Navitoclax; RG 7423; RG 7433; CAS 923564-51-6 · Evidence-based safety and harm-reduction overview.
| Also known as | Navitoclax; RG 7423; RG 7433; CAS 923564-51-6 |
| Category | Research Chemical |
| CAS Number | 923564-51-6 |
| Originator | Abbott Laboratories (now AbbVie); collaboration with Genentech/Roche |
| Mechanism class | BH3-mimetic; pan-BCL-2 family inhibitor (BCL-2, BCL-xL, BCL-w, BCL-B) |
| Binding affinity | Ki <1 nM for BCL-2, BCL-xL, and BCL-w in biochemical assays |
| Highest phase reached | Phase 2 (oncology); no approved indication; senolytic use preclinical only |
| Primary dose-limiting toxicity (humans) | Thrombocytopenia: ~70% platelet reduction at 250 mg; reversible on interruption |
| US legal status | Not FDA-approved. Investigational drug only. Multiple Phase 1-2 clinical trials completed or terminated; no approval pathway has advanced beyond Phase 2. Not lawfully sold for human consumption in the United States. AbbVie holds development rights. Research use only. |
ABT-263 (navitoclax) is an orally bioavailable BH3-mimetic small molecule developed by Abbott Laboratories (now AbbVie) in collaboration with Genentech. It inhibits the anti-apoptotic BCL-2 family proteins BCL-2, BCL-xL, BCL-w, and BCL-B with sub-nanomolar affinity (Ki <1 nM), restoring the ability of cancer cells and senescent cells to undergo programmed cell death. It is the orally bioavailable successor to ABT-737, which required intravenous administration. Research interest has expanded beyond oncology to include senolytic (senescent-cell-clearing) applications in aging and age-related diseases, though all human data remain in early clinical phases and no therapeutic indication has been approved.
ABT-263 competitively binds the hydrophobic BH3-binding groove of BCL-2, BCL-xL, BCL-w, and BCL-B, displacing pro-apoptotic proteins (Bim, Bad, Bak) that are sequestered by these survival factors. Displacement allows pro-apoptotic signaling to proceed, culminating in mitochondrial outer membrane permeabilization, cytochrome c release, and caspase-dependent apoptosis. Senolytic activity is attributed to the same mechanism: senescent cells upregulate BCL-2 family survival proteins as part of their apoptosis-resistance program, and ABT-263 overcomes this resistance. BCL-xL inhibition independently mediates dose-dependent platelet reduction, which is the primary dose-limiting toxicity observed in human trials.
ABT-263 emerged from structure-activity optimization of ABT-737, a BCL-2/BCL-xL inhibitor with potent in vitro and in vivo activity but poor oral bioavailability. Abbott Laboratories published navitoclax in 2008 and advanced it into Phase 1 trials in chronic lymphocytic leukemia (CLL) and small cell lung cancer (SCLC). Multiple combination trials with erlotinib, docetaxel, carboplatin/paclitaxel, and rituximab followed. Phase 2 monotherapy data in SCLC (2012) showed modest activity but dose-limiting thrombocytopenia that prevented dose escalation to potentially therapeutic levels. Development in oncology stalled at Phase 2 as the BCL-2-selective venetoclax (ABT-199) - which spares platelets by avoiding BCL-xL - advanced to approval. Interest in ABT-263 as a senolytic emerged after 2015 preclinical findings; translational work in aged animal models continued through 2024-2026, exploring topical formulations and targeted delivery strategies to circumvent systemic thrombocytopenia.
Human clinical data are limited to Phase 1-2 trials and should not be extrapolated to general use. In Phase 1 CLL and SCLC trials, ABT-263 was tolerable at continuous doses up to 250 mg/day (21-day on/21-day off schedule), though platelet reduction was concentration-dependent and ranged from approximately 12% at 10 mg to approximately 70% at 250 mg. Platelet nadir was reversible upon drug interruption. A Phase 2 monotherapy study in SCLC demonstrated some antitumor activity but insufficient single-agent efficacy to support registration. Combination trials with standard chemotherapy agents documented additive toxicity profiles. Preclinical data in animal models are substantially more extensive: senolytic clearance of p16-positive senescent cells has been demonstrated in aged mouse skin, bone, vascular endothelium, and brain tissue, with associated improvements in wound healing, bone density, vascular function, and cognition. A 2026 study reported that topical ABT-263 reduced markers of skin senescence and improved wound healing in aged and diabetic mouse models. Separate rodent work (2024-2025) showed amelioration of osteoporosis phenotypes and cognitive improvements in atherosclerotic mouse models. These animal findings are encouraging but have not been tested in controlled human trials for senolytic indications. High-dose ABT-263 was also associated with trabecular bone loss in some aged mouse experiments, underscoring the complexity of the compound's tissue-level effects.
Phase 1 oncology trials tested continuous oral dosing up to 250 mg/day on a 21-day on / 21-day off schedule. These figures come from trial protocols designed to characterize pharmacokinetics and maximum tolerated dose in supervised oncology settings with frequent platelet monitoring - they are not a recommended protocol and should not be used as one. No dosing guidance exists for senolytic or anti-aging applications in humans; all such use is entirely investigational. Consult a licensed clinician and, where applicable, an IRB-supervised trial framework before any human use.
This is general research/context information, not medical advice or a recommended protocol.
No evidence-based stacking protocols exist for ABT-263 in humans outside of the specific combination chemotherapy regimens studied in clinical trials (erlotinib, docetaxel, carboplatin/paclitaxel, rituximab). Senolytic combination strategies pairing navitoclax with dasatinib or quercetin are discussed in preclinical and translational literature but have not been validated in human trials for safety or efficacy. Any such combination is entirely speculative in humans.
NMN It To Win It. For the same cellular-aging/longevity goal, our NMN (a NAD+ precursor) is a legal supplement covering a similar mechanism.
See our recommended pickOrder your own bloodwork online — hormone, metabolic and inflammation panels, no doctor visit needed. Know your baselines before and during any protocol. Independent bloodwork is the cheapest insurance there is.
Get tested with Ulta Lab Tests →Both are BH3-mimetics developed from the same Abbott program, but venetoclax selectively inhibits BCL-2 only, while navitoclax also inhibits BCL-xL and BCL-w. BCL-xL is required for platelet survival; its inhibition by navitoclax causes dose-limiting thrombocytopenia. Venetoclax avoids this by sparing BCL-xL, which allowed it to reach FDA approval in CLL and AML. Navitoclax's broader target profile may matter in tumor types with BCL-xL-dependent resistance, but the platelet liability has blocked licensure.
No. ABT-263 is not FDA-approved for any indication and is not available by prescription. It exists only as an investigational compound studied in clinical trials (all completed or terminated as of available records) and as a research-grade chemical sold for laboratory use. It is not lawfully administered to humans outside of an approved clinical trial or compassionate use framework.
Senolytics are compounds that selectively eliminate senescent cells - cells that have permanently exited the cell cycle and accumulate with age, secreting inflammatory factors that contribute to tissue dysfunction. Senescent cells upregulate BCL-2 family survival proteins to resist apoptosis. ABT-263's BCL-2/BCL-xL inhibition disrupts this resistance, causing senescent cells to undergo apoptosis. Preclinical studies in aged mice have demonstrated clearance of senescent cells in skin, bone, vasculature, and brain with associated functional improvements. These findings are promising but have not been confirmed in human trials for senolytic endpoints.
This question cannot be answered here and should not be answered by any source that lacks a clinical relationship with you. ABT-263 is not approved for any human use. Human pharmacokinetic data come exclusively from supervised oncology trials with mandatory platelet monitoring. The dose-limiting toxicity (platelet suppression) requires laboratory surveillance to manage safely. If you are interested in senolytic therapies, consult a physician or seek enrollment in a registered clinical trial.
The primary barrier is thrombocytopenia. BCL-xL is essential for platelet survival, and ABT-263's inhibition of BCL-xL produces dose-dependent, concentration-dependent platelet reductions that constrain the dose achievable without unacceptable bleeding risk. At doses limited by platelet toxicity, single-agent antitumor efficacy in Phase 2 SCLC trials was insufficient for registration. The field pivoted to venetoclax (BCL-2 selective) for BCL-2-dependent malignancies. Research into mitigating the platelet liability - including topical delivery, intermittent dosing, and BCL-xL-sparing combination strategies - continues.
As of available records through mid-2026, completed human trials of ABT-263 were all in oncology contexts (CLL, SCLC, lymphoma, combination chemotherapy). Dedicated human trials of navitoclax for senolytic or anti-aging indications had not been completed and published. Translational senolytic work through 2024-2026 remains in animal models. ClinicalTrials.gov should be searched directly for current trial status, as the landscape is evolving.
Medical & legal disclaimer. This site is for informational and harm-reduction purposes only. It is not medical advice and is not a substitute for a licensed healthcare professional. The compounds discussed are largely not approved by the FDA for human use and many are sold strictly as research chemicals 'not for human consumption.' Nothing here is an endorsement to purchase, possess, or use any substance. Laws vary by jurisdiction. Always consult a qualified physician and follow the law where you live.
Some links on this page may be affiliate links. If you buy through them we may earn a commission at no extra cost to you. This never changes the safety information we publish.