SANA (MVD1)

An orally dosed nitroalkene derivative of salicylate — not a peptide — reported to raise energy expenditure by activating creatine-dependent thermogenesis in adipose tissue, with one completed Phase 1 trial and no marketing authorization anywhere.

Also referenced as: MVD1, MVD-1, salicylic acid nitroalkene, 5-(2-nitroethenyl)salicylic acid, 2-hydroxy-5-(2-nitroethenyl)benzoic acid

Also appears in: Metabolic · Other

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What is SANA (MVD1)?

SANA is 5-(2-nitroethenyl)salicylic acid (C9H7NO5, 209.16 g/mol; PubChem CID 54133300), a small molecule made by attaching an electrophilic nitroalkene group to the 5-position of salicylic acid — the same century-old scaffold behind aspirin and salsalate. It is not a peptide: it contains no amino acids and no peptide bonds, and the published route makes it in a single synthetic step (~93% yield) rather than by solid-phase assembly. “MVD1” is the code its sponsor, Eolo Pharma, used for clinical development; the two names refer to the same molecule.

It reaches research-compound catalogs on the strength of a single 2025 Nature Metabolism paper, which reported that SANA drives weight loss in obese mice and produced roughly 3% weight loss over 15 days in a Phase 1 trial — through creatine-dependent thermogenesis, a mechanism with no marketed drug behind it and no appetite-suppression component. Oral non-peptide metabolic compounds already share vendor shelves with injectable peptides, as with 5-Amino-1MQ and SLU-PP-332, and SANA has followed the same route.

How it works

• Creatine-dependent thermogenesis, not appetite suppression — in diet-induced obese mice, SANA raised creatine content in both inguinal white and brown adipose tissue, raised mitochondrial creatine kinase activity in brown fat, and upregulated Ckmt1 and Ckm in white fat, Ckm and Ckmt2 in brown fat, plus Gatm (the rate-limiting enzyme of creatine synthesis), Cidea, Prdm16, and Ppargc1a. Total food consumption was unchanged. The effect was lost after creatine depletion, and Ckmt1-knockout mice lost SANA’s glucose-lowering effect entirely (Cal, Leyva et al., Nature Metabolism, 2025, 7(8):1550–1569)
• UCP1-independent, and not a direct uncoupler — UCP1 protein levels were unchanged (Ucp1 mRNA was actually reduced in white fat and unaltered in brown fat), and the GDP-inhibited and oleate-stimulated components of brown-fat mitochondrial respiration attributable to UCP1 were unaffected. The authors state explicitly that SANA “does not directly uncouple mitochondria,” which separates it from its own scaffold: salsalate/salicylate is itself a mitochondrial uncoupler (Smith et al., Diabetes, 2016, 65(11):3352–3361; Cal, Leyva et al., 2025)
• AMPK-independent — SANA does activate AMPK, at doses similar to salicylate, but the metabolic benefit does not require it: SANA protected AMPKα1-knockout mice against diet-induced obesity and glucose intolerance, and worked at doses where the parent salicylate had no effect at all (Cal, Leyva et al., 2025)
• The reactive nitroalkene is required, and the target is unknown — the saturated circulating metabolite M1, 5-(2-nitroethyl)salicylic acid, had no effect on obesity or glucose handling in mice, and the 3- and 4-position isomers (3-SANA, 4-SANA) and an extended-chain analog (E-SANA) produced no thermogenic effect. SANA undergoes Michael addition with low-molecular-weight thiols including reduced glutathione, the reactivity signature of the nitroalkene class this group has worked on in other scaffolds (for example the nitroalkene–α-tocopherol analog in Rodríguez-Duarte et al., British Journal of Pharmacology, 2019, 176(6):757–772). But the paper states plainly that “the molecular target of SANA remains to be determined”

Research status

The published human and animal literature on SANA is, at present, one peer-reviewed paper. Everything below comes from it or from the surrounding pathway literature.

The primary paper. Cal K, Leyva A, et al., with Chini, Batthyány, and Escande as senior authors, published “A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss” in Nature Metabolism, 2025, 7(8):1550–1569. A 2023 Research Square preprint (rs.3.rs-3101395; PMID 37502859) is the same work before peer review, not an independent replication — and it is not interchangeable with the published version: the preprint reported that SANA binds creatine kinases CKMT1/2, a direct-binding claim that does not appear in the peer-reviewed paper, which instead says the molecular target is undetermined. Vendor copy quoting a “confirmed binding target” is quoting the preprint.

Preclinical work. In prevention experiments, oral SANA mixed into high-fat chow at 400 mg/kg/day for 8 weeks reduced weight gain, fat mass across all depots, liver steatosis, transaminases, fasting glucose, insulin, and HOMA-IR, and normalized glucose tolerance to lean-control levels. In a treatment model — 200 mg/kg/day started after 5 weeks of high-fat feeding had already established obesity — treated mice lost weight with cumulative food intake unaffected, though the food-intake measurements underpinning the “not appetite suppression” claim ran at very small group sizes (n = 4 in the prevention study, n = 2 in the treatment study). SANA had no effect on body weight in normal-chow mice. Once-daily subcutaneous dosing at 20 mg/kg/day reproduced the oral effects. A notable safety observation: Ckmt1-knockout mice treated with SANA showed roughly a 50% increase in mortality rate within a week at standard housing temperature, with no deaths in wild-type animals; thermoneutral housing rescued it.

The Phase 1A/B trial. Registered as ACTRN12622001519741 and run at the CMAX Clinical Research Facility in Adelaide, Australia, this was a randomized, double-blind, placebo-controlled first-in-human study in 41 volunteers. Part A gave single ascending doses of 200, 400, or 800 mg to 17 healthy lean volunteers; Part B gave multiple ascending doses of 100, 150, or 200 mg every 12 hours (200–400 mg/day) for 15 days to 24 volunteers with overweight or obesity, in an inpatient setting on a provided high-carbohydrate diet (250–300 g/day) eaten ad libitum. The primary endpoint was safety and tolerability; body weight, glucose, and insulin were exploratory.

Trial outcomes, including the negative ones. Two participants had adverse events judged definitively drug-related — reversible renal tubular damage, evidenced by proteinuria and glucosuria — both in the highest single-dose cohort, 800 mg. The Safety Review Committee ended dose escalation in Part A on the basis that the no-observed-adverse-effect level had been established, and the final planned participant in that cohort was never dosed. No definitively drug-related adverse events occurred in Part B; the most frequent possibly-related events were headache and soft stools, and no severe adverse events were recorded. Pharmacokinetics on day 15 were comparable to day 1, indicating no accumulation. On the exploratory endpoints, the top multiple-dose cohort (200 mg every 12 hours, n = 6) lost about 3% of body weight over 15 days against placebo (n = 3), with improvements in fasting glucose, insulin, HOMA-IR, and fructosamine — though one participant in that cohort did not show the fasting-glucose improvement the other five did. The comparison the authors draw to semaglutide over the same interval is against published trial data (Wilding et al., NEJM, 2021), not a head-to-head arm.

What has not happened. No Phase 2 trial appears in ClinicalTrials.gov or the WHO ICTRP portal as of August 2026, and ClinicalTrials.gov returns no record for MVD1 or for the sponsor, meaning there is no U.S. IND-registered study in the public registry — though the sponsor has publicly stated it intends to run a Phase 2 in type 2 diabetes. There is no independent replication of the thermogenic mechanism by a group outside the originating collaboration, and no published human data beyond 15 days.

The pathway itself is contested. Creatine-driven substrate cycling in fat was proposed by Kazak et al. (Cell, 2015, 163(3):643–655) and developed further with creatine kinase B as the cycling enzyme (Rahbani et al., Nature, 2021, 590(7846):480–485; Rahbani et al., Cell Metabolism, 2024, 36(3):526–540), and more recent work has placed the cycle in classical brown fat (Bunk et al., Nature Communications, 2025, 16:3221). Nicholls and Brand argued from bioenergetic first principles that the evidence for a quantitatively significant futile creatine cycle is not convincing (Nature Metabolism, 2023, 5(1):21–28). Two tensions sit inside the SANA paper itself: its gene-expression pattern does not cleanly phenocopy cold-induced activation of the pathway, and the kinases SANA upregulates (CKMT1, CKM, CKMT2) are not CKB — which, as the authors acknowledge, is the only creatine kinase isoform genetically demonstrated to carry this activity in adipocytes and thermogenic-fat mitochondria.

Common dosage forms

• Research-market capsules — dry-fill oral capsules, commonly listed at 50 mg per capsule in bottles of 60. Oral capsules remain unusual in a market dominated by injectables, and match SANA’s route in the clinical trial.
• Bulk loose powder — listed in gram quantities (5 g is a common unit), with identity and purity referred to a batch-specific certificate of analysis rather than a fixed stated figure.
• No injectable presentation — no lyophilized vial or reconstitution format is standard for this compound. The subcutaneous route used in mice required a co-solvent vehicle (100 mM phosphate buffer at pH 6.5 combined 50:50 with PEG 400), not a simple bacteriostatic-water reconstitution.
• No pharmaceutical product exists — the material used in the Phase 1 trial was a sponsor-manufactured oral formulation that has never been commercially available. Nothing sold on the research market is that product.

Key considerations

• Not a peptide, and not approved anywhere. SANA is a 209 Da synthetic small molecule, categorized alongside peptides only by vendor convention. It has no marketing authorization in any jurisdiction, no approved brand name, and no recognized status as a dietary ingredient. Its clinical program consists of one completed Phase 1 study.
• The one confirmed safety signal is renal, and it appeared quickly. Reversible tubular damage — proteinuria and glucosuria — occurred in two participants at a single 800 mg dose, and was enough for the trial’s safety committee to stop escalating. The doses that were tolerated were tested for 15 days in 24 people. Nothing in the published record speaks to longer exposure, higher cumulative dose, or use outside a monitored inpatient setting.
• Identity matters more here than purity does. The saturated metabolite and the 3-, 4-, and extended-chain analogs were all inert in the mouse thermogenesis models. A certificate reporting only a mass or a generic purity percentage does not establish that a given lot is the 5-position nitroalkene rather than a positional isomer or a reduced form — and the reduced form is what the body produces from SANA anyway.
• The efficacy evidence is a six-person exploratory endpoint. The ~3% figure comes from one dose cohort of six people against three placebo recipients, in a study explicitly designed and powered for safety rather than efficacy, over 15 days in an inpatient setting. The paper’s own limitations section calls for a Phase 2 with longer treatment, a larger sample, and extended measurements before efficacy can be claimed.
• Naming confusions are easy to make. “SANA” collides with a large number of unrelated acronyms, brand names, and words, which makes casual literature searching unreliable; MVD1 is the specific clinical code. Separately, the salicylate scaffold has its own substantial human trial record — salsalate has been tested in randomized trials for type 2 diabetes (Goldfine et al., Annals of Internal Medicine, 2013, 159(1):1–12) — and that evidence does not transfer to SANA, which the authors show works through a different mechanism at doses where salicylate itself did nothing.