ArticleLeukemia2020
OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Importance of circulating adipocytokines in multiple myeloma: a systematic review and meta-analysis based on case-control studies.BMC endocrine disorders · 2022Pooled it
- NAPRT Expression and Epigenetic Regulation in Pediatric Rhabdomyosarcoma as a Potential Biomarker for NAMPT Inhibition.Molecular cancer therapeutics · 2026Article
- Physicochemical and Metabolic Optimization of NAMPT Inhibitors Enables Effective Antibody-Drug Conjugates for Liquid and Solid Tumors.ACS bio & med chem Au · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- NAD Metabolism in Acute Myeloid Leukaemia: Biological Rationale and Therapeutic Opportunities.Nutrients · 2026Review
- NAMPT haploinsufficiency is a therapeutic vulnerability to NAMPT inhibition in -7/-7q MDS.Biomarker research · 2026Article
- Inhibition of NAMPT targets DNA damage response to sensitize alkylating chemotherapy in TP53 mutant mantle cell lymphoma.Blood advances · 2026Article
- RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination.Communications biology · 2025Article
- NAMPT haploinsufficiency is a collateral lethal therapeutic vulnerability in high-risk myeloid malignancies withBlood neoplasia · 2025Article
- Targeted Degradation Technologies Utilizing Autophagy.International journal of molecular sciences · 2025Review
- NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.Blood advances · 2025Article
- Single-cell multi-omics analysis identifies SPP1Biomarker research · 2025Article
- Targeting NAD+ Metabolism Vulnerability in FH-Deficient Hereditary Leiomyomatosis and Renal Cell Carcinoma with the Novel NAMPT Inhibitor OT-82.Molecular cancer therapeutics · 2025Article
- Article
- Targeting NAD Metabolism: Rational Design, Synthesis and In Vitro Evaluation of NAMPT/PARP1 Dual-Target Inhibitors as Anti-Breast Cancer Agents.Molecules (Basel, Switzerland) · 2024Article
- Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death.Journal of medicinal chemistry · 2024Review
- A molecular circuit linking the BCR to the NAD biosynthetic enzyme NAMPT is an actionable target in Richter syndrome.Blood advances · 2024Article
- Monosomy 7/del(7q) cause sensitivity to inhibitors of nicotinamide phosphoribosyltransferase in acute myeloid leukemia.Blood advances · 2024Article
- Inhibitors of NADInternational journal of molecular sciences · 2024Review
- The function of nicotinamide phosphoribosyl transferase (NAMPT) and its role in diseases.Frontiers in molecular biosciences · 2024Review
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 2 countries.
Funding
Abstract
Effective treatment of some types of cancer can be achieved by modulating cell lineage-specific rather than tumor-specific targets. We conducted a systematic search for novel agents selectively toxic to cells of hematopoietic origin. Chemical library screenings followed by hit-to-lead optimization identified OT-82, a small molecule with strong efficacy against hematopoietic malignancies including acute myeloblastic and lymphoblastic adult and pediatric leukemias, erythroleukemia, multiple myeloma, and Burkitt's lymphoma in vitro and in mouse xenograft models. OT-82 was also more toxic towards patients-derived leukemic cells versus healthy bone marrow-derived hematopoietic precursors. OT-82 was shown to induce cell death by inhibiting nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage pathway of NAD synthesis. In mice, optimization of OT-82 dosing and dietary niacin further expanded the compound's therapeutic index. In toxicological studies conducted in mice and nonhuman primates, OT-82 showed no cardiac, neurological or retinal toxicities observed with other NAMPT inhibitors and had no effect on mouse aging or longevity. Hematopoietic and lymphoid organs were identified as the primary targets for dose limiting toxicity of OT-82 in both species. These results reveal strong dependence of neoplastic cells of hematopoietic origin on NAMPT and introduce OT-82 as a promising candidate for the treatment of hematological malignancies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.