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

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 Malignant Solid NeoplasmBreast cancer recurrent+ [7]

Originator Organization

Genentech, Inc.

Active Organization

The Institute of Cancer Research: Royal Cancer Hospital

Inactive Organization

Genentech, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

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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250

Literatures (Medical) associated with Pictilisib

31 Dec 2024·Future Science OA

SARS-CoV-2-induced phosphorylation and its pharmacotherapy backed by artificial intelligence and machine learning

Article

Author: Qamar, Fouzia ; Idrees, Jawaria ; Salman, Saad ; Haider, Sana ; Wasim, Asif ; Sharif, Zubair

Aims: To investigate the role of phosphorylation in SARS-CoV-2 infection, potential therapeutic targets and its harmful genetic sequences. Materials & Methods: Data mining techniques were employed to identify upregulated kinases responsible for proteomic changes induced by SARS-CoV-2. Spike and nucleocapsid proteins' sequences were analyzed using predictive tools, including SNAP2, MutPred2, PhD-SNP, SNPs&Go, MetaSNP, Predict-SNP and PolyPhen-2. Missense variants were identified using ensemble-based algorithms and homology/structure-based models like SIFT, PROVEAN, Predict-SNP and MutPred-2. Results: Eight missense variants were identified in viral sequences. Four damaging variants were found, with SNPs&Go and PolyPhen-2. Promising therapeutic candidates, including gilteritinib, pictilisib, sorafenib, RO5126766 and omipalisib, were identified. Conclusion: This research offers insights into SARS-CoV-2 pathogenicity, highlighting potential treatments and harmful variants in viral proteins.

27 Mar 2024·Journal of Immunology Research

Develop a Novel Signature to Predict the Survival and Affect the Immune Microenvironment of Osteosarcoma Patients: Anoikis-Related Genes

Article

Author: Yang, Mingyi ; Xu, Peng ; Su, Yani ; Cai, Yongsong ; Wen, Pengfei ; Yang, Zhi ; Xu, Ke ; Liu, Lin ; Zheng, Haishi

Objective. Osteosarcoma (OS) represents a prevalent primary bone neoplasm predominantly affecting the pediatric and adolescent populations, presenting a considerable challenge to human health. The objective of this investigation is to develop a prognostic model centered on anoikis-related genes (ARGs), with the aim of accurately forecasting the survival outcomes of individuals diagnosed with OS and offering insights into modulating the immune microenvironment. Methods. The study’s training cohort comprised 86 OS patients sourced from The Cancer Genome Atlas database, while the validation cohort consisted of 53 OS patients extracted from the Gene Expression Omnibus database. Differential analysis utilized the GSE33382 dataset, encompassing three normal samples and 84 OS samples. Subsequently, the study executed gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses. Identification of differentially expressed ARGs associated with OS prognosis was carried out through univariate COX regression analysis, followed by LASSO regression analysis to mitigate overfitting risks and construct a robust prognostic model. Model accuracy was assessed via risk curves, survival curves, receiver operating characteristic curves, independent prognostic analysis, principal component analysis, and t-distributed stochastic neighbor embedding (t-SNE) analysis. Additionally, a nomogram model was devised, exhibiting promising potential in predicting OS patient prognosis. Further investigations incorporated gene set enrichment analysis to delineate active pathways in high- and low-risk groups. Furthermore, the impact of the risk prognostic model on the immune microenvironment of OS was evaluated through tumor microenvironment analysis, single-sample gene set enrichment analysis (ssGSEA), and immune infiltration cell correlation analysis. Drug sensitivity analysis was conducted to identify potentially effective drugs for OS treatment. Ultimately, the verification of the implicated ARGs in the model construction was conducted through the utilization of real-time quantitative polymerase chain reaction (RT-qPCR). Results. The ARGs risk prognostic model was developed, comprising seven high-risk ARGs (CBS, MYC, MMP3, CD36, SCD, COL13A1, and HSP90B1) and four low-risk ARGs (VASH1, TNFRSF1A, PIP5K1C, and CTNNBIP1). This prognostic model demonstrates a robust capability in predicting overall survival among patients. Analysis of immune correlations revealed that the high-risk group exhibited lower immune scores compared to the low-risk group within our prognostic model. Specifically, CD8+ T cells, neutrophils, and tumor-infiltrating lymphocytes were notably downregulated in the high-risk group, alongside significant downregulation of checkpoint and T cell coinhibition mechanisms. Additionally, three immune checkpoint-related genes (CD200R1, HAVCR2, and LAIR1) displayed significant differences between the high- and low-risk groups. The utilization of a nomogram model demonstrated significant efficacy in prognosticating the outcomes of OS patients. Furthermore, tumor metastasis emerged as an independent prognostic factor, suggesting a potential association between ARGs and OS metastasis. Notably, our study identified eight drugs—Bortezomib, Midostaurin, CHIR.99021, JNK.Inhibitor.VIII, Lenalidomide, Sunitinib, GDC0941, and GW.441756—as exhibiting sensitivity toward OS. The RT-qPCR findings indicate diminished expression levels of CBS, MYC, MMP3, and PIP5K1C within the context of OS. Conversely, elevated expression levels were observed for CD36, SCD, COL13A1, HSP90B1, VASH1, and CTNNBIP1 in OS. Conclusion. The outcomes of this investigation present an opportunity to predict the survival outcomes among individuals diagnosed with OS. Furthermore, these findings hold promise for progressing research endeavors focused on prognostic evaluation and therapeutic interventions pertaining to this particular ailment.

22 Mar 2024·Oncogene

Simultaneous inhibition of PI3K and PAK in preclinical models of neurofibromatosis type 2-related schwannomatosis

Article

Author: Fernandez-Valle, Cristina ; Nagel, Anna ; Victoria, Berta ; Huegel, Julianne ; Rosario, Rosa ; Hardin, Haley M ; Petrilli, Alejandra

AbstractNeurofibromatosis Type 2 (NF2)-related schwannomatosis is a genetic disorder that causes development of multiple types of nervous system tumors. The primary and diagnostic tumor type is bilateral vestibular schwannoma. There is no cure or drug therapy for NF2. Recommended treatments include surgical resection and radiation, both of which can leave patients with severe neurological deficits or increase the risk of future malignant tumors. Results of our previous pilot high-throughput drug screen identified phosphoinositide 3-kinase (PI3K) inhibitors as strong candidates based on loss of viability of mouse merlin-deficient Schwann cells (MD-SCs). Here we used novel human schwannoma model cells to conduct combination drug screens. We identified a class I PI3K inhibitor, pictilisib and p21 activated kinase (PAK) inhibitor, PF-3758309 as the top combination due to high synergy in cell viability assays. Both single and combination therapies significantly reduced growth of mouse MD-SCs in an orthotopic allograft mouse model. The inhibitor combination promoted cell cycle arrest and apoptosis in mouse merlin-deficient Schwann (MD-SCs) cells and cell cycle arrest in human MD-SCs. This study identifies the PI3K and PAK pathways as potential targets for combination drug treatment of NF2-related schwannomatosis.

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	AR	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	SG	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	CA	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	ES	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	RU	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	HK	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	KR	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	GB	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	PE	Genentech, Inc.	01 Oct 2011
Metastatic breast cancer	Discovery	TH	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


NCT00996892 (Pubmed \| Invest New Drugs) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	177	Cobimetinib+pictilisib	(ykvksmacve) = diarrhea, decreased appetite, hypersensitivity and dehydration. imibvapteo (tyiggdzqxl ) View more	Negative	01 Apr 2020
NCT00960960 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Advanced breast cancer	69	bevacizumab+trastuzumab+pictilisib+paclitaxel	(jsfwwyuyxj) = kcnkdxusyy uywdmhgibu (nfzejnhxmj ) View more	Positive	05 Sep 2018
NCT00975182 (Pubmed \| Oncologist) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	57	Pictilisib+Erlotinib	(exgsotojbw) = 340 mg pictilisib on a "5 days on, 2 days off" schedule plus 100 mg erlotinib bucdiiuygp (wrqhevpxsb ) 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	(lpnqkupren) = 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule lrxsthwztx (mmtoqkvjyz )	Positive	01 Nov 2017
NCT01740336 (PEGGY, Pubmed \| Ann Oncol) Manual	Phase 2	Metastatic HER2-Negative Breast Carcinoma HR positive \| HER2-negative	183	paclitaxel+Pictilisib	(xqhvvzdhsi) = oifqiwkfoo eczpswilxn (upkenmsiup ) View more	Negative	01 Nov 2016
NCT01740336 (PEGGY, Pubmed \| Ann Oncol) Manual	Phase 2		183	paclitaxel+Placebo	(xqhvvzdhsi) = gfymbmxeqp eczpswilxn (upkenmsiup ) View more	Negative	01 Nov 2016
Pubmed \| J Urol	Phase 2	Estrogen receptor positive breast cancer	-	Anastrozole 1 mg	qrprkhgiqv(tqxawpzbwu) = xsqzjcmyie wkyrospzqf (ywcvfnytsh, ≤ 75.4)	-	10 Jun 2016
Pubmed \| J Urol	Phase 2	Estrogen receptor positive breast cancer	-	Anastrozole 1 mg + Pictilisib 260 mg	qrprkhgiqv(tqxawpzbwu) = xzaeqkphao wkyrospzqf (ywcvfnytsh, ≥ 79.0)	-	10 Jun 2016
NCT01493843 (WCLC2015)	Phase 2	Squamous non-small cell lung cancer First line	158	Pictilisib	(jjrsbntmgs) = hfjlunicrl gdoulezdvz (lwpjtdnhxx ) View more	-	09 Sep 2015
NCT01493843 (WCLC2015)	Phase 2	Squamous non-small cell lung cancer First line	158	Placebo	(jjrsbntmgs) = bqjdhzlbgk gdoulezdvz (lwpjtdnhxx ) View more	-	09 Sep 2015
NCT01493843 (WCLC2015)	Phase 2	Non-Small Cell Lung Cancer First line	160	Pictilisib + Carboplatin + Paclitaxel	(auyutemjqy) = nefvacjrnw xqbugnhous (hpioozjgzt ) View more	-	09 Sep 2015
NCT01493843 (WCLC2015)	Phase 2	Non-Small Cell Lung Cancer First line	160	Placebo + Carboplatin + Paclitaxel	(auyutemjqy) = ojmffztean xqbugnhous (hpioozjgzt ) View more	-	09 Sep 2015
NCT00876122 (Pubmed \| Clin Cancer Res) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	60	Pictilisib	(zxmnzgrvur) = grade 1-2 nausea, rash, and fatigue nytzwrrqdd (uuumfctfhc ) View more	Positive	01 Jan 2015
GDC4254g (ASCO2011)	Phase 1	Multiple Myeloma \| HR-positive/HER2-low Solid Tumors	42	GDC-0941	(ztdlzrsosi) = hycgoxebrt ftlnevjybu (gplgfhcbhg ) View more	-	20 May 2011