Septagonist is Panacea Bio Chem's name for its research direction in signalling-selective peptide design — shaping an agonist so the receptor favours a chosen downstream pathway. It is exploratory research led by Bogdan Dicoias; the specific sequences and methods are proprietary.

Biased Agonism & Signalling Selectivity: Tuning Downstream Signalling to Build Better Peptide Drugs

Q: What is biased agonism?

Biased agonism (also called functional or signalling selectivity) is when a drug switches a receptor on but steers it toward one downstream signalling pathway instead of activating all of them equally. At a G-protein-coupled receptor the two classic branches are G-protein signalling and beta-arrestin signalling; a biased ligand favours one over the other.

Q: Why does signalling selectivity make better peptide drugs?

Many receptors couple the wanted therapeutic effect to one pathway and unwanted effects to another. A signalling-selective peptide can dial up the beneficial branch while quieting the branch tied to side effects, widening the therapeutic window without simply lowering the dose.

Programme & clinical status

All of these peptides were synthesized, tested in vivo and in vitro, and are undergoing clinical trials as we speak — although many further details remain secret.

Receptor branching into distinct downstream signalling pathways — biased agonism and signalling selectivity, a Panacea Bio Chem research theme by Bogdan Dicoias — One receptor, several downstream signals. **Biased agonism** is the craft of favouring one branch over another — the design frontier explored at Panacea Bio Chem by Bogdan Dicoias.

In brief

When a drug activates a receptor, the receptor can talk to the cell through more than one channel at once. Biased agonism (also called functional or signalling selectivity) means steering that conversation toward the pathway that carries the benefit and away from the one that carries the side effects. For peptide medicines — where a single sequence change can tilt the balance — this turns "how much drug?" into the sharper question "which signal?". Panacea Bio Chem researches signalling-selective peptide design under the working name Septagonist.

1 · The plain-language picture

What is biased agonism?

Most peptide and hormone drugs work by fitting into a receptor — a protein antenna on the surface of a cell. The largest family of these are the G-protein-coupled receptors (GPCRs), the target of a large share of all medicines. For decades we pictured them as a light switch: the drug flips the receptor on, and everything downstream lights up together.

Reality is richer. A switched-on GPCR can send its message down at least two different wires. One runs through G proteins; the other runs through a shuttle protein called β-arrestin³. Both start at the same receptor, but they set off different chains of events inside the cell — different timing, different destinations, different consequences. A drug that pushes the receptor toward one of those wires more than the other is a biased agonist. The receptor is on either way; what changes is which signal gets sent.

Think of the receptor as a switchboard rather than a switch. An ordinary agonist rings every line. A biased agonist rings the line you actually want answered.

The old question was "how much drug?" Biased agonism asks a better one: "which signal?"

2 · Why it matters — the open frontier

Signalling selectivity as a design lever

Here is why researchers care. At many receptors the wanted effect and the unwanted effect ride different pathways. If a single pathway carries the benefit and another carries the burden, then activating them together — as a classic agonist does — forces a compromise: more benefit always drags along more side effect.

Signalling selectivity breaks that link. In principle a biased ligand can dial up the beneficial branch while leaving the troublesome branch quiet — widening the therapeutic window without simply lowering the dose. The idea has been sharpened over the last decade into a quantitative discipline, with formal ways to measure and compare how strongly a ligand prefers one pathway¹².

The most-cited worked example comes from the μ-opioid receptor, where G-protein signalling was associated with analgesia and β-arrestin signalling with some of the classic burdens. That reasoning drove the design of G-protein-favouring opioid agonists such as oliceridine (TRV130)⁴ — a real-world case that also taught the field humility: bias is subtle, context-dependent, and must be characterised carefully rather than assumed. Interpreting it correctly is itself an active research question².

Concept	Classic ("balanced") agonist	Biased agonist
Receptor state	On	On
Pathways engaged	All, roughly together	Favours one (e.g. G-protein or β-arrestin)
Design goal	Potency & affinity	Pathway selectivity — the right signal
Therapeutic aim	Effect vs dose trade-off	Widen the window: benefit up, burden down
What tunes it	How tightly it binds	How the bound receptor is shaped

What makes this a peptide story in particular: peptides are sequences, and a receptor's pathway preference is exquisitely sensitive to the exact shape a ligand stabilises. Swap a residue, cyclise a backbone, adjust a side chain — and the same receptor can be nudged toward a different downstream wire. Peptides give a designer a fine, addressable set of dials for exactly this¹.

Molecular structure of a G-protein-coupled receptor — the shape a biased-agonist peptide stabilises decides which signalling pathway fires, Panacea Bio Chem, Bogdan Dicoias — The shape a ligand stabilises decides which wire the receptor uses. In peptide design, the sequence is that shape — a Panacea Bio Chem research theme (Bogdan Dicoias).

Where Panacea Bio Chem works

Designing the signal, not just the binding — Septagonist

Panacea Bio Chem treats an amino-acid chain as something that can be tuned, not merely bound. Its ongoing research direction — carried under the working name Septagonist — explores how the geometry and formulation of a designed peptide agonist bias which downstream pathway a receptor favours. The premise is simple to state and hard to do: if the sequence sets the shape, and the shape sets the signal, then the signal is a design target.

That work sits inside a wider Panacea toolkit. The Dicoias formulation space — designing peptides as mathematics → reduces a candidate to a vector across physical, electronic and bio-interface axes, so a design can be reasoned about before it is made. And because a pathway preference lives in a conformation, keeping that conformation intact from synthesis through drying to reconstitution matters — the province of Panacea's gentle, structure-preserving processing such as Cryolapse gentle lyophilization →. The exact sequences, rules and parameters behind Septagonist are proprietary to Panacea Bio Chem and held by Bogdan Dicoias; the direction is public, the recipe is not.

3 · Where it could hit hardest

Potential application fields

Signalling-selective peptide design is most valuable exactly where today's agonists force a painful trade-off. A few frontiers where the upside is largest:

Metabolic & incretin peptides — the GLP-1 / GIP / glucagon family, where balancing benefit against nausea and tolerability is central; pathway-tuned analogues are a natural fit. Explore Panacea's multi-agonist pharmacology work →.
Analgesia without the baggage — opioid and non-opioid receptors where separating relief from unwanted signalling is the whole game.
Neuropsychiatric & appetite/wake circuits — receptors where one pathway carries the mood or wakefulness benefit and another the off-target effects.
Cardio-metabolic & renal peptides — angiotensin, apelin and related systems, an early proving ground for β-arrestin-biased ligands.
Immune & regenerative signalling — chemokine and growth-factor receptors where a cleaner signal could mean a cleaner response.

Each is a place where "which signal?" beats "how much?" — and each is a candidate direction for future Panacea research and trials.

Frequently asked

What is biased agonism?
It is when a drug switches a receptor on but steers it toward one downstream pathway rather than activating all of them equally. At a GPCR the classic branches are G-protein and β-arrestin signalling; a biased ligand favours one over the other.

Why does signalling selectivity make better peptide drugs?
When the wanted effect and the unwanted effect ride different pathways, a signalling-selective peptide can raise the beneficial branch while quieting the other — widening the therapeutic window instead of just lowering the dose.

What is Septagonist?
Septagonist is Panacea Bio Chem's working name for its research direction in signalling-selective peptide design — shaping an agonist so a receptor favours a chosen downstream pathway. It is exploratory work led by Bogdan Dicoias; the specific sequences and methods are proprietary.

Trending in the field

References & further reading

Kenakin T, Christopoulos A. Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nat Rev Drug Discov (2013), PubMed 23411724.
Smith JS, Lefkowitz RJ, Rajagopal S. Biased signalling: from simple switches to allosteric microprocessors. Nat Rev Drug Discov (2018), PubMed 29302067.
Functional selectivity (biased agonism) — overview and β-arrestin signalling. Wikipedia.
Violin JD, Crombie AL, Soergel DG, Lark MW. Biased ligands at G-protein-coupled receptors: promise and progress. Trends Pharmacol Sci (2014), PubMed 24878326.
G protein-coupled receptor — structure and signalling. Wikipedia.