BPTES
BPTES, allosteric inhibitor of glutaminase 1 (GLS1)
Written by Aaron CuhaReviewed Sep 2026
Also known as: bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide
The tool compound behind a distinct senolytic idea: senescent cells run on glutamine to neutralise their own acidity, so blocking glutaminase kills them. Demonstrated in mice and cells. BPTES itself has never been given to a person.
Overview
The glutaminolysis route to senolysis was set out in Science in 2021. Lysosomal membrane damage lowers the internal pH of senescent cells, which induces kidney-type glutaminase; the resulting glutaminolysis produces ammonia that neutralises the acidity and keeps the cell alive. Blocking glutaminase 1 removes that buffer. In aged mice, inhibiting kidney-type glutaminase eliminated senescent cells specifically and improved age-associated organ dysfunction.
BPTES is the allosteric GLS1 inhibitor used to test this. In senescent human kidney tubular cells and in aged mice, BPTES eliminated senescent tubular cells by driving excessive opening of the mitochondrial permeability transition pore through upregulation of mitofusin 1, and ameliorated age-associated kidney disease in the mice. In mesenchymal stem cells worn out by repeated culture, short-term BPTES reduced p16, p21 and senescence-associated secretory genes and restored proliferation and therapeutic activity, with downstream effects in mdx mice.
BPTES has no human data of any kind. It is a laboratory compound with poor drug-like properties, which is why the clinical-stage work in this class was done with telaglenastat, an orally bioavailable GLS1 inhibitor that reached randomised oncology trials. No senolytic has improved a clinical outcome in a randomised trial in humans, and the glutaminase route has never been tested against a senescence endpoint in a person.
Mechanism of action
Established in human cells and mice: senescent cells have lowered intracellular pH from lysosomal membrane damage, which induces kidney-type glutaminase and the ammonia production that buffers it. BPTES binds GLS1 allosterically and blocks that. In senescent kidney tubular cells the downstream event is upregulation of mitofusin 1, a shift from mitochondrial fission to fusion, and excessive opening of the mitochondrial permeability transition pore. Whether any of this is true of senescent cells in a living human is unknown.
Human evidence
None for BPTES. No human has received it in a published study and no trial is registered. Human data for glutaminase inhibition come from telaglenastat, a different molecule, in cancer patients.
What this does not tell you: Because BPTES has never been dosed in a person, its human pharmacokinetics, tolerated dose and off-target effects are unknown. Glutamine metabolism is not confined to senescent cells, and what systemic glutaminase inhibition does over months in a person has only been examined in cancer trials of a different compound, where grade 3 to 4 adverse events were common in both arms.
Reading the research record
The glutaminolysis idea is mechanistically distinct from the BCL-2 family senolytics, and that is its interest: it proposes that senescent cells have a metabolic dependency rather than an apoptotic one. The Science paper is a strong piece of mouse and cell biology and has been followed by organ-specific mouse work in kidney and in stem cell ageing.
None of it is human. The compound that could test the idea in people, telaglenastat, went into oncology and its pivotal randomised trial missed its primary endpoint. Nobody has run a glutaminase inhibitor trial with a senescence endpoint in a person, and BPTES is not a candidate to be that compound.
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 4 distinct years, 2021 to 2025, 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
- Animal2021
Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders
Human cells and mice. GLS1 was identified as essential for the survival of human senescent cells: lysosomal damage lowers intracellular pH, inducing kidney-type glutaminase, whose ammonia production neutralises the acidity. Inhibiting it in aged mice eliminated senescent cells specifically and ameliorated age-associated organ dysfunction.
Science - Animal2025
Senolysis by GLS1 Inhibition Ameliorates Kidney Aging by Inducing Excessive mPTP Opening Through MFN1
Human HK-2 kidney cells made senescent with d-galactose, plus aged mice. BPTES eliminated senescent tubular cells through mitofusin 1 upregulation and excessive mitochondrial permeability transition pore opening, and ameliorated age-associated kidney disease in the mice.
Journals of Gerontology Series A - Animal2024
Glutaminase-1 inhibition alleviates senescence of Wharton's jelly-derived mesenchymal stem cells via senolysis
Human Wharton's jelly mesenchymal stem cells in culture, plus mdx mice. Short-term BPTES reduced p16, p21 and senescence-associated secretory genes and restored proliferation; the treated cells enhanced muscle formation and reduced fibrosis in the mice.
Stem Cells Translational Medicine - Human2022
Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial
The only randomised human data on glutaminase inhibition. 444 patients with metastatic renal cell carcinoma. Median progression-free survival 9.2 months with telaglenastat plus cabozantinib versus 9.3 months with placebo plus cabozantinib, hazard ratio 0.94, P = 0.65. Manufacturer funded. Oncology, not senescence.
JAMA Oncology - Human2022
Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial
69 patients randomised 2:1. Median progression-free survival 3.8 months versus 1.9 months, hazard ratio 0.64, one-sided P = 0.079 against a pre-specified one-sided alpha below 0.2. Grade 3 to 4 events in 74 percent versus 61 percent. Manufacturer funded.
Clinical Cancer Research
Frequently asked questions
Has BPTES been given to humans?
No. No published study has administered it to a person and no trial is registered. It is a laboratory tool compound.
Why would blocking glutaminase kill senescent cells?
Because of an acidity problem. Senescent cells have damaged lysosomal membranes and a lowered internal pH, and they induce kidney-type glutaminase so that glutamine breakdown produces ammonia to neutralise it. Removing that buffer kills them. This was shown in human cells and aged mice.
Is there a version of this drug that people have taken?
Telaglenastat, an oral glutaminase inhibitor, has been given to hundreds of cancer patients in randomised trials. Its pivotal trial in 444 people with kidney cancer showed no progression-free survival benefit. No glutaminase inhibitor trial has used a senescence endpoint in a person.