17-DMAG
17-Dimethylaminoethylamino-17-demethoxygeldanamycin (alvespimycin, HSP90 inhibitor)
Written by Aaron CuhaReviewed Sep 2026
Also known as: Alvespimycin, KOS-1022, 17-DMAG hydrochloride, BMS-826476, NSC 707545
An HSP90 inhibitor that failed to extend mouse lifespan by the Interventions Testing Program's protocol test and showed a 7 to 9 percent male median gain by the Gehan test, and that extended healthspan in a progeroid mouse as one of the first senolytics identified. In people it went through oncology phase 1 trials with cardiac, ocular and one treatment-related death as dose-limiting events, and development stopped around 2010.
Overview
17-DMAG (alvespimycin) is a water-soluble derivative of geldanamycin that inhibits heat shock protein 90, the chaperone that stabilises many oncogenic signalling proteins. It was developed as a cancer drug by Kosan Biosciences and then Bristol-Myers Squibb, reached phase 1 in solid tumours, acute myeloid leukaemia and HER2-positive breast cancer, and was not taken further. It appears on this site for two reasons: a 2017 screen identified HSP90 inhibitors as a new class of senolytic drugs and used 17-DMAG to extend healthspan in a progeroid mouse, and the NIA Interventions Testing Program tested it for lifespan.
In people, three phase 1 trials define the record. Weekly intravenous 17-DMAG in 25 patients with advanced solid tumours escalated from 2.5 to 106 mg/m2; at 106 mg/m2 two of four patients had dose-limiting toxicity including one treatment-related death, none occurred at 80 mg/m2, and common adverse events were gastrointestinal, liver function changes and ocular. Twice-weekly dosing in 24 evaluable patients with advanced acute myeloid leukaemia found a maximum tolerated dose of 24 mg/m2, cardiac dose-limiting toxicity at 32 mg/m2 (raised troponin and myocardial infarction), and complete remission with incomplete count recovery in 3 of 17 evaluable patients. Combined with trastuzumab in 28 patients, dose-limiting toxicities were grade 3 left ventricular dysfunction and reversible keratitis; there was one partial response. A phase 2 in HER2-positive breast cancer was terminated after enrolling 4 patients. No trial has registered since 2010.
In mice, the Interventions Testing Program fed 17-DMAG at 30 ppm from 6 months of age in the cohort begun in 2015. In the primary report, male median lifespan was 844 against 772 days (+9 percent) with a log-rank p of 0.12, and females showed a non-significant 4 percent decrease; the ITP reported no significant change in either sex. The 2024 Gehan reanalysis, using slightly different animal counts after exclusions, put the male median gain at 7 percent with a Gehan p of 0.032 and no female effect, and noted that the effect on mortality appeared to diminish with age. Separately, in Ercc1-deficient progeroid mice, which age rapidly because of defective DNA repair, intermittent 17-DMAG extended healthspan, delayed several age-related symptoms and reduced p16INK4a expression.
17-DMAG was never approved anywhere and is not in development.
Mechanism of action
17-DMAG binds the ATP pocket of HSP90 and blocks its chaperone cycle, sending client proteins such as CDK4, HER2, AKT and mutant kinases to proteasomal degradation and inducing HSP70 as a compensatory response. In the human phase 1 trials, HSP72 induction in blood cells was detectable from 20 mg/m2 and client protein depletion at 80 mg/m2, so the target was engaged at tolerated doses. Its senolytic activity, identified in a screen of autophagy-regulating compounds using senescent Ercc1-deficient mouse fibroblasts and confirmed in human cells, is thought to work by destabilising the phosphorylated AKT that senescent cells rely on to resist apoptosis; that is cell culture and mouse work. Why an HSP90 inhibitor would reduce early deaths in male mice but not shift late survival is not explained in the ITP literature. The reanalysis authors note that two other HSP90 inhibitors extend lifespan in C. elegans.
Human evidence
Oncology phase 1 only: roughly 80 patients with advanced cancer across three published trials and several registered ones, all intravenous, all in the mid 2000s. Nobody without cancer has received 17-DMAG, no oral form exists, and no study has looked at senescence or ageing markers in a person.
- Weekly intravenous, 25 solid tumour patients: dose-limiting toxicity at 106 mg/m2 with one treatment-related death; 80 mg/m2 tolerated; gastrointestinal, liver and eye adverse events common.
- Twice-weekly intravenous, 24 AML patients: maximum tolerated dose 24 mg/m2; myocardial infarction and troponin rise at 32 mg/m2; 3 of 17 responses.
- With trastuzumab, 28 patients: heart failure and keratitis as dose-limiting toxicities; one partial response.
- Phase 2 in HER2-positive breast cancer terminated after 4 patients; a CLL phase 1 terminated; no trial registered since 2010.
- Target engagement (HSP72 induction, client protein depletion) was demonstrated in blood cells and tumour biopsies at tolerated doses, so the drug does what it is meant to in people; the question was whether that was worth the toxicity, and the sponsor's answer was no.
What this does not tell you: Cancer patients receiving intravenous cytotoxic-range doses tell you nothing about what chronic low-dose oral exposure would do in a healthy older adult, which is the only scenario relevant to the mouse findings. The cardiac and ocular toxicities are a real signal for a drug proposed for repeated senolytic dosing. No human senolytic study of any HSP90 inhibitor has been run.
Reading the research record
The NIA Interventions Testing Program runs each compound in parallel at three sites (The Jackson Laboratory, the University of Michigan and UT Health San Antonio) in genetically heterogeneous UM-HET3 mice, tests both sexes, analyses them separately, pools the sites in a site-stratified log-rank test, and publishes every result whether or not the compound worked. It is publicly funded by the National Institute on Aging with no pharmaceutical sponsorship. 17-DMAG was fed at 30 ppm from 6 months in the 2015 cohort and reported as having no significant effect on lifespan in either sex.
"Gehan-only" needs explaining because it is a weaker and more specific claim than "extended lifespan". The ITP's protocol test is the log-rank test, which weights every death equally and is most sensitive when a treatment lowers mortality by a constant proportion across the whole lifespan. In 2024 a group at UT Health San Antonio reanalysed all ITP survival data from 2004 to 2022, 132 compound by sex comparisons, with the Gehan test, which weights deaths by how many animals are still alive and so gives more weight to early and midlife deaths. Five compounds that had failed the log-rank test passed the Gehan test: metformin, enalapril and 17-DMAG in males, CAPE and green tea extract in females. The authors are explicit that this pattern is what you would expect from a compound that lowers mortality before midlife and then stops helping, that these effects are "limited to midlife and may not be effective at older ages", and no correction for the number of comparisons is reported. A Gehan-only result therefore means: fewer mice died young, the survival curves converged later, and the effect on maximum lifespan was nil.
For 17-DMAG the two reports give different median figures, 9 percent in the primary paper and 7 percent in the reanalysis, because animal counts differ slightly after exclusions for fighting and non-ageing deaths; both agree the log-rank p was 0.12 and the reanalysis puts the Gehan p at 0.032 with proportional hazards not violated. The reanalysis authors themselves flag that the effect on mortality appears to diminish at later ages. The senolytic result is in a progeroid mouse that ages fast because it cannot repair DNA, which is a model of one kind of ageing damage rather than of normal ageing, and the endpoint was healthspan, not lifespan.
Why nothing more will happen in people is straightforward. Bristol-Myers Squibb owned the drug, ran the trials, saw cardiac and ocular toxicity at active doses in a crowded HSP90 inhibitor field where no compound has reached approval for solid tumours, and stopped. The patent estate is old. A senolytic programme would need a new sponsor to take an abandoned intravenous oncology drug with a treatment-related death in its phase 1 into healthy older adults, and none has appeared. The second-generation HSP90 inhibitors that did progress are different molecules.
The evidence, charted
Fig. 1 · evidence composition
4of 7 citations (57%) 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 7 distinct years, 2008 to 2024, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. 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.
Key studies & citations
- Animal2020
Rapamycin-mediated mouse lifespan extension: late-life dosage regimes with sex-specific effects
ITP cohort begun 2015. 17-DMAG 30 ppm from 6 months: male median 844 versus 772 days (+9 percent), log-rank p = 0.12; 90th percentile +4 percent, p = 0.13. Female median -4 percent, p = 0.12. Reported as no significant change in either sex, alongside minocycline, beta-GPA and MitoQ nulls. NIA funded.
Aging Cell - Animal2024
The Gehan test identifies life-extending compounds overlooked by the log-rank test in the NIA Interventions Testing Program: metformin, enalapril, caffeic acid phenethyl ester, green tea extract, and 17-DMAG
17-DMAG 30 ppm from 6 months, 152 treated males against 264 controls: median +7 percent, log-rank p = 0.12, Gehan p = 0.032, proportional hazards assumption not violated. No female effect. Effect on mortality appears diminished at later ages. One of 132 comparisons reanalysed with no multiplicity correction reported. NIA funded.
GeroScience - Animal2017
Identification of HSP90 inhibitors as a novel class of senolytics
Screen of autophagy-regulating compounds in senescent Ercc1-deficient mouse fibroblasts identified HSP90 inhibitors as senolytic in mouse and human cells. In Ercc1-deficient progeroid mice, 17-DMAG extended healthspan, delayed onset of several age-related symptoms and reduced p16INK4a expression. Progeroid model, not normal ageing; no lifespan endpoint.
Nature Communications - Human2011
A phase I study of the heat shock protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced solid tumors
25 patients, weekly intravenous doses 2.5 to 106 mg/m2. At 106 mg/m2, 2 of 4 had dose-limiting toxicity including one treatment-related death; none at 80 mg/m2. Common adverse events gastrointestinal, liver function and ocular. HSP72 induction from 20 mg/m2, client protein depletion at 80 mg/m2. Academic UK trial with company drug supply.
Clinical Cancer Research - Human2010
Phase I study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17-DMAG) administered intravenously twice weekly to patients with acute myeloid leukemia
24 evaluable patients with advanced AML, 8 to 32 mg/m2 twice weekly. Maximum tolerated dose 24 mg/m2; cardiac dose-limiting toxicities at 32 mg/m2 (troponin elevation, myocardial infarction). Complete remission with incomplete count recovery in 3 of 17 evaluable. Company sponsored (Kosan).
Leukemia - Human2012
A phase I dose-escalation trial of trastuzumab and alvespimycin hydrochloride (KOS-1022; 17 DMAG) in the treatment of advanced solid tumors
28 patients (25 breast, 3 ovarian), 60 to 100 mg/m2 weekly with trastuzumab. Dose-limiting toxicities: grade 3 left ventricular systolic dysfunction (100 mg/m2) and reversible grade 3 keratitis in two patients (80 mg/m2). One partial response, seven stable disease in HER2-positive breast cancer.
Clinical Cancer Research - Human2008
Clinical trial of intravenous alvespimycin in patients with HER2 positive breast cancer
Phase 2, Bristol-Myers Squibb, TERMINATED after enrolling 4 participants, no results posted. The last alvespimycin trial to register started in 2010 (CLL, also terminated). Development has stopped.
ClinicalTrials.gov
Frequently asked questions
Did 17-DMAG extend lifespan in the ITP?
Not by the programme's protocol test: male median lifespan was 7 to 9 percent higher at 30 ppm from 6 months but the log-rank p was 0.12, and females showed a non-significant 4 percent decrease. The 2024 Gehan reanalysis found the male effect significant at p = 0.032 and describes it as diminishing with age. The ITP counts it as a null.
Is 17-DMAG a senolytic?
In cell culture and in a progeroid mouse, yes: a 2017 screen identified HSP90 inhibitors as a class of senolytics and 17-DMAG extended healthspan and reduced p16 expression in Ercc1-deficient mice. No human has received it as a senolytic and no HSP90 inhibitor has been tested for senescence in people.
Was it ever given to people?
Yes, intravenously to around 80 patients with advanced cancer in phase 1 trials between 2004 and 2012. Dose-limiting toxicities included myocardial infarction, heart failure, keratitis and one treatment-related death. A phase 2 was terminated after 4 patients and development stopped around 2010.
Can I buy 17-DMAG?
It is sold by research chemical suppliers for laboratory use. It has no approved form, no oral formulation, no human safety data outside intravenous oncology dosing, and documented cardiac toxicity at active doses. Nothing on this page supports taking it.