tbuckley/cabot-search huggingface dataset:
Pharmacological characterization of allosteric modulators: A case for chemokine receptors
Authors: Lisa S. den Hollander, Adriaan P. IJzerman, Laura H. Heitman
Journal: Medicinal Research Reviews (2024)

Abstract Chemokine receptors are relevant targets for a multitude of immunological diseases, but drug attrition for these receptors is remarkably high. While many drug discovery programs have been pursued, most prospective drugs failed in the follow‐up studies due to clinical inefficacy, and hence there is a clear need for alternative approaches. Allosteric modulators of receptor function represent an excellent opportunity for novel drugs, as they modulate receptor activation in a controlled manner and display increased selectivity, and their pharmacological profile can be insurmountable. Here, we discuss allosteric ligands and their pharmacological characterization for modulation of chemokine receptors. Ligands are included if (1) they show clear signs of allosteric modulation in vitro and (2) display evidence of binding in a topologically distinct manner compared to endogenous chemokines. We discuss how allosteric ligands affect binding of orthosteric (endogenous) ligands in terms of affinity as well as binding kinetics in radioligand binding assays. Moreover, their effects on signaling events in functional assays and how their binding site can be elucidated are specified. We substantiate this with examples of published allosteric ligands targeting chemokine receptors and hypothetical graphs of pharmacological behavior. This review should serve as an effective starting point for setting up assays for characterizing allosteric ligands to develop safer and more efficacious drugs for chemokine receptors and, ultimately, other G protein‐coupled receptors.
Neutrophil-derived nanovesicles deliver IL-37 to mitigate renal ischemia-reperfusion injury via endothelial cell targeting
Authors: Wenjie Ma, Di Wu, Chengcheng Long, Jingyu Liu, Luwei Xu, Liuhua Zhou, Quanliang Dou, Yuzheng Ge, Changcheng Zhou, Ruipeng Jia
Journal: Journal of Controlled Release (2024)
Unhealthy Food and Beverage Marketing to Children in the Digital Age: Global Research and Policy Challenges and Priorities
Authors: Emma Boyland, Kathryn Backholer, Monique Potvin Kent, Marie A. Bragg, Fiona Sing, Tilakavati Karupaiah, Bridget Kelly
Journal: Annual Review of Nutrition (2024)

Food and nonalcoholic beverage marketing is implicated in poor diet and obesity in children. The rapid growth and proliferation of digital marketing has resulted in dramatic changes to advertising practices and children's exposure. The constantly evolving and data-driven nature of digital food marketing presents substantial challenges for researchers seeking to quantify the impact on children and for policymakers tasked with designing and implementing restrictive policies. We outline the latest evidence on children's experience of the contemporary digital food marketing ecosystem, conceptual frameworks guiding digital food marketing research, the impact of digital food marketing on dietary outcomes, and the methods used to determine impact, and we consider the key research and policy challenges and priorities for the field. Recent methodological and policy developments represent opportunities to apply novel and innovative solutions to address this complex issue, which could drive meaningful improvements in children's dietary health.
Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study
Authors: Pearl L H Mok, Matthew J Carr, Bruce Guthrie, Daniel R Morales, Aziz Sheikh, Rachel A Elliott, Elizabeth M Camacho, Tjeerd van Staa, Anthony J Avery, Darren M Ashcroft
Journal: BMJ (2024)

Abstract Objective To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia. Design Population based matched cohort study. Setting Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England. Population Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling. Main outcome measures The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding. Results Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%). Conclusions Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.
Lin<sup>−</sup>CD117<sup>+</sup>CD34<sup>+</sup>FcεRI<sup>+</sup> progenitor cells are increased in chronic spontaneous urticaria and predict clinical responsiveness to anti‐<scp>IgE</scp> therapy
Authors: Katie Ridge, Barry Moran, P. Abigail Alvarado‐Vazquez, Jenny Hallgren, Mark A. Little, Alan D. Irvine, Cliona O'Farrelly, Jean Dunne, Conor M. Finlay, Niall Conlon
Journal: Allergy (2024)

Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterized by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage
KRAS G12 mutations as adverse prognostic factors in KMT2A-rearranged acute myeloid leukemia
Authors: Shinju Iyoda, Kenichi Yoshida, Kota Shoji, Nana Ito, Miu Tanaka, Yasuhito Nannya, Genki Yamato, Shinichi Tsujimoto, Norio Shiba, Yasuhide Hayashi, Yusuke Shiozawa, Yuichi Shiraishi, Kenichi Chiba, Ai Okada, Hiroko Tanaka, Satoru Miyano, Yuhki Koga, Hiroaki Goto, Hiroshi Moritake, Kiminori Terui, Etsuro Ito, Nobutaka Kiyokawa, Daisuke Tomizawa, Takashi Taga, Akio Tawa, Junko Takita, Momoko Nishikori, Souichi Adachi, Seishi Ogawa, Hidemasa Matsuo
Journal: Leukemia (2024)
Induction of NK cell reactivity against acute myeloid leukemia by Fc-optimized CD276 (B7-H3) antibody
Authors: Sylwia A. Stefańczyk, Ilona Hagelstein, Martina S. Lutz, Stefanie Müller, Samuel J. Holzmayer, Grace Jarjour, Latifa Zekri, Jonas S. Heitmann, Helmut R. Salih, Melanie Märklin
Journal: Blood Cancer Journal (2024)

Acute myeloid leukemia (AML) remains a therapeutic challenge despite recent therapeutic advances. Although monoclonal antibodies (mAbs) engaging natural killer (NK) cells via antibody-dependent cellular cytotoxicity (ADCC) hold promise in cancer therapy, almost none have received clinical approval for AML, so far. Recently, CD276 (B7-H3) has emerged as a promising target for AML immunotherapy, due to its high expression on leukemic blasts of AML patients. Here, we present the preclinical development of the Fc-optimized CD276 mAb 8H8_SDIE with enhanced CD16 affinity. We demonstrate that 8H8_SDIE specifically binds to CD276 on AML cell lines and primary AML cells and induces pronounced NK cell activation and degranulation as measured by CD69, CD25, and CD107a. Secretion of IFNγ, TNF, granzyme B, granulysin, and perforin, which mediate NK cell effector functions, was induced by 8H8_SDIE. A pronounced target cell-restricted lysis of AML cell lines and primary AML cells was observed in cytotoxicity assays using 8H8_SDIE. Finally, xenograft models with 8H8_SDIE did not cause off-target immune activation and effectively inhibited leukemia growth in vivo. We here present a novel attractive immunotherapeutic compound that potently induces anti-leukemic NK cell reactivity in vitro and in vivo as treatment option for AML.
Identification of senescent, TREM2-expressing microglia in aging and Alzheimer’s disease model mouse brain
Authors: Noa Rachmian, Sedi Medina, Ulysse Cherqui, Hagay Akiva, Daniel Deitch, Dunya Edilbi, Tommaso Croese, Tomer Meir Salame, Javier Maria Peralta Ramos, Liora Cahalon, Valery Krizhanovsky, Michal Schwartz
Journal: Nature Neuroscience (2024)
Genetic modifiers of rare variants in monogenic developmental disorder loci
Authors: Rebecca Kingdom, Robin N. Beaumont, Andrew R. Wood, Michael N. Weedon, Caroline F. Wright
Journal: Nature Genetics (2024)

Abstract Rare damaging variants in a large number of genes are known to cause monogenic developmental disorders (DDs) and have also been shown to cause milder subclinical phenotypes in population cohorts. Here, we show that carrying multiple (2−5) rare damaging variants across 599 dominant DD genes has an additive adverse effect on numerous cognitive and socioeconomic traits in UK Biobank, which can be partially counterbalanced by a higher educational attainment polygenic score (EA-PGS). Phenotypic deviators from expected EA-PGS could be partly explained by the enrichment or depletion of rare DD variants. Among carriers of rare DD variants, those with a DD-related clinical diagnosis had a substantially lower EA-PGS and more severe phenotype than those without a clinical diagnosis. Our results suggest that the overall burden of both rare and common variants can modify the expressivity of a phenotype, which may then influence whether an individual reaches the threshold for clinical disease.
期刊一览
Authors: Sandeep Ravindran
Journal: Ophthalmology (2024)

Stöhr (p. 545) 等人前瞻性地评估了一种新型视网膜投射激光眼镜(laser-eyewear [LEW])技术在角膜病变患者中增强视觉的效果。该技术通过集成摄像头捕获图像,并使用低能量I类激光将其直接投射到视网膜上。对21名受试者的分析表明,与最佳矫正相比,使用 LEW 视远平均视力提高了 0.43 个最小分辨率角对数单位 (logarithm of the minimum angle of resolution [logMAR]),而使用 LEW 的 2 倍放大模式时,视力提高了 0.66 logMAR。与最佳矫正相比,近视力提高了 0.47 logMAR。 21 名受试者中共有 17 名能够通过 LEW 阅读,而 21 名受试者中只有 4 名能够通过最佳矫正视力阅读,且使用 LEW 的受试者与视力相关的生活质量显着提高。作者得出结论,LEW 能够显著提高患者的视力,并改善他们与视力相关的生活质量,表明该设备有可能取代角膜疾病患者的其他低视力辅助设备。
This Issue at a Glance
Authors: Sandeep Ravindran
Journal: Ophthalmology (2024)

Stöhr et al (p. 545) prospectively evaluated the efficacy of a novel retinal projection laser-eyewear (LEW) technology to enhance the vision of individuals with corneal diseases. The technology captures images using an integrated camera and projects them directly onto the retina using a low-energy class I laser. Analysis of 21 subjects revealed a mean visual acuity improvement of 0.43 logarithm of the minimum angle of resolution (logMAR) in distance vision using LEW compared to best correction, with an improvement of 0.66 logMAR when using the LEW's 2× magnification mode.
Size control of ropivacaine nano/micro-particles by soft-coating with peptide nanosheets for long-acting analgesia
Authors: Jing Liu, Weiwei Wu, Fei Peng, Deying Gong, Yi Kang, Yujun Zhang, Congyan Liu, Yuncheng Li, Guoyan Zhao, Feng Qiu, Wensheng Zhang
Journal: Theranostics (2024)

To meet the need of long-acting analgesia in postoperative pain management, slow-releasing formulations of local anesthetics (LAs) have been extensively investigated. However, challenges still remain in obtaining such formulations in a facile and cost-effective way, and a mechanism for controlling the release rate to achieve an optimal duration is still missing.
Abnormal mitochondrial iron metabolism damages alveolar type II epithelial cells involved in bleomycin-induced pulmonary fibrosis
Authors: Min Shao, Haipeng Cheng, Xiaohong Li, Yujia Qiu, Yunna Zhang, Yanfen Chang, Jiafeng Fu, Mengxia Shen, Xinxin Xu, Dandan Feng, Yang Han, ShaoJie Yue, Yan Zhou, Ziqiang Luo
Journal: Theranostics (2024)

Pulmonary fibrosis is a chronic progressive lung disease with limited therapeutic options. We previously revealed that there is iron deposition in alveolar epithelial type II cell (AECII) in pulmonary fibrosis, which can be prevented by the iron chelator deferoxamine. However, iron in the cytoplasm and the mitochondria has two relatively independent roles and regulatory systems. In this study, we aimed to investigate the role of mitochondrial iron deposition in AECII injury and pulmonary fibrosis, and to find potential therapeutic strategies.
AXL-specific single domain antibodies show diagnostic potential and anti-tumor activity in Acute Myeloid Leukemia
Authors: Niels Vandewalle, Hatice Satilmis, Emma Verheye, Rong Fan, Yanmeng Wang, Timo W.M. De Groof, Jessica Bridoux, Tessa Kerre, Nathan De Beule, Ann De Becker, Elke De Bruyne, Eline Menu, Karin Vanderkerken, Karine Breckpot, Nick Devoogdt, Kim De Veirman
Journal: Theranostics (2024)

AXL expression has been identified as a prognostic factor in acute myeloid leukemia (AML) and is detectable in approximately 50% of AML patients. In this study, we developed AXL-specific single domain antibodies (sdAbs), cross-reactive for both mouse and human AXL protein, to non-invasively image and treat AXL-expressing cancer cells.
NAD<sup>+</sup> precursors promote the restoration of spermatogenesis in busulfan-treated mice through inhibiting Sirt2-regulated ferroptosis
Authors: Yan-Qin Feng, Xuan Liu, Ning Zuo, Mu-Bin Yu, Wen-Meng Bian, Bao-Quan Han, Zhong-Yi Sun, Massimo De Felici, Wei Shen, Lan Li
Journal: Theranostics (2024)

In recent years, nicotinamide adenine dinucleotide (NAD
Albumin-seeking dyes with adjustable assemblies <i>in situ</i> enable programmable imaging windows and targeting tumor imaging
Authors: Yijing Du, Jiajun Xu, Tianyang Han, Zijian Jiang, Yuewei Zhang, Jia Li, Xiaoyuan Chen, Shoujun Zhu
Journal: Theranostics (2024)

Cyanine dyes are widely used organic probes for
Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis
Authors: Rui Wang, Tongyao Liu, Xinhong Li, Enhao Lu, Yiting Chen, Kuankuan Luo, Tao Wang, Xueli Huang, Zhiwen Zhang, Shilin Du, Xianyi Sha
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.
Library size confounds biology in spatial transcriptomics data
Authors: Dharmesh D. Bhuva, Chin Wee Tan, Agus Salim, Claire Marceaux, Marie A. Pickering, Jinjin Chen, Malvika Kharbanda, Xinyi Jin, Ning Liu, Kristen Feher, Givanna Putri, Wayne D. Tilley, Theresa E. Hickey, Marie-Liesse Asselin-Labat, Belinda Phipson, Melissa J. Davis
Journal: Genome biology (2024)

Abstract Spatial molecular data has transformed the study of disease microenvironments, though, larger datasets pose an analytics challenge prompting the direct adoption of single-cell RNA-sequencing tools including normalization methods. Here, we demonstrate that library size is associated with tissue structure and that normalizing these effects out using commonly applied scRNA-seq normalization methods will negatively affect spatial domain identification. Spatial data should not be specifically corrected for library size prior to analysis, and algorithms designed for scRNA-seq data should be adopted with caution.
Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?
Authors: Lioba Huelsboemer, Leonard Knoedler, Alejandro Kochen, Catherine T. Yu, Helia Hosseini, Katharina S. Hollmann, Ashley E. Choi, Viola A. Stögner, Samuel Knoedler, Henry C. Hsia, Bohdan Pomahac, Martin Kauke-Navarro
Journal: Military Medical Research (2024)

Abstract Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.
An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial
Authors: Amit Saraf, Rohan Gurjar, Swarnendu Kaviraj, Aishwarya Kulkarni, Durgesh Kumar, Ruta Kulkarni, Rashmi Virkar, Jayashri Krishnan, Anjali Yadav, Ekta Baranwal, Ajay Singh, Arjun Raghuwanshi, Praveen Agarwal, Laxman Savergave, Sanjay Singh, Himanshu Pophale, Prakash Shende, Ravindra Baban Shinde, Vikram Vikhe, Abhishek Karmalkar, Bhaskar Deshmukh, Krishna Giri, Shrikant Deshpande, Ajay Bulle, Md. Sabah Siddiqui, Swapnav Borthakur, V. Reddy Tummuru, A. Venkateshwar Rao, Dhaiwat Shukla, Manish Kumar Jain, Pankaj Bhardwaj, Pravin Dinkar Supe, Manoja Kumar Das, Manoj Lahoti, Vijaykumar Barge
Journal: Nature Medicine (2024)

Abstract Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific (BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM ( P &lt; 0.0001) and GEMCOVAC-19 ( P &lt; 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM ( P &lt; 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm ( P &lt; 0.0001), but not in the ChAdOx1 nCoV-19 arm ( P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio &gt;1 and difference in seroconversion &gt;0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM ( P &lt; 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475 .
PERCEPTION predicts patient response and resistance to treatment using single-cell transcriptomics of their tumors
Authors: Sanju Sinha, Rahulsimham Vegesna, Sumit Mukherjee, Ashwin V. Kammula, Saugato Rahman Dhruba, Wei Wu, D. Lucas Kerr, Nishanth Ulhas Nair, Matthew G. Jones, Nir Yosef, Oleg V. Stroganov, Ivan Grishagin, Kenneth D. Aldape, Collin M. Blakely, Peng Jiang, Craig J. Thomas, Cyril H. Benes, Trever G. Bivona, Alejandro A. Schäffer, Eytan Ruppin
Journal: Nature Cancer (2024)
The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia
Authors: Hannah Lawson, James P. Holt-Martyn, Vilma Dembitz, Yuka Kabayama, Lydia M. Wang, Aarushi Bellani, Samanpreet Atwal, Nadia Saffoon, Jozef Durko, Louie N. van de Lagemaat, Azzura L. De Pace, Anthony Tumber, Thomas Corner, Eidarus Salah, Christine Arndt, Lennart Brewitz, Matthew Bowen, Louis Dubusse, Derek George, Lewis Allen, Amelie V. Guitart, Tsz Kan Fung, Chi Wai Eric So, Juerg Schwaller, Paolo Gallipoli, Donal O’Carroll, Christopher J. Schofield, Kamil R. Kranc
Journal: Nature Cancer (2024)

Abstract Acute myeloid leukemia (AML) is a largely incurable disease, for which new treatments are urgently needed. While leukemogenesis occurs in the hypoxic bone marrow, the therapeutic tractability of the hypoxia-inducible factor (HIF) system remains undefined. Given that inactivation of HIF-1α/HIF-2α promotes AML, a possible clinical strategy is to target the HIF-prolyl hydroxylases (PHDs), which promote HIF-1α/HIF-2α degradation. Here, we reveal that genetic inactivation of Phd1 / Phd2 hinders AML initiation and progression, without impacting normal hematopoiesis. We investigated clinically used PHD inhibitors and a new selective PHD inhibitor (IOX5), to stabilize HIF-α in AML cells. PHD inhibition compromises AML in a HIF-1α-dependent manner to disable pro-leukemogenic pathways, re-program metabolism and induce apoptosis, in part via upregulation of BNIP3. Notably, concurrent inhibition of BCL-2 by venetoclax potentiates the anti-leukemic effect of PHD inhibition. Thus, PHD inhibition, with consequent HIF-1α stabilization, is a promising nontoxic strategy for AML, including in combination with venetoclax.