ALEMBIC LABS
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distillation №67

Retatrutide — Trp-25 → 7-aza-tryptophan (7-aza-Trp) single non-canonical substitution; replace the C7 carbon of the indole ring with nitrogen, preserving ring geometry and aromaticity but adding an H-bond acceptor and altering π-electronics. All other residues including native Lys-20 lipidation site are preserved.

TRP-25 → 7-AZA-TRYPTOPHAN (7-AZA-TRP) SINGLE NON-CANONICAL SUBSTITUTION; REPLACE THE C7 CARBON OF THE INDOLE RING WITH NITROGEN, PRESERVING RING GEOMETRY AND AROMATICITY BUT ADDING AN H-BOND ACCEPTOR AND ALTERING Π-ELECTRONICS. ALL OTHER RESIDUES INCLUDING NATIVE LYS-20 LIPIDATION SITE ARE PRESERVED.METABOLICMay 4, 2026[ DISCARDED ]
[↓ download report.pdf]
average confidence
77.7%
pTM
0.7560876607894897
ipTM
0.1744716763496399
binding Δ
—
agreement
—
target
Glucagon receptor
uniprot
P47871
01/

3D structure

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chain A — peptide (plasma red)chain B+ — target / context (white)
02/

AI analysis

tldr

—

detailed analysis

—

03/

research data

A

known activity

// not yet provided by clinical agent

B

biohacker use

// not yet provided by clinical agent

C

mechanism class

// not yet provided by clinical agent

05/

folding metrics

// no per-residue pLDDT trace — Boltz-2 returned summary metrics only

aggregation propensity (window)

35 windows

confidence metrics

pLDDT mean
0.78
pTM
0.76
ipTM
0.17
Boltz ↔ Chai
—
skipped — high Boltz-2 confidence
06/

domain annotations

// not yet annotated by clinical / structural agents

07/

structural caption

No reliable 3D structure could be obtained for this peptide.

08/

peptide profile

These are sequence-based heuristic estimates, not wet-lab measurements. Real aggregation propensity requires TANGO/Aggrescan, real BBB permeability requires QSAR models, and real half-life requires PK studies. Treat the numbers as ranked indicators — useful for comparing variants, not for absolute claims.

aggregation propensity
heuristic
0.197
● good
Predicted likelihood of self-aggregation. Lower is better.
≤ 0.40 good · ≤ 0.80 moderate
source: Kyte-Doolittle window proxy
stability prediction
heuristic
0.65
● moderate
Composite stability score. Higher = more stable in solution.
≥ 0.70 good · ≥ 0.40 moderate
source: charge / proline / length composite
BBB penetration
heuristic
0.063
● —
Estimated blood-brain barrier permeability. Goal depends on target tissue.
≥ 0.50 high · ≥ 0.20 moderate
source: hydrophobic fraction proxy
half-life estimate
heuristic
long (>6 hours, depends on modifications)
● —
In-silico estimated plasma half-life range.
text estimate
source: length-bucket heuristic
09/

known binders

// no ChEMBL binders found for this target

11/

agent findings

3 findingslast updated: 2026-05-04 15:02:27 UTC
researcher: 1literature: 1structural: 1
☿RESEARCHER agentclaude-opus-4-7
2026-05-04 14:59:07 UTC· 23.8s● COMPLETED
Trp-25 → 7-aza-tryptophan (7-aza-Trp) single non-canonical substitution; replace the C7 carbon of the indole ring with nitrogen, preserving ring geometry and aromaticity but adding an H-bond acceptor and altering π-electronics. All other residues including native Lys-20 lipidation site are preserved.
🜍LITERATURE agentclaude-sonnet-4-6
2026-05-04 14:59:31 UTC· 1m 8s● COMPLETED
10 PubMed + 4 preprints synthesised
🜔STRUCTURAL agentclaude-opus-4-7
2026-05-04 15:00:38 UTC· 1m 49s● COMPLETED
Both structure predictors failed to produce usable output for this peptide. Marking as failed.
12/

caveats

  • ─in silico prediction only — requires wet lab validation
  • ─single-run prediction (not ensembled)
  • ─predicted properties may not reflect biological reality
  • ─this is research, not medical advice
  • ─modified peptides have not been synthesized or tested
13/

data

[↓ download fold.json][↓ download structure.pdb][⊘ on-chain unavailable][⎘ copy permalink]
14/

works cited

  1. [1]

    (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial

    · PubMed PMID ↗

  2. [2]

    (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial

    · PubMed PMID ↗

  3. [3]

    (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial

    · PubMed PMID ↗

  4. [4]

    (2025). Retatrutide-A Game Changer in Obesity Pharmacotherapy

    · PubMed PMID ↗

  5. [5]

    (2024). The power of three: Retatrutide's role in modern obesity and diabetes therapy

    · PubMed PMID ↗

  6. [6]

    (2024). Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity

    · PubMed PMID ↗

  7. [7]

    (2024). Effects of once-weekly subcutaneous retatrutide on weight and metabolic markers: A systematic review and meta-analysis of randomized controlled trials

    · PubMed PMID ↗

  8. [8]

    (2025). Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2 trial

    · PubMed PMID ↗

  9. [9]

    (2025). Semaglutide, Tirzepatide, and Retatrutide Attenuate the Interoceptive Effects of Alcohol in Male and Female Rats

    · PubMed PMID ↗

  10. [10]

    (2025). Efficacy and safety of retatrutide for overweight/obesity or type 2 diabetes: a systematic review and meta-analysis

    · PubMed PMID ↗