thienopyrimidine scaffold in the discovery of anticancer agents. This article reviews the discovery, activity, and structure-activity relationships of antitumor kinase inhibitors based on the thienopyrimidine scaffold, and partially discusses the binding modes between thienopyrimidine derivatives and their kinase targets. By elucidating the application of thienopyrimidine derivatives as anticancer kinase inhibitors, this review aims to provide new perspectives for the development of more effective and novel kinase inhibitors.

01 Mar 2025·Nature Chemical Biology

A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery

Article

Author: Raivola, Juuli ; Piki, Emilia ; Ungureanu, Daniela ; Murumägi, Astrid ; Sharma, Subodh ; Dini, Alice ; Barker, Harlan

AbstractThe gene-regulatory dynamics governing drug responses in cancer are yet to be fully understood. Here, we report a pipeline capable of producing high-throughput pharmacotranscriptomic profiling through live-cell barcoding using antibody–oligonucleotide conjugates. This pipeline combines drug screening with 96-plex single-cell RNA sequencing. We show the potential of this approach by exploring the heterogeneous transcriptional landscape of primary high-grade serous ovarian cancer (HGSOC) cells after treatment with 45 drugs, with 13 distinct classes of mechanisms of action. A subset of phosphatidylinositol 3-OH kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) inhibitors induced the activation of receptor tyrosine kinases, such as the epithelial growth factor receptor (EGFR), and this was mediated by the upregulation of caveolin 1 (CAV1). This drug resistance feedback loop could be mitigated by the synergistic action of agents targeting PI3K–AKT–mTOR and EGFR for HGSOC with CAV1 and EGFR expression. Using this workflow could enable the personalized testing of patient-derived tumor samples at single-cell resolution.

18 Feb 2025·Oncogene

Unveiling RACK1: a key regulator of the PI3K/AKT pathway in prostate cancer development

Article

Author: Pradeep, Anirudh ; Lyu, Cancan ; Vaddi, Prasanna Kuma ; Elshafae, Said ; Chen, Songhai ; Ma, Deqin

The dysregulated PI3K/AKT pathway is pivotal in the onset and progression of various cancers, including prostate cancer. However, targeting this pathway directly poses challenges due to compensatory upregulation of alternative oncogenic pathways. This study focuses on the novel regulatory activity of the Receptor for Activated Protein Kinase (RACK1), a scaffolding/adaptor protein, in governing the PI3K/AKT pathway within prostate cancer. Through a genetic mouse model, our research unveils RACK1's pivotal role in orchestrating AKT activation and the genesis of prostate cancer. RACK1 deficiency hampers AKT activation, effectively impeding prostate tumor formation induced by PTEN and p53 deficiency. Mechanistically, RACK1 facilitates AKT membrane translocation and fosters its interaction with mTORC2, thereby promoting AKT activation and subsequent tumor cell proliferation and tumor formation. Notably, inhibiting AKT activation via RACK1 deficiency does not trigger feedback upregulation of HER3 and androgen receptor (AR) expression and activation, distinguishing it from direct PI3K or AKT targeting. These findings position RACK1 as a critical regulator of the PI3K/AKT pathway and a promising target for curtailing prostate cancer development arising from pathway aberrations.

100 Deals associated with Pictilisib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10189	Pictilisib	-	DB11663

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic breast cancer	Discovery	Denmark	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	Czechia	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	Belgium	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	France	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	Canada	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	Argentina	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	Germany	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	Mexico	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	United States	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	Malaysia	Genentech, Inc.	01 Oct 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


OPPORTUNE (SABCS2023)	Phase 2	Estrogen receptor positive breast cancer HER2-negative \| Ki67 \| MYBL2	124	Anastrozole 1 mg	nvfjhebrny(macggemqxv) = sspxjkumzu kiviglxdeh (hycdgxizuz )	Positive	01 Mar 2023
				Pictilisib 260 mg + Anastrozole 1 mg	nvfjhebrny(macggemqxv) = lnszzumgtz kiviglxdeh (hycdgxizuz )
NCT00996892 (Pubmed \| Invest New Drugs) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	177	Cobimetinib+pictilisib	(vtgmbcrtsd) = diarrhea, decreased appetite, hypersensitivity and dehydration. rwcgpppbom (svcqhckfpw ) View more	Negative	01 Apr 2020
P2-08-02 (SABCS2019)	Phase 2	Estrogen receptor positive breast cancer PIK3CA mutation subclasses \| Ki-67 protein expression \| Caspase3 ... View more	167	Anastrozole 1 mg	imyyvktvwr(oggvkvpkjq) = nncazyuwzp cclmiitlwr (ejsoyxprvf, 61.0 - 78.0)	Positive	15 Feb 2019
				Anastrozole 1 mg + Pictilisib 260 mg	imyyvktvwr(oggvkvpkjq) = eowtepbizn cclmiitlwr (ejsoyxprvf, 78.3 - 85.8)
NCT00960960 (Pubmed \| Clin Cancer Res \| Breast Cancer Res) Manual	Phase 1	Advanced breast cancer	69	bevacizumab+trastuzumab+pictilisib+paclitaxel	(zizbvmoyow) = umlfrszark fsfowizsfc (cttzilaypf ) View more	Positive	05 Sep 2018
NCT00975182 (Pubmed \| Oncologist) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	57	Pictilisib+Erlotinib	(rqnfrgqfgw) = 340 mg pictilisib on a "5 days on, 2 days off" schedule plus 100 mg erlotinib xgxryaaoog (lokfdqodgq ) View more	Positive	01 Dec 2017
NCT00974584 (Pubmed \| Eur J Cancer Care (Engl)) Manual	Phase 1	Non-Small Cell Lung Cancer	66	paclitaxel+carboplatin+pemetrexed+cisplatin+bevacizumab+pictilisib	(xxzufzhrhm) = 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule ehlwtweyze (iioxfreqkh )	Positive	01 Nov 2017
NCT01740336 (PEGGY, Pubmed \| Ann Oncol) Manual	Phase 2	Metastatic HER2-Negative Breast Carcinoma HR positive \| HER2-negative	183	paclitaxel+Pictilisib	(zfmhjijlfo) = ssaxiigvhe mgximelwei (tjadthoyll ) View more	Negative	01 Nov 2016
				paclitaxel+Placebo	(zfmhjijlfo) = kieesleals mgximelwei (tjadthoyll ) View more
ISRCTN26131497 (Pubmed \| J Clin Oncol)	Phase 2	Estrogen receptor positive breast cancer PIK3CA mutations \| molecular subtype	-	Anastrozole 1 mg	xokrbkijrx(xazhhwlkqx) = ieufcydemx rcfqhoszqa (meojfyzrpg, ≤ 75.4)	-	10 Jun 2016
				Anastrozole 1 mg + Pictilisib 260 mg	xokrbkijrx(xazhhwlkqx) = qylrczbrei rcfqhoszqa (meojfyzrpg, ≥ 79.0)
NCT01437566 (FERGI, SABCS2016)	Phase 2	Metastatic breast cancer \| Advanced breast cancer ESR1 mutations \| PIK3CA mutations	168	Fulvestrant + Placebo	(mtxbcwpfds) = euvrjfkcok tpwgrcgjus (iowluzybkn )	Negative	15 Feb 2016
				Fulvestrant + Pictilisib	(mtxbcwpfds) = awbgxrbicz tpwgrcgjus (iowluzybkn )
NCT01493843 (WCLC2015)	Phase 2	Non-Small Cell Lung Cancer First line	160	Pictilisib + Carboplatin + Paclitaxel	(ihqmjizefz) = okgttlhxfd gzpmqpunyb (kgvcepgohq ) View more	-	09 Sep 2015
				Placebo + Carboplatin + Paclitaxel	(ihqmjizefz) = pzptckfmth gzpmqpunyb (kgvcepgohq ) View more