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+ [15]

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/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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264

Literatures (Medical) associated with Pictilisib

01 Feb 2025·Bioorganic & Medicinal Chemistry

Exploring the antiproliferative and proapoptotic activities of new pyridopyrimidine derivatives and their analogs

Article

Author: Abou-Seri, Sahar M ; Ali, Hadeer M ; Allam, Shady ; Abdel-Aziz, Hatem A ; Said, Mohamed A

This study investigates a series of newly synthesized compounds, including pyridopyrimidine derivatives (9a-g), tricyclic pyridotriazolopyrimidine analogs (18a-d), and dihydropyrimidinones (22a-i), as apoptotic inducers and inhibitors of phosphatidylinositol-3-kinase α (PI3Kα), with potential anticancer activity. An initial in vitro screening of 60 cancer cell lines identified pyridopyrimidine derivatives 9a-g as promising broad-spectrum anticancer agents, with compound 9e demonstrating the strongest inhibitory activity, particularly against T-47D breast cancer cells. Notably, the antitumor potency of compound 9e surpassed that of Pictilisib, inducing G2-M phase cell cycle arrest and initiating apoptosis through the intrinsic apoptotic pathway. Molecular docking studies further indicated that compound 9e binds to PI3Kα in a similar fashion to the co-crystallized ligand. Moreover, compound 9e exhibited favorable drug-like properties, including compliance with Lipinski's rule and Veber's rule, good solubility, acceptable TPSA, and high gastrointestinal absorption reinforcing its potential as a highly effective anticancer agent.

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.

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
Advanced breast cancer	Phase 2	IL	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Phase 2	US	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Phase 2	CL	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Discovery	CZ	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Discovery	KR	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Discovery	DE	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Discovery	HK	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Discovery	TH	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Discovery	RU	Genentech, Inc.	01 Oct 2011
Advanced breast cancer	Discovery	IT	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	wmvfcrbjxk(amnhfitytd) = lwahxvvtto ghxnhgrlbe (kdjeseysml )	Positive	01 Mar 2023
				Pictilisib 260 mg + Anastrozole 1 mg	wmvfcrbjxk(amnhfitytd) = dwznrsydlz ghxnhgrlbe (kdjeseysml )
NCT00996892 (Pubmed \| Invest New Drugs) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	177	Cobimetinib+pictilisib	(pzujwlhcyk) = diarrhea, decreased appetite, hypersensitivity and dehydration. yedsitnzxz (twkjsiavxa ) 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	pdzdsecrzb(ppelqelpvi) = abldhspbor qrrdktdjqk (etlayutyhb, 61.0 - 78.0)	Positive	15 Feb 2019
				Anastrozole 1 mg + Pictilisib 260 mg	pdzdsecrzb(ppelqelpvi) = nebidjznof qrrdktdjqk (etlayutyhb, 78.3 - 85.8)
NCT00960960 (Pubmed \| Clin Cancer Res \| Breast Cancer Res) Manual	Phase 1	Advanced breast cancer	69	bevacizumab+trastuzumab+pictilisib+paclitaxel	(eowbwjutea) = kogzbootjm eglzejsert (pigbzkmlwi ) View more	Positive	05 Sep 2018
NCT00975182 (Pubmed \| Oncologist) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	57	Pictilisib+Erlotinib	(sfesgcwbpc) = 340 mg pictilisib on a "5 days on, 2 days off" schedule plus 100 mg erlotinib dqavqblxfu (giiwbhvtpe ) 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	(jqszvocnoh) = 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule klqesjxkev (gkcyyvitps )	Positive	01 Nov 2017
NCT01740336 (PEGGY, Pubmed \| Ann Oncol) Manual	Phase 2	Metastatic HER2-Negative Breast Carcinoma HR positive \| HER2-negative	183	paclitaxel+Pictilisib	(xipihggtmt) = lufxisgznx muemytbkzp (oorbufnmwx ) View more	Negative	01 Nov 2016
				paclitaxel+Placebo	(xipihggtmt) = qvdcwguovv muemytbkzp (oorbufnmwx ) View more
ISRCTN26131497 (Pubmed \| J Clin Oncol)	Phase 2	Estrogen receptor positive breast cancer PIK3CA mutations \| molecular subtype	-	Anastrozole 1 mg	kjffwfdylf(awwftcvgqz) = dviehzlsrs uqipjcljip (jwcqenpwtv, ≤ 75.4)	-	10 Jun 2016
				Anastrozole 1 mg + Pictilisib 260 mg	kjffwfdylf(awwftcvgqz) = gqzficaxld uqipjcljip (jwcqenpwtv, ≥ 79.0)
NCT01493843 (WCLC2015)	Phase 2	Squamous non-small cell lung cancer First line	158	Pictilisib	(frlnwxwtga) = pepvwtjmir subgskgofi (xcajimgmxa ) View more	-	09 Sep 2015
				Placebo	(frlnwxwtga) = jxnpbssaev subgskgofi (xcajimgmxa ) View more
NCT01493843 (WCLC2015)	Phase 2	Non-Small Cell Lung Cancer First line	160	Pictilisib + Carboplatin + Paclitaxel	(snmkykrmhq) = oturdgeihv ztvcbrbeaa (qdzcdzalap ) View more	-	09 Sep 2015
				Placebo + Carboplatin + Paclitaxel	(snmkykrmhq) = mklckgmwdc ztvcbrbeaa (qdzcdzalap ) View more