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67 Companies | 59 Products |
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59 Products | |
344 Diseases | |
343 Trials |  |
12261 News |  |
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- | dactolisib (RTB101) / resTORbio
Preclinical, Journal: Topical application of a dual PI3K/mTOR inhibitor prevents anal carcinogenesis in a human papillomavirus mouse model of anal cancer. (Pubmed Central) - Jul 29, 2020
Compared with no-treatment mice, both BEZ235-treated and DMBA+BEZ235-treated mice had significantly higher LC3β expression, signifying autophagic induction (P<0.01), whereas DMBA-treated, BEZ235-treated, and DMBA+BEZ235-treated mice had a significantly lower p62 expression, signifying active autophagy (P<0.0005). In conclusion, consistent with systemic delivery, topical application of BEZ235 shows decreased anal carcinogenesis through the activation of autophagy.
- | Journal: MicroRNA-4286 promotes cell proliferation, migration, and invasion via PTEN regulation of the PI3K/Akt pathway in non-small cell lung cancer. (Pubmed Central) - Jul 29, 2020
Taken together, our findings elucidate that miR-4286 promotes the tumorigenesis of NSCLC by interacting with PTEN. This miR-4286-mediated upregulation of PTEN might lead to new therapeutic strategies for NSCLC.
- | Journal: Human bone-marrow derived mesenchymal stem cells home via the PI3K-Akt, MAPK, and Jak/Stat signaling pathways in response to PDGF. (Pubmed Central) - Jul 29, 2020
These findings showed that MSC homing may be driven by activation of PDGFRA/PI3K/Akt, PDGFRA/MAPK/Grb2 and PDGFRA/Jak2/Stat signaling, as a result of SDF-1 stimulated endothelial cell production of PDGF. This model can be used to further investigate these key regulatory molecules towards development of targeted therapies.
- | Journal, IO Biomarker: Metabolic stress in cancer cells induces immune escape through a PI3K-dependent blockade of IFNγ receptor signaling. (Pubmed Central) - Jul 29, 2020
This model can be used to further investigate these key regulatory molecules towards development of targeted therapies. These data revealed a strong impact of metabolic stress on the presentation of tumor antigens by MHC class I and suggest that this type of tumor escape takes place at hypoxic areas even during times of active T cell immunity and IFNy release.
- | ME-401 / MEI, Kyowa Hakko Kirin, VetDC, umbralisib (TGR-1202) / TG Therap
Review, Journal: Exploring a Future for PI3K Inhibitors in Chronic Lymphocytic Leukemia. (Pubmed Central) - Jul 29, 2020
Furthermore, alternative dosing schedules may reduce toxicities of these agents. Inhibition of PI3K remains an important strategy in management of CLL and novel approaches to limit toxicities of PI3K inhibitors represent an important area of clinical research in CLL.
- ||| Clinical: https://t.co/ZOD0NI9B3g Suppression of insulin feedback enhances the efficacy of PI3K inhibitors (Twitter) - Jul 29, 2020
- | Journal: PI3K Catalytic Subunits α and β Modulate Cell Death and IL-6 Secretion Induced by Talc Particles in Human Lung Carcinoma Cells. (Pubmed Central) - Jul 29, 2020
Our results suggest a novel role of the PI3K pathway in talc-induced cell death and IL-6 secretion in lung carcinoma cells. These cellular events are known to drive fibrosis, and thus further studies of the PI3K pathway may provide a better understanding of the mechanisms of talc sclerosis in the malignant pleural space.
- | Journal: MicroRNA-939-5p directly targets IGF-1R to inhibit the aggressive phenotypes of osteosarcoma through deactivating the PI3K/Akt pathway. (Pubmed Central) - Jul 29, 2020
The present study demonstrated that miR‑939 exerted tumor‑suppressing roles in the malignancy of OS cells by directly targeting IGF‑1R and inactivating the PI3K/AKT pathway. Therefore, this miRNA may be a promising target for anticancer therapy in patients with OS.
- | fimepinostat (CUDC-907) / Curis
Preclinical, Journal: CUDC‑907 reverses pathological phenotype of keloid fibroblasts in vitro and in vivo via dual inhibition of PI3K/Akt/mTOR signaling and HDAC2. (Pubmed Central) - Jul 29, 2020
CUDC‑907 not only inhibited AKT and mTOR phosphorylation and promoted the acetylation of histone H3, but also significantly inhibited the phosphorylation levels of Smad2/3 and Erk. These preclinical data demonstrating its anti‑keloid effects suggest that CUDC‑907 may represent a candidate drug for systemic keloid therapy.
- | Journal: Delicaflavone induces ROS-mediated apoptosis and inhibits PI3K/AKT/mTOR and Ras/MEK/Erk signaling pathways in colorectal cancer cells. (Pubmed Central) - Jul 29, 2020
In summary, these results indicated DLF induced ROS-mediated cell cycle arrest and apoptosis through ER stress and mitochondrial pathway accompanying with the inhibition of PI3K/AKT/mTOR and Ras/MEK/Erk signaling cascade. Thus DLF could be a potential therapeutic agent for CRC.
- | quercetin (LY294002) / Eli Lilly
Journal: FAM60A, increased by Helicobacter pylori, promotes proliferation and suppresses apoptosis of gastric cancer cells by targeting the PI3K/AKT pathway. (Pubmed Central) - Jul 29, 2020
We also found that the PI3K/AKT pathway inhibitor LY294002 could revert the changes caused by FAM60A upregulation in HGC-27 and AGS cells. Thus, our study provides evidence that FAM60A act as a carcinogen and suggests that H. pylori-induced upregulation of FAM60A may contribute to the development of gastric cancer.
- | so PI3K is de-novo? on (Twitter) - Jul 29, 2020
- | Journal: Optimization of Orally Bioavailable PI3Kδ Inhibitors and Identification of Vps34 as a key off-target activity. (Pubmed Central) - Jul 29, 2020
Selectivity profiling of compound 19 showed similar potency for the class III PI3K, Vps34, as for PI3Kδ and compound 19 was not well-tolerated in a 7 day rat toxicity study. Structure-based design led to an improvement in selectivity for PI3Kδ over Vps34 and a focus on oral PK properties resulted in the discovery of compound 41, which showed improved toxicological outcomes at similar exposures to compound 19.
- | quercetin (LY294002) / Eli Lilly
Journal: Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype. (Pubmed Central) - Jul 29, 2020
Together, our data indicated that hUC-MSCs can skew macrophages into an M2 phenotype via affecting AKT pathway. These data may provide a new insight into the mechanisms of hUC-MSCs in the therapy of SS dry eye.
- | Journal: Knockdown of TBRG4 suppresses proliferation, invasion and promotes apoptosis of osteosarcoma cells by downregulating TGF-β1 expression and PI3K/AKT signaling pathway. (Pubmed Central) - Jul 29, 2020
By examining the expression levels of TGF-β1, p-PI3K, PI3K, p-AKT and AKT, it showed that the suppression of TBRG4 would reduce TGF-β1 expression and inactivate the PI3K/AKT signaling pathway. These results showed for the first time that TBRG4 knockdown could suppress osteosarcoma progression, suggesting TBRG4 might be a promising therapeutic target for osteosarcoma treatment.
- || Clinical, Journal: Successful Sirolimus Treatment for Korean Patients with Activated Phosphoinositide 3-kinase δ Syndrome 1: the First Case Series in Korea. (Pubmed Central) - Jul 29, 2020
We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.
- | Journal: Daucosterol linolenate from Sweet Potato Suppresses MCF7-Xenograft-Tumor Growth through Regulating PI3K/AKT Pathway. (Pubmed Central) - Jul 29, 2020
DLA also down-regulated the expression of phosphoinositide 3-kinase/protein kinase B and repressed insulin-induced phosphoinositide 3-kinase/protein kinase B activation. Our findings suggest that DLA suppresses breast tumor growth through inactivating the phosphoinositide 3-kinase/protein kinase B pathway.
- | Journal: MicroRNA-29 targets FGF2 and inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway. (Pubmed Central) - Jul 29, 2020
The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18186.
- | Journal: MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway. (Pubmed Central) - Jul 29, 2020
The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14179.
- | ZSTK474 / Zenyaku Kogyo, ATG-017 / Antengene
Journal: Targeting the MAPK/ERK and PI3K/AKT Signaling Pathways Affects NRF2, Trx and GSH Antioxidant Systems in Leukemia Cells. (Pubmed Central) - Jul 28, 2020
However, distinct cell line dependent effects were observed. In conclusion, the combination of AZD0364 and ZSTK474 can exert a synergistic anticancer effect in ALL and AML cells, which is associated with the induction of oxidative stress and the involvement of cellular antioxidant defense mechanisms.
- | buparlisib (BKM120) / Novartis, Adlai Nortye
Journal: A high-throughput drug combination screen identifies an anti-glioma synergism between TH588 and PI3K inhibitors. (Pubmed Central) - Jul 28, 2020
A Sensitivity Index (SI)-based drug combination screening method was established to evaluate the interactions between BKM120, a pan-PI3K inhibitor, and compounds from a library of 606 target-selective inhibitors...Finally, activation of PI3K or overexpression of AKT compromised the anti-glioma efficacy of TH588. The screening method developed in this study demonstrated its usefulness in the rapid identification of synergistic drug combinations of PI3K inhibitors and targeted agents.
- | low molecular weight dextran sulfate (ILB) / TikoMed
Journal: Effect of Sishen Pill on Memory T Cells From Experimental Colitis Induced by Dextran Sulfate Sodium. (Pubmed Central) - Jul 28, 2020
Furthermore, SSP markedly inhibited activation of PI3K, Akt, phospho-Akt, Id2, T-bet, forkhead box O3a, Noxa, and C-myc proteins in the PI3K/Akt signaling pathway and activated Rictor, Raptor, tuberous sclerosis complex (TSC)1, TSC2, phospho-AMP-activated kinase (AMPK)-α, AMPK-α, eukaryotic translation initiation factor 4E-binding protein 2, kinesin family member 2a, and 70-kDa ribosomal protein S6 kinase. These results indicate that SSP effectively controls Tem cells in the peripheral blood to relieve experimental colitis induced by DSS, which were potentially related with inhibiting the PI3K/Akt signaling pathway.
- | Preclinical, Journal, IO Biomarker: Antidiabetic Effects of Arginyl-Fructosyl-Glucose, a Nonsaponin Fraction from Ginseng Processing in Streptozotocin-Induced Type 2 Diabetic Mice through Regulating the PI3K/AKT/GSK-3β and Bcl-2/Bax Signaling Pathways. (Pubmed Central) - Jul 28, 2020
In addition, we demonstrated that AFG also attenuates apoptosis and insulin secretion disorders in T2DM by adjusting the PI3K/AKT/GSK3β signaling pathway. At the end, these discoveries recommend that AFG averts the development of T2DM through numerous types of machinery and proposes that AFG can also be used in order to treat T2DM in the future.
- | quercetin (LY294002) / Eli Lilly
Preclinical, Journal: MicroRNA-221 Modulates Airway Remodeling via the PI3K/AKT Pathway in OVA-Induced Chronic Murine Asthma. (Pubmed Central) - Jul 28, 2020
A PI3K/AKT-inhibitor (LY294002) was used to confirm the role of the pathway in ASMCs...Bioinformatics analysis and western blot analysis confirmed that the PI3K-AKT pathway was involved in ECM deposition in ASMCs. miR-221 might play a crucial role in the mechanism of remodeling via the PI3K/AKT pathway in chronic asthma and it could be considered as a potential target for developing therapeutic strategies.
- | Journal: The anticancer activities of Vernonia amygdalina Delile. Leaves on 4T1 breast cancer cells through phosphoinositide 3-kinase (PI3K) pathway. (Pubmed Central) - Jul 28, 2020
EAF induced early and late apoptosis, inhibited cell cycle progression on the G/M phase, and inhibited PI3K and mTOR expression. The EAF of Vernonia amygdalina Delile leaves showed anticancer activity on 4T1 breast cancer cells through induction of apoptosis, enhanced cell accumulation on G/M phases in the cell cycle, and inhibited expression of PI3K and mTOR.
- | cisplatin / Generic mfg.
Journal: Curcumol improves cisplatin sensitivity of human gastric cancer cells through inhibiting PI3K/AKT pathway. (Pubmed Central) - Jul 28, 2020
The EAF of Vernonia amygdalina Delile leaves showed anticancer activity on 4T1 breast cancer cells through induction of apoptosis, enhanced cell accumulation on G/M phases in the cell cycle, and inhibited expression of PI3K and mTOR. The findings in the current research demonstrated that curcumol could promote the sensitivity of gastric cancer cells to cisplatin-based chemotherapies via inhibiting the phosphatidylinositol 3-kinase (PI3K)/Protein Kinase B (AKT) pathway.
- ||| Lynparza (olaparib) / Merck (MSD), AstraZeneca
Indeed we are in a grey area here. Given the low (<1.5%) prevalence of BRIP1m in Ca Pancr, data is scarce. Olaparib is arguably an option, and @Dr_R_Kurzrock correctly points to potential benefit of downstream MEK blockade. Cross-talk with PI3K pathway is also known. (Twitter) - Jul 28, 2020
- | The usual Sunday list of #PI3K research-relevant papers (including methods and beyond) - thanks to @BiomedNew ! - https://t.co/y2jzf1Rp6B (Twitter) - Jul 26, 2020
- [VIRTUAL] Dihyrosphingosine 1 Phosphate Mediates Collagen Synthesis in Cardiac Fibroblasts Throught Pi3k/akt- Mtor Signalling Pathway () - Jul 26, 2020 - Abstract #BCVS2020BCVS_232;
Conclusion Our study demonstrates for the first time that dhS1P can cause cardiac cellular fibrosis via PI3K/Akt- mTOR pathway. Its inhibition may represent a novel therapeutic strategy for cardiac fibrosis.
- |||||| VS-5584 / Verastem, CCT128930 / Otsuka
CCT128930 enhanced the #anticancer effect of VS-5584 (#PI3K #mTOR) in human #osteosarcoma cells #bone #cancer #health @VerastemOncolog @NIH @NCIResearchCtr @OncoAlert @myESMO @FDAOncology @NCIDirector @NIHDirector @DrWoodcockFDA @SteveFDA @JTrentMDPhD https://t.co/vFGQnnmKkm (Twitter) - Jul 26, 2020
- |||| VS-5584 / Verastem, VS-6766 / Verastem, SCH772984 / Otsuka
Clinical: Or PI3K mTOR VS-5584 in combo, but in clinical study I would switch ERK SCH772984 inhibitor here, with RO5126766 (RAS/RAF/MEK/ERK) https://t.co/wEVbnkwzXa (Twitter) - Jul 25, 2020
- | quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Prolonged high-glucose exposure decreased SREBP-1/FASN/ACC in Schwann cells of diabetic mice via blocking PI3K/Akt pathway. (Pubmed Central) - Jul 25, 2020
LY294002 suppressed Akt activation followed by the decreased SREBP-1, FASN, ACC, triglyceride, and cholesterol...The knockdown of SREBP-1 by shRNA prevented insulin-induced enhanced FASN, ACC mRNA expression, triglyceride, and cholesterol in high-glucose-treated RSC96 cells. In conclusion, prolonged high-glucose exposure inhibits the SREBP-1/FASN/ACC expression in the Schwann cells of DPN via the blockage of the PI3K/Akt signaling pathway.
- | Journal: MicroRNA-1258, regulated by c-Myb, inhibits growth and epithelial-to-mesenchymal transition phenotype via targeting SP1 in oral squamous cell carcinoma. (Pubmed Central) - Jul 25, 2020
In addition, miR-1258 inhibited PI3K/AKT and ERK signalling pathway activity. Taken together, these findings demonstrated that miR-1258 may function as a tumour-suppressive micorRNA in OSCC and suggested that miR-1258 may be a potential therapeutic target for OSCC patients.
- | Preclinical, Journal: Matrine attenuates high-fat diet-induced in vivo and ox-LDL-induced in vitro vascular injury by regulating the PKCα/eNOS and PI3K/Akt/eNOS pathways. (Pubmed Central) - Jul 25, 2020
Moreover, the protective effects of matrine were significantly abolished by the simultaneous application of PKCα and the PI3K inhibitor. Matrine may thus be potentially employed as a novel therapeutic strategy against high-fat diet-induced vascular injury.
- | Journal: Down-regulated lncRNA SLC25A5-AS1 facilitates cell growth and inhibits apoptosis via miR-19a-3p/PTEN/PI3K/AKT signalling pathway in gastric cancer. (Pubmed Central) - Jul 25, 2020
Moreover, it could act as a ceRNA to regulate cellular behaviours via miR-19a-3p/PTEN/PI3K/AKT signalling pathway. Thus, SLC25A5-AS1 might be served as a potential target for cancer therapeutics in GC.
- | Journal: Role of the PI3K/AKT (mTOR and GSK3β) signalling pathway and photobiomodulation in diabetic wound healing. (Pubmed Central) - Jul 25, 2020
However, cellular and molecular mechanisms induced by PBM are not fully understood. In this review we discuss PBM and the PI3K/AKT pathway with specific focus on the mTOR and GSK3β downstream activity in diabetic wound healing.
- || Arzerra (ofatumumab) / Novartis, Genmab, Zydelig (idelalisib) / Gilead
Clinical, P2 data, Journal: Efficacy results of a phase 2 trial of first-line idelalisib plus ofatumumab in chronic lymphocytic leukemia. (Pubmed Central) - Jul 25, 2020
P2
Future development of PI3K inhibitors for use in treatment-naïve CLL will require novel approaches to mitigate toxicities. This trial was registered at www.clinicaltrials.gov as #NCT02135133.
- | sirolimus / Generic mfg.
Journal: Insulin-Like Growth Factor Binding Protein-Related Protein 1 Activates Primary Hepatic Stellate Cells via Autophagy Regulated by the PI3K/Akt/mTOR Signaling Pathway. (Pubmed Central) - Jul 25, 2020
This trial was registered at www.clinicaltrials.gov as #NCT02135133. Autophagy was induced in IGFBPrP1-treated primary HSCs, and IGFBPrP1-induced autophagy promoted the activation of HSCs and extracellular matrix expression, the underlying mechanism of which may involve the phosphatidylinositide 3-kinase/Akt/mTOR signaling pathway.
- | pentylenetetrazole (BTD-001) / Balance Therap, quercetin (LY294002) / Eli Lilly
Journal: Anticonvulsant action of a selective phosphatidylinositol-3-kinase inhibitor LY294002 in pentylenetetrazole-mediated convulsions in zebrafish. (Pubmed Central) - Jul 25, 2020
The mRNA levels of PIK3CA, PIK3R1, AKT1, mTOR, Rps6 and Rps6kb1 in adult zebrafish brain was significantly reduced as compared to vehicle control group. Our results provided conclusive support for the anticonvulsant potential of LY294002.
- | PX-478 / Seattle Genetics
Journal: Triiodothyronine potentiates angiogenesis-related factor expression through PI3K/AKT signaling pathway in human osteoarthritic osteoblasts. (Pubmed Central) - Jul 24, 2020
Additionally, VEGF and p-AKT expression was down-regulated when PX-478 inhibited HIF-1α protein. Our results suggested that local T3 could effectively increase angiogenesis-related factor expression by PI3K/AKT signaling pathway, and HIF-1α regulated the VEGF expression in OA osteoblasts.
- [VIRTUAL] A pan-cancer analysis of double PIK3CA mutations (On-Demand) - Jul 24, 2020 - Abstract #ESMO2020ESMO_2683;
Legal entity responsible for the study: The authors. Funding: NIH R21 CA223789, Susan G. Komen Career Catalyst Research Grant, Fund for Innovation in Cancer Informatics.
- [VIRTUAL] Clinical relevance of somatic and germline alterations in patients with pancreatic ductal adenocarcinoma (On-Demand) - Jul 24, 2020 - Abstract #ESMO2020ESMO_2318;
Legal entity responsible for the study: The authors. Funding: Has not received any funding.
- Ibrance (palbociclib) / Pfizer, Kisqali (ribociclib) / Novartis
[VIRTUAL] Ki67 expression and CDK4/6i activity: An emerging role for PIK3CA mutations in metastatic breast cancer patients (On-Demand) - Jul 24, 2020 - Abstract #ESMO2020ESMO_1496;
Funding: Has not received any funding. Clinical trial identification: Circus study - ID 5694.
- | Journal: Upregulation of lncRNA FER1L4 suppresses the proliferation and migration of the hepatocellular carcinoma via regulating PI3K/AKT signal pathway. (Pubmed Central) - Jul 22, 2020
Clinical trial identification: Circus study - ID 5694. Our study suggested that FER1L4 might alleviate progression of hepatocellular carcinoma via blocking PI3K/AKT pathway, which encourages a better understanding of the pathogenesis of HCC and may provide a novel potential therapeutic target for clinical treatment.
- | vinblastine / Generic mfg.
Journal: Theaflavin and epigallocatechin-3-gallate synergistically induce apoptosis through inhibition of PI3K/Akt signaling upon depolymerizing microtubules in HeLa cells. (Pubmed Central) - Jul 22, 2020
We have shown that synergistic activity might be due to stronger microtubule depolymerization by simultaneous binding of TF and EGCG at different sites on tubulin: TF binds at vinblastine binding site on tubulin, and EGCG binds near colchicines binding site on tubulin. A detailed mechanistic analysis revealed that stronger microtubule depolymerization caused effective downregulation of PI3K/Akt signaling and potently induced mitochondrial apoptotic signals, which ultimately resulted in the apoptotic death of HeLa cells in a synergistic manner.
- | sirolimus / Generic mfg.
Journal, PD(L)-1 Biomarker, IO Biomarker: The effect of LKB1 activity on the sensitivity to PI3K/mTOR inhibition in non-small cell lung cancer. (Pubmed Central) - Jul 22, 2020
A detailed mechanistic analysis revealed that stronger microtubule depolymerization caused effective downregulation of PI3K/Akt signaling and potently induced mitochondrial apoptotic signals, which ultimately resulted in the apoptotic death of HeLa cells in a synergistic manner. Dual molecular targeted therapy for mTOR and PI3K may be a promising therapeutic strategy in the specific population of lung cancer patients with LKB1 loss.
- | metformin / Generic mfg., Sutent (sunitinib) / Pfizer
Preclinical, Journal: Upregulation of phosphoinositide 3-kinase prevents sunitinib-induced cardiotoxicity in vitro and in vivo. (Pubmed Central) - Jul 22, 2020
In summary, our data indicate that increased PI3K activity is protective against SNT-induced calcium mishandling and contractile dysfunction. Cardiac-specific PI3K activation could be an effective therapeutic approach to treat SNT cardiotoxicity in patients with cancer.
- | Preclinical, Journal: Oxymatrine protects neonatal rat against hypoxic-ischemic brain damage via PI3K/Akt/GSK3β pathway. (Pubmed Central) - Jul 22, 2020
Moreover, 0.2, 1, 5 μg/ml oxymatrine improved cell survival, decreased cell apoptosis. The utilization of LY293004 (PI3K signaling pathway inhibitor) also supported that oxymatrine ameliorated neonatal hypoxic-ischemic brain damage and cell injury by controlling NR2B-PI3K/Akt/GSK3β signaling pathway.
- | Journal: LncRNA MALAT1 mediates proliferation of LPS treated-articular chondrocytes by targeting the miR-146a-PI3K/Akt/mTOR axis. (Pubmed Central) - Jul 22, 2020
These results show that MALAT1 can modulate ECM catabolism, inflammation, and especially apoptosis in chondrocytes treated with LPS, which targets PI3K/Akt/mTOR to eventually regulate the progression of OA. Our findings provide a novel regulatory mechanism of MALAT1 in OA.
- | pictilisib (GDC-0941) / Roche
Journal: C-Labeled Pictilisib (GDC-0941) as a Molecular Tracer Targeting Phosphatidylinositol 3-Kinase (PI3K) for Breast Cancer Imaging. (Pubmed Central) - Jul 22, 2020
In conclusion, [C]-pictilisib was first successfully prepared, and it exhibited good potential to identify pictilisib-sensitive tumors noninvasively, which may have a great impact in the treatment of cancers with an overactive PI3K/Akt/mTOR signal pathway. However, the high activity in hepatobiliary system and intestines needs to be addressed.