# Angiotensin-(1-7): Evidence, Mechanism, Dosing & Legal Status

> A clinical monograph on Angiotensin-(1-7) / TXA127 (talfirastide) — the effector of the protective ACE2/Mas arm of the renin-angiotensin system. Real human RCTs, a negative COVID-19 trial, and no FDA approval.

*Published 2026-06-30 · Updated 2026-07-01 · By Marcus Feld, PharmD, BCPS*

The short answer
Angiotensin-(1-7) — pharmaceutically **TXA127 / talfirastide** — is one of the few peptides on the market with a *real, registered human-trial record, including randomized controlled trials*. That is exactly why an honest grade must reckon with what those trials showed: it is **repeatedly safe (Grade B)** with a credible early hematopoietic signal, but its **best-powered RCTs in COVID-19 were clearly negative**, its oncology trials produced zero objective responses, and **no indication has a positive confirmatory Phase 3**. It is not FDA-approved and is prohibited in sport at all times under WADA.[9](https://peptidevox.com/#r9)[26](https://peptidevox.com/#r26)

Angiotensin-(1-7), also written Ang-(1-7) or A(1-7), is an endogenous seven-amino-acid peptide and the principal effector of the protective, counter-regulatory arm of the renin-angiotensin system.[1](https://peptidevox.com/#r1) Formulated as the investigational drug TXA127 (international nonproprietary name talfirastide), it has been tested in genuine clinical trials by Tarix and later Constant Therapeutics. This monograph separates what those trials proved — chiefly safety — from what they did not.

*This article is informational and editorial content for research and educational purposes only. It is not medical advice, not a protocol to follow, and not a sourcing guide. Angiotensin-(1-7)/TXA127 is an unapproved investigational compound and is prohibited in sport. Dosing figures are reported strictly as seen in the published literature and registered trials for completeness — not as recommendations. Consult a licensed clinician before any health decision.*

## What is Angiotensin-(1-7) and how does it work?

Angiotensin-(1-7) is a heptapeptide, H-Asp-Arg-Val-Tyr-Ile-His-Pro-OH (one-letter sequence DRVYIHP), comprising the first seven residues of angiotensin I/II. Its molecular formula is C41H62N12O11, molecular weight approximately 899 Da, CAS 51833-78-4; the synthetic drug carries the INN talfirastide and development code TXA127.[21](https://peptidevox.com/#r21)[22](https://peptidevox.com/#r22)[20](https://peptidevox.com/#r20) It is generated endogenously chiefly by ACE2-mediated cleavage of angiotensin II, and secondarily from angiotensin I by endopeptidases.[1](https://peptidevox.com/#r1)[3](https://peptidevox.com/#r3)

The renin-angiotensin system is a dual-axis system. The classical arm (renin to angiotensinogen to Ang I to ACE to Ang II acting at the AT1 receptor) drives vasoconstriction, oxidative stress, inflammation and fibrosis. The protective arm — ACE2 to Ang-(1-7) to the Mas receptor — opposes it; the 2003 identification of the orphan GPCR Mas as the endogenous Ang-(1-7) receptor established this axis as the counter-regulatory pole.[1](https://peptidevox.com/#r1)[2](https://peptidevox.com/#r2) At the Mas receptor, Ang-(1-7) triggers endothelial nitric-oxide and prostaglandin release (vasodilation), reduces NADPH-oxidase-derived reactive oxygen species and NF-kB activation, and suppresses pro-inflammatory cytokines.[2](https://peptidevox.com/#r2)[22](https://peptidevox.com/#r22) Its anti-fibrotic action runs through inhibition of ERK1/2 phosphorylation and the TGF-beta1/Smad pathway, blunting collagen deposition across cardiac, renal, pulmonary and hepatic fibrosis models.[1](https://peptidevox.com/#r1) A second mechanism is antiangiogenic: Ang-(1-7) lowers placental growth factor (PlGF), which underlies its first-in-class antiangiogenic anticancer rationale.[4](https://peptidevox.com/#r4) It can also act as a beta-arrestin-biased agonist at the AT1 receptor.[2](https://peptidevox.com/#r2)

Pharmacokinetically, native Ang-(1-7) has a very short half-life owing to rapid degradation by ACE (to Ang-(1-5)) and dipeptidyl peptidase-3. In humans the plasma half-life is roughly 25-37 minutes, with subcutaneous Tmax near 1 hour; in rats the IV half-life is on the order of seconds, extended by ACE inhibition.[4](https://peptidevox.com/#r4)[13](https://peptidevox.com/#r13) It is a parenteral peptide (SC or IV), is not orally bioavailable and penetrates the blood-brain barrier poorly, motivating stabilized analog and conjugate development.[14](https://peptidevox.com/#r14)

## What is the evidence by indication?

Unlike most gray-market peptides, Ang-(1-7) has more genuine human-trial experience than most marketed peptides — but the largest, best-powered RCTs were negative, the oncology trials showed biomarker signals without tumor responses, and the tissue-repair indications rest on small early-phase or preclinical data. The table below grades each indication honestly.

  Angiotensin-(1-7) / TXA127 evidence by indication

    IndicationBest evidenceGrade

    Chemotherapy-induced thrombocytopenia / myelosuppressionRandomized double-blind Phase 2b (n=34) plus earlier Phase 1/2a; multilineage recovery signalB (human, small RCT)
    Oncology (solid tumors, antiangiogenic)Phase 1 PK + Phase 2 sarcoma — safe, PlGF lowered, but zero objective responsesB safety / D efficacy
    Severe COVID-19 / acute lung injuryNIH ACTIV-4 RCT (n=343) + two further RCTs — adequately powered, NEGATIVEA-quality but negative
    Stem-cell transplant / GVHD / engraftmentTrials withdrawn for poor enrollment; no positive controlled readoutC-to-D
    Stroke recovery & DMD-associated cardiomyopathyPreclinical positive; Phase 2 ongoing, no results reportedC (pending)
    Fibrosis, cardiovascular & muscular-dystrophy protectionAnimal and in-vitro models only — basis for orphan designationsC (preclinical)

The most distinctive human signal is in chemotherapy-induced thrombocytopenia. In a randomized, double-blind, placebo-controlled Phase 2 study, 34 patients with ovarian, Fallopian-tube or peritoneal carcinoma on gemcitabine plus carboplatin/cisplatin were randomized to TXA127 100 micrograms per kilogram (n=11), 300 (n=13), or placebo (n=10). There were no grade-4 thrombocytopenia events at 100 micrograms per kilogram versus 6% of cycles on placebo (p=0.07), and recovery was multilineage across platelets, red cells and lymphocytes.[6](https://peptidevox.com/#r6)[7](https://peptidevox.com/#r7) Preclinically, Ang-(1-7) accelerated hematopoietic recovery after total-body irradiation.[8](https://peptidevox.com/#r8) It is a real, biologically plausible early signal, but small and not advanced to a positive Phase 3.

In oncology, the Phase 1 PK study in 18 patients with advanced solid tumors set a recommended Phase 2 dose of 400 micrograms per kilogram, with clinical benefit tracking decreased plasma PlGF.[4](https://peptidevox.com/#r4) The Phase 2 metastatic-sarcoma trial in 20 patients did not meet its RECIST-response endpoint — zero partial or complete responses — though 9 of 20 achieved disease stabilization beyond three months.[5](https://peptidevox.com/#r5) The pattern is consistent: safe, with a coherent antiangiogenic biomarker effect, but no objective antitumor responses.

The headline negative trial
The best-powered human testing of Ang-(1-7) was in severe COVID-19, and it failed. In the NIH ACTIV-4 Host Tissue RCT (35 US sites, TXA-127 0.5 mg/kg IV daily for five days, n=163 vs placebo n=166), oxygen-free days did not differ (adjusted OR 0.88) and 28-day mortality was 13.5% versus 13.3%. The authors concluded RAS modulation with synthetic Ang-(1-7) did not improve outcomes.[9](https://peptidevox.com/#r9)

That negative result was reinforced by a single-center pilot RCT (safe but underpowered, stopped early) and a seamless Phase 1-2 ICU RCT in which oxygen-free days did not differ significantly (median 19 vs 14 days, p=0.15).[11](https://peptidevox.com/#r11)[12](https://peptidevox.com/#r12) The full ACTIV-4 record is registered and indexed on PubMed at [pubmed.ncbi.nlm.nih.gov/37039791](https://pubmed.ncbi.nlm.nih.gov/37039791/), and the readers can confirm the mortality and oxygen-free-day figures directly.[10](https://peptidevox.com/#r10) Meanwhile, transplant and GVHD trials were withdrawn for poor enrollment, leaving no positive efficacy readout.[18](https://peptidevox.com/#r18)[19](https://peptidevox.com/#r19) Constant Therapeutics now runs active Phase 2 programs in ischemic-stroke recovery and DMD-associated cardiomyopathy (0.5 mg/kg/day SC), both supported by animal data but with no human efficacy readout yet.[16](https://peptidevox.com/#r16)[17](https://peptidevox.com/#r17) The broader anti-fibrotic, cardiovascular and muscular-dystrophy claims remain preclinical and form the basis for the orphan designations, not for proven human benefit.[1](https://peptidevox.com/#r1)[23](https://peptidevox.com/#r23)

## What doses appear in the literature?

Reported strictly as information, not a protocol; there is no FDA-approved formulation or sanctioned dose. The Phase 1 oncology study tested subcutaneous 100, 200, 400 and 700 micrograms per kilogram once daily for five days every 21 days, with 400 the recommended Phase 2 dose and 700 dose-limiting.[4](https://peptidevox.com/#r4) The metastatic-sarcoma Phase 2 used a fixed 20 mg per day subcutaneously.[5](https://peptidevox.com/#r5) Chemotherapy-thrombocytopenia trials used 100 or 300 micrograms per kilogram subcutaneously after each cycle, with the lower 100 dose carrying the cleaner signal — notably not dose-proportional.[6](https://peptidevox.com/#r6) The COVID-19 ACTIV-4 RCT used 0.5 mg per kilogram IV once daily for five days; the ICU study used continuous IV 5 micrograms per kilogram per day escalated to 10, up to seven days.[9](https://peptidevox.com/#r9)[12](https://peptidevox.com/#r12) Current Phase 2 trials use 0.5 mg per kilogram per day subcutaneously.[16](https://peptidevox.com/#r16) Because of the short half-life, trial material is dosed daily by SC or by continuous IV infusion; there is no sanctioned compounding pathway, and material sold online as a research chemical is unregulated.[24](https://peptidevox.com/#r24)

## How safe is Angiotensin-(1-7)?

Across the trial program TXA127 has been generally well tolerated. Most common were injection-site reactions (all grade 1/2 in the sarcoma trial) plus low-grade headache, fatigue, flushing, pruritus, muscle cramps and musculoskeletal pain; in the COVID RCTs safety matched placebo, with one possibly-related bradycardia on continuous IV infusion.[5](https://peptidevox.com/#r5)[4](https://peptidevox.com/#r4)[12](https://peptidevox.com/#r12) The clearest serious-event signal is thrombosis, which the Phase 1 investigators attributed to a class effect of antiangiogenic drugs: a grade-3 deep vein thrombosis occurred at 400 micrograms per kilogram and again as a dose-limiting toxicity in the sarcoma trial, and at the supratherapeutic 700 micrograms per kilogram one patient had multifocal small strokes with a vasculitic MRI pattern.[4](https://peptidevox.com/#r4)[5](https://peptidevox.com/#r5) Notably, no hypertension, bleeding or hematologic toxicity was observed, consistent with a non-pressor peptide.[4](https://peptidevox.com/#r4)

Theoretical risks deserve respect. Cancer biology is double-edged: Ang-(1-7) is antiangiogenic and was developed as an anticancer agent, yet Mas signaling is context-dependent and some preclinical reports describe proliferative effects, such as stimulation of lung bronchoalveolar progenitors, so blanket pro-regenerative claims should be cautious.[15](https://peptidevox.com/#r15) As a vasodilator it could theoretically lower blood pressure, though trials showed no meaningful mean change at studied doses.[12](https://peptidevox.com/#r12) Pregnancy and lactation lack safety data and should be avoided, patients at high thrombotic risk warrant caution, and long-term safety beyond weeks to months is uncharacterized.[4](https://peptidevox.com/#r4) ACE inhibitors prolong Ang-(1-7) exposure, a pharmacologic interaction to note.[13](https://peptidevox.com/#r13)

## What is the FDA and WADA status in 2026?

Angiotensin-(1-7)/TXA127/talfirastide is not FDA-approved for any indication and remains investigational.[24](https://peptidevox.com/#r24) It holds multiple Orphan Drug Designations — including pulmonary arterial hypertension, myelodysplastic syndrome, enhancement of stem-cell-transplant engraftment, Duchenne muscular dystrophy, limb-girdle muscular dystrophy and dystrophic epidermolysis bullosa — plus a Rare Pediatric Disease designation for recessive dystrophic epidermolysis bullosa.[23](https://peptidevox.com/#r23)[20](https://peptidevox.com/#r20) These are development incentives such as exclusivity, fee relief and expedited channels — not marketing approval and not a statement of safety for general use. No NDA or BLA has been approved.

It is not an approved 503A patient-specific or 503B outsourcing-facility product and does not appear on FDA's bulk-substance lists for legal compounding. FDA's 2023 warning letters to peptide sellers and 2024 clarification that many clinic-marketed peptides are not approved and cannot be legally compounded apply to this class; clinics offering it operate against federal guidance.[25](https://peptidevox.com/#r25)[24](https://peptidevox.com/#r24) There is no EU marketing authorization either.[23](https://peptidevox.com/#r23) For athletes the picture is unambiguous: because Ang-(1-7)/TXA127 is not approved for human therapeutic use by any regulator, it falls under category S0 (Non-Approved Substances) of the WADA Prohibited List and is prohibited at all times, in and out of competition.[26](https://peptidevox.com/#r26)[25](https://peptidevox.com/#r25) The list is non-exhaustive and explicitly captures research-use-only substances; the live WADA list should be re-verified before any competition reliance.

**Bottom line.** Angiotensin-(1-7) is mechanistically one of the most interesting peptides in clinical development and, unlike most gray-market peptides, has a real registered human-trial record including RCTs. What is reasonably supported is narrow: it is repeatedly safe, produces a credible multilineage anti-thrombocytopenia signal after chemotherapy, and reliably lowers the antiangiogenic biomarker PlGF — Grade B. What is not proven, and in key cases disproven, is broader: its best-powered RCT in COVID-19 was clearly negative, the oncology trials produced zero objective responses, several transplant trials were withdrawn, and the cardiovascular and regenerative indications rest on animal data or unread Phase 2 trials. It is not FDA-approved (orphan designations only), has no legal compounding pathway, and is WADA-prohibited under S0 — proven mainly to be safe, not yet proven to work for any approved use. Regulatory facts here are current as of June 2026 and should be re-verified after that date.

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Source: https://peptidevox.com/peptide-encyclopedia/angiotensin-1-7
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