ABT-737
ABT-737, injectable BH3 mimetic inhibitor of BCL-2, BCL-xL and BCL-w
Written by Aaron CuhaReviewed Sep 2026
Also known as: ABT737
The laboratory predecessor of navitoclax, used as a senolytic tool compound in mice. No one has ever been given ABT-737 in a published clinical study; it is not orally bioavailable, which is why the orally available analogue was developed and taken into people instead.
Overview
ABT-737 is a BH3 mimetic that binds BCL-2, BCL-xL and BCL-w and triggers apoptosis in cells that depend on them. It is the parent compound of navitoclax, which the ovarian cancer investigators describe plainly as the orally available ABT-737 analogue. ABT-737 itself has poor oral bioavailability and has stayed a research tool.
Its place in the senescence literature is as the reagent used to show that killing BCL-2-dependent senescent cells changes disease course in mice. In non-obese diabetic mice, a subset of beta cells acquired a senescence-associated secretory phenotype and upregulated BCL-2, and treating the animals with BCL-2 inhibitors eliminated those cells, halted immune-mediated beta cell destruction and prevented diabetes. In the 5xFAD amyloidosis mouse, ABT-737 reduced a population of senescent, TREM2-expressing microglia without depleting disease-associated microglia. In KRAS-driven mouse lung cancer, senolytic ablation of senescent macrophages reduced tumour burden and increased survival.
There is no human evidence for ABT-737. No published clinical trial has administered it, and none is registered. What human data exist in this drug class come from navitoclax, whose phase 1 programme established that high-affinity BCL-xL inhibition causes dose-limiting thrombocytopenia in people. No senolytic has improved a clinical outcome in a randomised trial in humans, and ABT-737 has not been given to a human at all.
Mechanism of action
Established in cells and in mice: ABT-737 occupies the BH3 binding groove of BCL-2, BCL-xL and BCL-w, releasing BAX and BAK and committing the cell to apoptosis. Senescent cells in mouse tissues upregulate these proteins to survive, which is the basis of the selectivity seen in animal experiments. Nothing about this mechanism has been characterised in a person given ABT-737, because no person has been given it in a published study.
Human evidence
None. No published study has given ABT-737 to a human, and no trial of it is registered. The human record for this drug class belongs to navitoclax, its orally available analogue.
What this does not tell you: Because ABT-737 has never been dosed in a person, nothing is known about its human pharmacokinetics, tolerated dose, or whether the senolytic selectivity seen in mouse tissues would appear in human tissue. The navitoclax experience suggests the limiting factor would be the same one: platelets depend on BCL-xL.
Reading the research record
ABT-737 is best understood as a laboratory reagent that generated important mouse biology rather than as a drug candidate. Its poor oral bioavailability is exactly why Abbott developed navitoclax, and navitoclax is where the human data and the human toxicity live. Papers that describe ABT-737 as a senolytic are describing what it does in mouse tissue and cultured cells.
The practical consequence is that anyone reading a headline about senescent cells being cleared in Alzheimer's or diabetes models should check which compound was used and in which species. In all three of the studies above, it was a mouse.
The evidence, charted
Fig. 1 · evidence composition
2of 5 citations (40%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 5 distinct years, 2010 to 2024, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Not approved
CA
Not approved
Approved in 1 of 4, prescription route in 0, not approved in 3. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Animal2019
Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes
Mouse (non-obese diabetic model), with descriptive human pancreas observations. Senescent beta cells upregulated BCL-2; treating the mice with BCL-2 inhibitors selectively eliminated those cells, halted immune-mediated beta cell destruction and prevented diabetes. The disease prevention is a mouse result.
Cell Metabolism - Animal2024
Identification of senescent, TREM2-expressing microglia in aging and Alzheimer's disease model mouse brain
Mouse. In the 5xFAD amyloidosis model, treatment with the senolytic BCL-2 family inhibitor ABT-737 reduced senescent microglia without depleting the disease-associated microglia population.
Nature Neuroscience - Animal2023
Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer
Mouse. Genetic or senolytic ablation of senescent cells, or macrophage depletion, reduced tumour burden and increased survival in KRAS-driven lung cancer models. Macrophages with senescent features were also found in human pre-malignant lung lesions, an observation rather than an intervention.
Cancer Cell - Human2010
Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study
The only human data in this drug class, and it is about the oral analogue, not ABT-737. 55 adults with lymphoid malignancy; grade 3 or 4 thrombocytopenia in 29, attributed by the authors to high-affinity BCL-xL inhibition. Funded by Abbott Laboratories, Genentech and the National Cancer Institute.
The Lancet Oncology - Human2022
A phase II study of Navitoclax (ABT-263) as single agent in women heavily pretreated for recurrent epithelial ovarian cancer
The source that states the relationship directly: navitoclax is described as the orally available ABT-737 analogue. 46 women, median progression-free survival 1.64 months, grade 3 or 4 thrombocytopenia in 12 of 46.
Gynecologic Oncology
Frequently asked questions
Has ABT-737 ever been given to a person?
Not in any published clinical study, and no trial of it is registered. Its oral analogue navitoclax has been given to people, in cancer trials only.
What is the difference between ABT-737 and navitoclax?
Navitoclax is the orally bioavailable analogue of ABT-737, developed because ABT-737 is not absorbed well enough by mouth to be a practical drug. They inhibit the same proteins, BCL-2, BCL-xL and BCL-w.
What has ABT-737 shown in animals?
It prevented diabetes in non-obese diabetic mice by eliminating senescent beta cells, reduced senescent TREM2-expressing microglia in a mouse amyloid model, and in KRAS-driven mouse lung cancer senolytic ablation reduced tumour burden and extended survival. All mouse.