triciribine phosphate (PTX-200) / VioQuest, Cahaba, Prescient Therap - LARVOL DELTA

Dual inhibition of AKT and autophagy sensitizes triple negative breast cancer cells to carboplatin. (PubMed, Transl Oncol) - "Current clinical treatments, primarily chemotherapy regimens based on paclitaxel and anthracycline, are associated with high recurrence rates and low overall survival rates...Further investigation demonstrated that CBP activates the AKT pathway in MDA-MB-231 cells, while its combination with LY294002 or Triciribine (inhibitors of the PI3K/AKT pathway), suppresses cell proliferation...In other words, low doses of EM-2 combined with CBP produced the same anti-tumor effects as high-dose CBP alone. These findings provide a novel strategy for the treatment of CBP using dual AKT and autophagy inhibitors, highlighting potential clinical applications."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Synergistic anti-proliferative effects of JIN-001, a novel HSP90 selective inhibitor, in combination with platinum-based drugs in ovarian cancer cell lines (AACR 2025) - "Here, We investigated the anti-proliferative effects of JIN-001, a selective HSP90i, combined with platinum-based drugs in OC cell lines.Material and We examined the co-treatment effects of JIN-001 and paclitaxel (PTX) or cisplatin (Cis, platinum-based) on viability in OC cell lines (OV90, TOV21G, and OVCAR3) and drug-resistance sublines (OV90/PTX200, TOV21G/PTX100, and OVCAR3-CisR). The combination of JIN-001 with PTX or Cis enhanced anti-proliferative effects and reduced IC50 in OC cell lines and drug-resistant sublines compared to monotherapy. This suggests JIN-001's potential as a combination therapy with platinum-based drugs in OC patients. Further studies are needed to examine whether the combination therapy of JIN-001 and the conventional drugs decelerates the tumor's ability to adapt and develop drug resistance."

Combination therapy • Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CDC37 • HSP90AA1 • PRDX2

Stage-dependent proteomic alterations in aqueous humor of diabetic retinopathy patients based on data-independent acquisition and parallel reaction monitoring. (PubMed, J Transl Med) - "This study established a comprehensive AH proteomic signature of DR progression, offering insights into the pathogenesis of DR and highlighting potential biomarkers and novel therapeutic targets."

Biomarker • Journal • Cataract • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders • Type 2 Diabetes Mellitus • RBP4 • SPP1

Akt inhibition is effective against PTEN-deleted, chemoirradiation-resistant glioblastoma stem cells. (PubMed, Growth Factors) - "Akt X (20 µM) proved more effective at inducing in vitro GSC cytotoxicity (range: 22-73%) over 48 hours than triciribine (20 µM) (0-27%), although both agents inhibited Akt phosphorylation as detected by western blot analysis. A statistically significant correlation between PTEN loss (western blot) and the extent of Akt X-induced cytotoxicity was found (p = 0.03). Akt inhibition reduces in vitro proliferation of treatment-resistant GSC lines, especially in PTEN-deficient lines, warranting further translational investigation in glioblastoma."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • EGFR • PTEN

Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling. (PubMed, Int J Mol Med) - "Of note, the silencing of Sirt1 and administration of triciribine (an AKT inhibitor) both eliminated the protective effect of Cur. Thus, Cur maintained cardiomyocyte function by inhibiting autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling."

Journal • Cardiovascular • Myocardial Ischemia • Reperfusion Injury

Identification of small molecule agonists of fetal hemoglobin expression for the treatment of sickle cell disease. (PubMed, PLoS One) - "These include several known HbF inducers, such as pomalidomide, lenalidomide, decitabine, idoxuridine, and azacytidine, which validate the translational nature of this screening platform. We identified avadomide, autophinib, triciribine, and R574 as novel HbF inducers from these screens...Further, we demonstrated that pomalidomide and avadomide, but not idoxuridine, induced HbF expression through downregulation of several transcriptional repressors such as BCL11A, ZBTB7A, and IKZF1. These studies demonstrate a robust phenotypic screening workflow that can be applied to large-scale small molecule profiling campaigns for the discovery of targets and pathways, as well as novel therapeutics for sickle cell disease and other β-hemoglobinopathies."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HBG1 • IKZF1 • ZBTB7A

Increased in vitro production of bovine embryos resulting from oocyte maturation in the presence of triciribine, a specific inhibitor of AKT. (PubMed, Theriogenology) - "It is concluded that the Akt pathway participates in the nuclear and cytoplasmic events of in vitro maturation of bovine oocytes, but through mechanisms that do not interfere with germinal vesicle breakdown. Modulation of Akt activity in bovine COCs during IVM with 1 μM of triciribine increases the in vitro production of bovine embryos."

Journal • Preclinical

Scaffold Hopping Method for Design and Development of Potential Allosteric AKT Inhibitors. (PubMed, Mol Biotechnol) - "Triciribine, a traditional allosteric AKT inhibitor was used as the template, and the FDA-approved kinase inhibitors for cancer treatment were considered as the cores...Scaffold hopping is a tremendous tool for designing novel anti-cancer agents by improving already known and potential drug compounds. The designed compounds are worth to be examined by experimental investigation in vitro and in vivo."

Journal • Oncology

Synergistic effect of JIN-001, a novel HPS90 selective inhibitor, with platinum or paclitaxel on multi-resistant ovarian cancer (EORTC-NCI-AACR 2024) - "To generate a drug resistant subline, cells were exposed to IC50 concentration of paclitaxel (PTX) or cisplatin (Cis) and gradually exposed to higher concentrations. The drug resistance sub-cell lines were used including PTX200, PTX100, or CisR, respectively...This suggests the benefit of shutting down tumor adaptation while eradicating the tumor rather than focusing on tumor eradication in the short term. Further studies are needed to demonstrate the ability of JIN-001 to retard the tumor's ability to adapt and develop treatment resistance."

Oncology • Ovarian Cancer • Solid Tumor • CDC37 • PRDX2

Signaling effect, combinations, and clinical applications of triciribine. (PubMed, J Chemother) - "Triciribine (TCN) is a tricyclic nucleoside. Although a single dose of TCN demonstrated limited activity in solid tumors at the clinical level, combinations of TCN with various agents, such as specific inhibitors, tyrosine kinase inhibitor dasatinib, ErbB inhibitor tipifarnib, IGF1-R inhibitor NVP-AEW541, mTORC1 inhibitor RAD-001, TNF-related apoptosis-inducing ligand, PPARγ agonist, 1,25(OH)2D3, gemcitabine, and paclitaxel, have been reported to be efficient against various malignancies such as pancreatic, breast, prostate cancer, insulinoma, gut neuroendocrine tumor, and hepatocellular carcinoma at the preclinical level. Other than malignancies, through Akt inhibition activity, TCN has also been demonstrated potential for treating lung injuries, including those encountered in COVID-19 infections."

Journal • Review • Breast Cancer • Endocrine Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Infectious Disease • Neuroendocrine Tumor • Novel Coronavirus Disease • Oncology • Pancreatic Cancer • Prostate Cancer • Respiratory Diseases • Solid Tumor • IGF1

Crosstalk among WEE1 Kinase, AKT, and GSK3 in Nav1.2 Channelosome Regulation. (PubMed, Int J Mol Sci) - "Concerted regulation by WEE1 inhibitor II, triciribine, and GSK3 inhibitor XIII was also observed in long-term inactivation and use dependency of Nav1.2 currents. Overall, these findings suggest a complex role for WEE1 kinase-in concert with the AKT/GSK3 pathway-in regulating the Nav1.2 channelosome."

Journal • NAV1

Emodin alleviates intestinal ischemia/reperfusion-induced lung injury by upregulating HO-1 expression via PI3K/AkT pathway. (PubMed, Surgery) - "In conclusion, our data suggest that emodin treatment protects against intestinal ischemia/reperfusion-induced lung injury by enhancing heme oxygenase-1 expression via activation of the PI3K/protein kinase pathway. Emodin may act as a potential therapeutic agent for the prevention and treatment of lung injury induced by intestinal ischemia/reperfusion."

Journal • Cardiovascular • Inflammation • Reperfusion Injury • Respiratory Diseases • HMOX1

Identification of triciribine as a novel myeloid cell differentiation inducer. (PubMed, PLoS One) - "Using a nitroblue tetrazolium dye reduction assay and real-time quantitative PCR using NB4 APL cells, we revealed that, PD169316, SB203580, SB202190 (p38 MAPK inhibitor), and triciribine (TCN) (Akt inhibitor) potently increased the expression of CD11b. Real-time PCR analysis demonstrated that components of these pathways including IL1β, CD3D, IL5RA, ITGA6, CD44, ITGA2B, CD37, CD9, CSF2RA, and IL3RA, were upregulated by TCN-induced differentiation. Collectively, we identified TCN as a novel myeloid cell differentiation inducer, and trials of TCN for APL and non-APL leukemia are worthy of exploration in the future."

Journal • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD123 • CD3D • CD9 • IL1B • IL3RA • ITGA2B • ITGA6 • ITGAM • ITGAX

Targeting CXCR4 impaired T regulatory function through PTEN in renal cancer patients. (PubMed, Br J Cancer) - "R54 impairs Tregs function in primary RCC patients targeting PTEN/PI3K/AKT pathway, reducing TSDR demethylation and FOXP3 and DNMT1 expression. Thus, CXCR4 targeting is a strategy to inhibit Tregs activity in the RCC tumour microenvironment."

IO biomarker • Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD40LG • CTLA4 • CXCL12 • DNMT1 • FOXP3 • IFNG • IL10 • IL2 • IL2RA • NRP1 • PD-1 • PTEN • TGFB1

Crtc1 deficiency protects against sepsis-associated acute lung injury through activating akt signaling pathway. (PubMed, J Inflamm (Lond)) - "Our study demonstrates that CRTC1 contribute to the pathological processes of inflammation and apoptosis in sepsis-induced ALI, and provides mechanistic insights into the molecular function of CRTC1 in the lung. Targeting CRTC1 would be a promising strategy to treat sepsis-induced ALI in clinic."

Journal • Acute Lung Injury • Infectious Disease • Inflammation • Respiratory Diseases • Septic Shock • CRTC1 • CXCL1 • IL1B • IL6 • TNFA

Targeting CXCR4 impaired T regulatory function through PTEN in renal cancer patients (AACR 2024) - "PTEN-pAKT signaling was evaluated in the presence of R54 and/or triciribine (TCB), Akt inhibitor... The CXCR4 antagonist R54 affects Tregs function in primary RCC patients through regulation of PTEN/PI3K/AKT pathway, reduction in TSDR demethylation and Foxp3 and DNMT1 expression. CXCR4 targeting is thus a strategy to inhibit Tregs activity contributing to the CXCR4 function in RCC tumor microenvironment."

Clinical • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CXCL12 • DNMT1 • FOXP3 • IL2 • IL2RA • NRP1 • PTEN • TGFB1

A Study of PTX-200 (Triciribine) Plus Cytarabine in Refractory or Relapsed Acute Leukemia (clinicaltrials.gov) - P1/2 | N=33 | Completed | Sponsor: Prescient Therapeutics, Ltd. | Recruiting ➔ Completed | Trial completion date: Dec 2021 ➔ Mar 2024 | Trial primary completion date: Dec 2021 ➔ Oct 2023

Trial completion • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

The Role of ZNF275/AKT Pathway in Carcinogenesis and Cisplatin Chemosensitivity of Cervical Cancer Using Patient-Derived Xenograft Models. (PubMed, Cancers (Basel)) - "Collectively, the current findings demonstrated that ZNF275 serves as a sufficiently predictive indicator of the therapeutic effectiveness of the combined treatment of triciribine and cisplatin on cervical cancer. Combining triciribine with cisplatin greatly broadens the therapeutic options for cervical cancer expressing high ZNF275, but further research is needed to confirm these results."

IO biomarker • Journal • Preclinical • Cervical Cancer • Oncology • Solid Tumor • BCL2

Encouraging outcomes from Prescient Therapeutics’ (ASX: PTX) clinical-stage assets light up last quarter (Kalkine Media) - "PTX to present PTX-100 Phase 1b trial data...The trial is nearing completion, and the company expects to share the results in December 2023...In 1Q 2024, the company intends to meet the US FDA with focus on the design of Phase 2 trial, including the potential to use the trial as a registrational study and the endpoints...To assist the Phase 2 trial, the company has commenced the production of additional PTX-100 drug product...The PTX-200 study in acute myeloid leukemia (AML) is nearing completion. To finalise the data package, PTX seeks to enrol a final patient and assess any avenues for PTX-100 development....The latest results indicated that pre-treatment with CellPryme has the capability to enhance the in vivo function of CAR-T cells expanded in IL2/7. The results are superior to existing cytokines."

FDA event • P1 data • Preclinical • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

A multi-arm, parallel, preclinical study investigating the potential benefits of acetazolamide, candesartan, and triciribine in combination with fluconazole for the treatment of cryptococcal meningoencephalitis. (PubMed, Eur J Pharmacol) - "Interestingly, although C. neoformans did not cause brain or lung edema in mice, it induced lung and brain injuries, which were significantly reversed by AZA, CAN, or TCBN. Our study provides novel insights into the direct effects of C. neoformans on BECs in vitro, and the potential benefits of using AZA, CAN, or TCBN in the management of CM patients."

Combination therapy • Journal • Preclinical • CNS Disorders • Infectious Disease • Respiratory Diseases • Vascular Neurology • CDH5 • CLDN5

Non-canonical Ca- Akt signaling pathway mediates the antiproteolytic effects induced by oxytocin receptor stimulation in skeletal muscle. (PubMed, Biochem Pharmacol) - "Thus, rat oxidative skeletal muscles were isolated and incubated with OXT or WAY-267,464, a non-peptide selective OXT receptor (OXTR) agonist, in the presence or absence of atosiban (ATB), an OXTR antagonist, and overall proteolysis was evaluated. Most of these effects were blocked by the inhibition of inositol triphosphate receptors (IP3R), which mediate Ca release from the sarcoplasmic reticulum to the cytoplasm, and triciribine, an Akt inhibitor. Taken together, these findings indicate that the stimulation of OXTR directly induces skeletal muscle protein-sparing effects through a Gαq/IP3R/Ca-dependent pathway and crosstalk with Akt/FoxO1 signaling, which consequently decreases the expression of genes related to atrophy, such as LC3, as well as muscle proteolysis."

Journal • Infectious Disease • Respiratory Diseases • Targeted Protein Degradation

Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (ESMO 2023) - P2 | "All pts received R 10 mg/kg, CBDCA AUC5 and PTX 200 mg/m2 d1q21 for 6 cycles, followed by R 10 mg/kg maintenance until disease progression or intolerable toxicity. Conclusions In previously untreated advanced TC, the addition of R to CBDCA and PTX showed highest activity compared to historical controls, with manageable safety profile. Despite the small number of pts, given the rarity of the disease, these results support the use of this combination as first line treatment in TC."

Clinical • Late-breaking abstract • Metastases • P2 data • Oncology • Solid Tumor • Thymic Carcinoma • Thymus Cancer

Pharmacological inhibiting STAT5 for the treatment of FLT3-ITD-positive acute myeloid leukemia with triciribine phosphate monohydrate. (PubMed, MedComm (2020)) - No abstract available

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • STAT5 • STAT5AWqe

Acquired AKT-inhibitor Resistance Is Mediated by ATP-binding Cassette Transporters in Endometrial Carcinoma. (PubMed, Anticancer Res) - "In this study, we established a triciribine-resistant cell line from HEC-151 cells. Our data suggest that the mechanism of drug resistance in endometrial cancer cells is attributed to the increased expression of ABC transporters."

Journal • Endometrial Cancer • Oncology • Solid Tumor • ABCB1 • ABCC1

Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative retinopathy. (PubMed, Biomed Pharmacother) - "We conclude that TCBN protects against pathological neovascularization, restores blood-retinal barrier homeostasis, and reduces retinal inflammation without adversely affecting the retinal structure and neuronal function in a mouse model of OIR. Our data suggest that TCBN may provide a novel therapeutic option for proliferative retinopathy."

Journal • Preclinical • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders • CDKN1A • CLDN5 • IL6 • TNFA