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DRUG CLASS:

Bcl-xL inhibitor

16h
The PROTAC selectively degrading BCL-XL inhibits the growth of tumors and significantly synergizes with Paclitaxel. (PubMed, Biochem Pharmacol)
However, the clinical development of the small molecule BCL-XL inhibitor ABT-263 has been challenged on account of its on-target and dose-limiting toxicity. Meanwhile, we observed that SIAIS361034 significantly synergized with PTX to inhibit the growth of SCLC xenografts in vivo, without causing exacerbating PTX-induced neutropenia. Taken together, SIAIS361034, shows great potentiality in killing tumors cells, both as a monotherapy and in combination with PTX.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • CRBN (Cereblon)
|
MCL1 expression
|
paclitaxel • navitoclax (ABT 263)
1d
Senolysis by ABT-263 is associated with inherent apoptotic dependence of cancer cells derived from the non-senescent state. (PubMed, Cell Death Differ)
ABT-263 resistant cells however upregulate MCL-1, while sensitive cells exhibit low levels of this anti-apoptotic protein. Overall, our data indicate that the response of senescent cells to ABT-263 is predetermined by the mitochondrial apoptotic priming state of the parental cells, which could serve as a predictive biomarker for response to senolytic therapy.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2)
|
navitoclax (ABT 263)
7d
Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers (clinicaltrials.gov)
P1, N=42, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Feb 2027 | Trial primary completion date: Jun 2026 --> Feb 2027
Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene) • BCL2L1 (BCL2-like 1)
|
Cotellic (cobimetinib) • pelcitoclax (APG-1252)
10d
Enrollment closed • Enrollment change • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2)
|
BCL2 expression
|
Venclexta (venetoclax) • azacitidine • decitabine • navitoclax (ABT 263)
14d
Uncovering cellular senescence as a therapeutic target in NF2-related vestibular schwannoma. (PubMed, Hear Res)
These findings suggest that a one-two punch strategy of pro-senescence therapy induced by chemotherapy treatment followed by senolytic therapy represents a new paradigm for the pharmacological treatment of VS.
Journal
|
IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL1B (Interleukin 1, beta) • MMP1 (Matrix metallopeptidase 1)
|
navitoclax (ABT 263) • bleomycin
19d
HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells. (PubMed, Cell Death Differ)
When analyzing potential therapeutic strategies, we observed a stronger senolytic activity in these melanoma cell lines when specifically targeting BCL-xL using A-1331852, navitoclax or the PROTAC BCL-xL degrader DT2216. Furthermore, we identified that the main apoptotic inhibition was shaped by BCL-xL and BAK binding increase that prevented mitochondrial permeabilization and apoptosis. To our knowledge, this is the first time that the molecular basis for BCL-xL anti-apoptotic adaptation in senescence is described, paving the way for the development of new molecules that either prevent HRK downregulation or displace BCL-xL binding to BAK to be used as senolytics.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2)
|
BAX expression
|
navitoclax (ABT 263) • A-1331852 • DT2216
24d
Novel serous effusion-related risk models and biomarkers for predicting prognosis in T-cell lymphoma patients. (PubMed, Ann Hematol)
Pan-cancer analysis found HIF1A expression was decreased in several tumors, and chemosensitivity analysis revealed that HIF1A was associated with sensitivity of several anti-tumor drugs, such as Sorafenib, Navitoclax, and Venetoclax. Our findings provide evidence for identifying high-risk population and facilitating individualized treatment in TCL patients with SE.
Journal
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • B2M (Beta-2-microglobulin) • COL1A1 (Collagen Type I Alpha 1 Chain) • NFATC1 (Nuclear Factor Of Activated T Cells 1)
|
HIF1A expression
|
Venclexta (venetoclax) • sorafenib • navitoclax (ABT 263)
26d
The novel BCL-2/BCL-XL inhibitor APG-1252-mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer. (PubMed, Acta Pharmacol Sin)
Mechanistically, APG-1252 combined with lapatinib synergistically induced GSDME-mediated pyroptosis in HER2-positive gastric cancer by activating caspase-dependent pathways and blocking the phospho-AKT/GSK-3β/MCL-1 signaling pathway. Our data indicated that the combination of lapatinib and APG-1252 had a synergistic antitumor effect on HER2-positive gastric cancer through the induction of caspase-3/GSDME-mediated apoptosis and pyroptosis.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • GSDME (Gasdermin E)
|
HER-2 positive • HER-2 overexpression
|
lapatinib • pelcitoclax (APG-1252)
1m
Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors (clinicaltrials.gov)
P1, N=29, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Mar 2024
Trial completion • Trial completion date • IO biomarker
|
MCL1 (Myeloid cell leukemia 1) • AFP (Alpha-fetoprotein) • CASP3 (Caspase 3)
|
MCL1 expression
|
sorafenib • navitoclax (ABT 263)
1m
Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma. (PubMed, Nat Commun)
Accordingly, a machine-learning approach identifies a composite molecular and functional signature that best predicts responses of diverse intracranial glioma models to standard-of-care therapies combined with ABBV-155, a clinical drug targeting intrinsic apoptosis. This work demonstrates how complementary functional and molecular data can robustly predict therapy-induced cell death.
Journal
|
TP53 (Tumor protein P53)
|
TP53 wild-type
|
mirzotamab clezutoclax (ABBV-155)
1m
Anti-leukemia efficacy of the dual BCL2/BCL-XL inhibitor AZD0466 in acute lymphoblastic leukemia preclinical models. (PubMed, Blood Adv)
We also evaluated the therapeutic potential of targeting these proteins with AZD0466, a novel drug-dendrimer conjugate of the BCL2/-XL inhibitor AZD4320, and with BCL2 inhibitor venetoclax (ABT-199). Our findings therefore suggest that the novel dual BCL2/-XL inhibitor AZD0466 outperforms single BCL2 inhibition by venetoclax in T-ALL. These findings facilitate the translation of dual BCL2/-XL inhibitors into ALL clinical trials, either alone or in combination with standard- of- care chemotherapy and immune therapies.
Preclinical • Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
|
BCL2 expression
|
Venclexta (venetoclax) • AZD0466 • AZD4320
1m
Exactis-03: Combination of Olaparib and Navitoclax in Women with HGSC and TNBC (clinicaltrials.gov)
P1, N=36, Active, not recruiting, Sunnybrook Health Sciences Centre | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2024 --> Mar 2025
Enrollment closed • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
|
BRCA2 mutation • BRCA1 mutation • PALB2 mutation
|
Lynparza (olaparib) • navitoclax (ABT 263)
1m
Unveiling the role of Pleckstrin-2 in tumor progression and immune modulation: insights from a comprehensive pan-cancer analysis with focus on lung cancer. (PubMed, Mol Biomed)
Compounds like Navitoclax were also identified as potential PLEK2 inhibitors. In conclusion, PLEK2 played a multifaceted role in cancer progression and immune response modulation. Targeting PLEK2 might suppress tumor growth and overcome immunotherapy resistance, offering a promising biomarker and therapeutic target to improve cancer treatment outcomes.
Journal • PD(L)-1 Biomarker • IO biomarker • Pan tumor
|
CD8 (cluster of differentiation 8) • PLEK2 (Pleckstrin 2)
|
navitoclax (ABT 263)
1m
NCI-2013-02103: Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov)
P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date • IO biomarker
|
PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2)
|
BRAF V600E • BRAF mutation • BRAF V600 • PTEN mutation • BRAF V600K
|
THXID® BRAF Kit • cobas® 4800 BRAF V600 Mutation Test
|
Mekinist (trametinib) • Tafinlar (dabrafenib) • navitoclax (ABT 263) • omipalisib (GSK2126458)
2ms
Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax (clinicaltrials.gov)
P1/2, N=35, Active, not recruiting, St. Jude Children's Research Hospital | N=98 --> 35 | Trial completion date: Jul 2029 --> Mar 2025 | Trial primary completion date: Aug 2025 --> Jun 2024
Enrollment change • Trial completion date • Trial primary completion date
|
Venclexta (venetoclax) • dasatinib • cytarabine • cyclophosphamide • etoposide IV • Blincyto (blinatumomab) • vincristine • navitoclax (ABT 263) • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl)
2ms
Establishment of BCL-2 Inhibitors-Resistant B-cell Acute Lymphoblastic Leukemia Cell Lines and Study on Their Resistance Mechanisms (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
Drug-resistant B-ALL cell lines could be successfully established by exposing RS4;11 cell line to the ascending concentration of BCL-2 inhibitors, and the drug resistance mechanism may be related to the overexpression of EP300.
Preclinical • Journal • IO biomarker
|
EP300 (E1A binding protein p300)
|
BCL2 expression • EP300 overexpression
|
Venclexta (venetoclax) • navitoclax (ABT 263)
2ms
Explore the expression of mitochondria-related genes to construct prognostic risk model for ovarian cancer and validate it, so as to provide optimized treatment for ovarian cancer. (PubMed, Front Immunol)
In terms of drug sensitivity, the high-risk group was more sensitive to vinblastine, Acetalax, VX-11e, and PD-0325901, while the low-risk group was more sensitive to Sabutoclax, SB-505124, cisplatin, and erlotinib. The prognostic risk model of ovarian cancer associated to mitochondrial genes built on the basis of public database better evaluated the prognosis of ovarian cancer patients and guided individual treatment.
Journal • Tumor mutational burden • IO biomarker
|
TMB (Tumor Mutational Burden)
|
cisplatin • erlotinib • mirdametinib (PD-0325901) • VTX-11e • vinblastine • sabutoclax (ONT-701)
2ms
Metabolomic Profiling and Network Toxicology: Mechanistic Insights into Effect of Gossypol Acetate Isomers in Uterine Fibroids and Liver Injury. (PubMed, Pharmaceuticals (Basel))
(-)-gossypol acetate and (+)-gossypol acetate play positive roles in the treatment and prevention of uterine fibroids. Gossypol optical isomers cause liver damage through multiple targets and pathways.
Journal • Metabolomic study
|
EGFR (Epidermal growth factor receptor) • BCL2 (B-cell CLL/lymphoma 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MAPK1 (Mitogen-activated protein kinase 1) • CASP3 (Caspase 3) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
|
R-(-)-gossypol (AT 101)
2ms
Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs. (PubMed, Proc Natl Acad Sci U S A)
We showed that inducible ON (iON)-CAR T cells respond to target tumors cells in the presence of venetoclax or the BH3 mimetic navitoclax in a dose-dependent manner, while there is no impact of the drugs on equivalent second generation-CAR T cells. Finally, by fusing a degron sequence to the endodomain of the iON-CAR S-chain we generated an all-in-one ON/OFF-switch CAR, the iONØ-CAR, down-regulated by lenalidomide within 4 to 6 for functionally inactive T cells (no IFNγ production) within 24 h. We propose that our remote-control CAR designs can reduce toxicity in the clinic. Moreover, the periodic rest of iON and iONØ-CAR T cells may alleviate exhaustion and hence augment persistence and long-term tumor control in patients.
Journal
|
IFNG (Interferon, gamma)
|
Venclexta (venetoclax) • lenalidomide • navitoclax (ABT 263)
2ms
Comprehensive functional evaluation of head and neck squamous cell carcinoma with BH3-profiling demonstrates apoptotic competency and therapeutic efficacy of BH3-mimetics. (PubMed, Oral Oncol)
We assessed response to BH3 mimetics including ABT-263 (navitoclax), an inhibitor of Bcl-2/Bcl-xL/Bcl-w, and S63845, an inhibitor of Mcl-1, both as single agents and in combination. We found the combination to be highly synergistic in 2D culture and in 3D organoid models of HHNSCC. Given our findings that co-dependency on Bcl-xL and Mcl-1 is common, and co-inhibition of these molecules is synergistic for growth suppression in HNSCC cells, these results elucidate the therapeutic potential of BCL-xL and MCL-1 inhibition in HNSCC.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2)
|
MCL1 expression
|
navitoclax (ABT 263) • S63845
3ms
BCL-XL-targeting antibody-drug conjugates are active in preclinical models and mitigate on-mechanism toxicity of small-molecule inhibitors. (PubMed, Sci Adv)
While an unprecedented BCL-XL-mediated toxicity was uncovered in monkey kidneys upon repeat dosing of AM1-15, this toxicity was mitigated via further drug-linker modification to afford AM1-AAA (AM1-25). The AAA drug-linker has since been incorporated into mirzotamab clezutoclax, the first selective BCL-XL-targeting agent to enter human clinical trials.
Preclinical • Journal
|
EGFR (Epidermal growth factor receptor) • BCL2L1 (BCL2-like 1)
|
mirzotamab clezutoclax (ABBV-155)
3ms
A Study of LP-118 in Patients with Advanced Tumors (clinicaltrials.gov)
P1, N=96, Active, not recruiting, Guangzhou Lupeng Pharmaceutical Company LTD. | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Jan 2025
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
|
BCL2 (B-cell CLL/lymphoma 2)
|
LP-118
3ms
The Innate Immune System and TRAIL-BCL-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females. (PubMed, Cancer Res)
In both flank and orthotopic models, the BCL-XL inhibitor navitoclax (ABT-263) improved tumor growth control in female mice and required NK cells, macrophages, and the TRAIL signaling pathway. This research suggests that navitoclax and TRAIL pathway agonists could be used as a personalized therapy to improve outcomes in women with lung cancer.
Journal
|
BCL2L1 (BCL2-like 1) • NKG2D (killer cell lectin like receptor K1)
|
navitoclax (ABT 263)
3ms
Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE) (clinicaltrials.gov)
P2, N=52, Active, not recruiting, Unity Biotechnology, Inc. | Recruiting --> Active, not recruiting
Enrollment closed
|
Eylea (aflibercept intravitreal)
3ms
Structural basis of lactate dehydrogenase A-gossypol complex. (PubMed, Biochem Biophys Res Commun)
The binding of gossypol affects LDHA activity by a conformational change in the active-site loop. Our research contributes to the structural insight into LDHA with gossypol and approaches gossypol as a novel therapeutic candidate targeting the metabolic pathways for cancer cells.
Journal
|
LDHA (Lactate dehydrogenase A)
|
R-(-)-gossypol (AT 101)
3ms
Oncogenic Mutant p53 Sensitizes Non-Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress-Dependent Induction of Mitochondrial Apoptosis. (PubMed, Cancer Res Commun)
Validating BTZ's translational potential in Onc-p53 NSCLC cells, BTZ and the BH3-mimetic navitoclax were synergistically cytotoxic in Onc-p53 but not WT p53 cells in vitro, and BTZ effectively limited growth of Onc-p53 NSCLC xenografts when combined with navitoclax and carboplatin (a standard of care chemotherapeutic in NSCLC) in vivo. Our data therefore support further investigation of the therapeutic utility of PIs combined with BH3-mimetics and chemotherapy in Onc-p53 human NSCLC as a novel therapeutic strategy.
Journal
|
TP53 (Tumor protein P53) • CASP3 (Caspase 3) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • ATF3 (Activating Transcription Factor 3)
|
TP53 mutation • TP53 wild-type
|
carboplatin • navitoclax (ABT 263)
3ms
Navitoclax, Venetoclax, and Decitabine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Previously Treated with Venetoclax (clinicaltrials.gov)
P1, N=17, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy
|
Venclexta (venetoclax) • decitabine • navitoclax (ABT 263)
3ms
Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid-Coated Coordination Polymer Nanoparticles. (PubMed, Adv Sci (Weinh))
RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL-6 signal pathways. This work combines MRI imaging with cisplatin-based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.
Journal • MRI
|
IL6 (Interleukin 6)
|
cisplatin • R-(-)-gossypol (AT 101)
3ms
ONC212, alone or in synergistic conjunction with Navitoclax (ABT-263), promotes cancer cell apoptosis via unconventional mitochondrial-independent caspase-3 activation. (PubMed, Cell Commun Signal)
Moreover, inhibition of caspase-9 activity unexpectedly augmented, rather than attenuated, caspase-3 activation and the subsequent cell death. Collectively, our research identifies ONC212 as an atypical mitochondrial-independent, yet Bcl-2/Bcl-xL-inhibitable, caspase-3-mediated apoptotic cell death inducer, highlighting its potential for combination therapies in tumors with defective mitochondrial apoptotic signaling.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • CASP9 (Caspase 9) • ANXA5 (Annexin A5)
|
BCL2 overexpression • BCL2 expression
|
navitoclax (ABT 263) • ONC212
3ms
Gossypol Inhibits Metastasis of Lung Cell Carcinoma by Reversing Epithelial to Mesenchymal Transition and Suppressing Proteases Activity. (PubMed, Environ Toxicol)
Gossypol reduced vimentin, p-FAK, p-Src and p-paxillin. In vivo studies of gossypol were performed using subcutaneous inoculation and tail vein injection of A549 into immunodeficient BALB/c nude mice and severe combined immunodeficient mice.
Journal
|
MMP2 (Matrix metallopeptidase 2) • VIM (Vimentin) • TGFB1 (Transforming Growth Factor Beta 1)
|
R-(-)-gossypol (AT 101)
3ms
IL-17A exacerbates corpus cavernosum fibrosis and neurogenic erectile dysfunction by inducing CSMC senescence via the mTORC2-ACACA pathway. (PubMed, BMC Med)
IL-17A assumes a pivotal role in denervated CCF by activating the mTORC2-ACACA signalling pathway, presenting itself as a potential therapeutic target for effectively overcoming CCF and erection rehabilitation in neurogenic ED.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • IL17A (Interleukin 17A) • ACACA (Acetyl-CoA Carboxylase Alpha)
|
navitoclax (ABT 263)
4ms
HSF1 is a prognostic determinant and therapeutic target in intrahepatic cholangiocarcinoma. (PubMed, J Exp Clin Cancer Res)
The present data underscore the critical pathogenetic, prognostic, and therapeutic role of HSF1 in cholangiocarcinogenesis.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2) • NICD (NOTCH1 intracellular domain) • HSF1 (Heat Shock Transcription Factor 1)
|
navitoclax (ABT 263)
4ms
MERTK Is a Potential Therapeutic Target in Ewing Sarcoma. (PubMed, Cancers (Basel))
Combined treatment with MRX-2843 and BCL-2 inhibitors venetoclax or navitoclax provided enhanced therapeutic activity compared to single agents. These data highlight MERTK as a promising therapeutic target in EWS and provide rationale for the development of MRX-2843 for the treatment of EWS, especially in combination with BCL-2 inhibitors.
Journal
|
MERTK (MER Proto-Oncogene, Tyrosine Kinase)
|
Venclexta (venetoclax) • navitoclax (ABT 263) • MRX2843
4ms
Establishment of a prognostic model for pancreatic cancer based on mitochondrial metabolism related genes. (PubMed, Discov Oncol)
By utilizing a gene signature associated with mitochondrial metabolism, a prognostic model has been established which could be a highly efficient method for predicting the outcomes of PAAD patients.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)
|
Venclexta (venetoclax) • sabutoclax (ONT-701)
4ms
Chromosome instability functions as a potential therapeutic reference by enhancing chemosensitivity to BCL-XL inhibitors in colorectal carcinoma. (PubMed, Acta Pharmacol Sin)
By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC...In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.
Journal
|
BCL2L1 (BCL2-like 1)
|
navitoclax (ABT 263)
4ms
Tryptanthrin targets GSTP1 to induce senescence and increases the susceptibility to apoptosis by senolytics in liver cancer cells. (PubMed, Redox Biol)
Importantly, TRYP exposed the vulnerability of tumor cells and sensitized senescent cells to apoptosis induced by senolytic agent ABT263, a Bcl2 inhibitor. Taken together, our findings reveal that TRYP induces cellular senescence via GSTP1/ROS/DDR/NF-κB/SASP axis, providing a novel potential application in synergizing with senolytic therapy in liver cancer.
Journal
|
GSTP1 (Glutathione S-transferase pi 1)
|
navitoclax (ABT 263)
4ms
Trial completion date • Trial primary completion date • Adverse events • Combination therapy
|
Tagrisso (osimertinib) • docetaxel • ABBV-637
4ms
Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=0, Withdrawn, Medical College of Wisconsin | N=36 --> 0 | Initiation date: May 2024 --> Aug 2024 | Not yet recruiting --> Withdrawn
Enrollment change • Trial initiation date • Trial withdrawal
|
Venclexta (venetoclax) • cytarabine • navitoclax (ABT 263) • mitoxantrone • Neupogen (filgrastim)
5ms
LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclax-resistant chronic lymphocytic leukemia. (PubMed, Haematologica)
Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax responsive and relapsed CLL.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
|
Venclexta (venetoclax) • LP-118
5ms
Biomarkers related to m6A and succinic acid metabolism in papillary thyroid carcinoma. (PubMed, BMC Med Genomics)
Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted.
Journal
|
FGFR2 (Fibroblast growth factor receptor 2) • TNFRSF10B (TNF Receptor Superfamily Member 10b)
|
navitoclax (ABT 263)
5ms
Blockade of CaV3 calcium channels and induction of G0/G1 cell cycle arrest in colon cancer cells by gossypol. (PubMed, Br J Pharmacol)
Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.
Journal
|
CAV3 (Caveolin 3)
|
R-(-)-gossypol (AT 101)
5ms
Combination Navitoclax, Venetoclax and Decitabine for Advanced Myeloid Neoplasms (clinicaltrials.gov)
P1, N=16, Active, not recruiting, Jacqueline Garcia, MD | Recruiting --> Active, not recruiting | N=36 --> 16
Enrollment closed • Enrollment change • Metastases
|
Venclexta (venetoclax) • decitabine • navitoclax (ABT 263)