data + articles · 3 listed
newest 2023spec sheet8 rows
alpha-conotoxin txib is a conus textile peptide toxin and one of the most selective alpha6/alpha3beta2beta3 nicotinic antagonists known (rat ic50 ~28 nm, sparing other rat subtypes), with a human alpha6/alpha3beta4 off-target as a species-difference caveat; a clean research probe and drug-design lead for addiction and parkinson's, not a therapeutic in itself.
- one of the cleanest single-subtype alpha6/alpha3beta2beta3 antagonists (rat IC50 ~28 nM, no other rat subtypes hit)
- an attractive lead and template for alpha6-targeted drugs in nicotine addiction and Parkinson's
- documented species-difference (human alpha6/alpha3beta4 off-target) that teaches a real translational caution
- stabilized analogs retain selectivity with improved human-serum stability
Mechanism
alpha-conotoxin txib is a 16-residue toxin from the cone snail conus textile, and it represents the more recent, high-selectivity end of the alpha6 toolkit. according to pubmed, txib acts as a competitive that blocks the rat alpha6/alpha3beta2beta3 receptor with an ic50 around 28 nm while leaving other rat nicotinic subtypes essentially unaffected, an unusually clean single-subtype profile that makes it a favored probe for isolating alpha6* function on terminals (xie et al 2023, doi 10.3390/ijms24108618). that same paper delivered an instructive translational lesson: in human receptors, txib blocks not only alpha6/alpha3beta2beta3 but also alpha6/alpha3beta4 (ic50 around 537 nm), an off-target it does not hit in rat, and the authors mapped the difference to four specific residues (valine-32 and lysine-61 in the alpha6/alpha3 subunit, leucine-107 and valine-115 in the beta4 subunit), underscoring that rodent selectivity data do not always transfer to human receptors. because its selectivity is so attractive, txib is discussed not just as a probe but as a lead for alpha6-targeted therapeutics in nicotine addiction and parkinson's disease, where alpha6beta2* receptors gate the reward-relevant fraction of dopamine release; medicinal-chemistry work has sought to make it more drug-like, and zhang et al identified a modifiable disulfide site ([2][4] cysteine bond) that yields analogs with improved human-serum stability while retaining alpha6* selectivity (doi 10.3390/md19020119). the therapeutic hypothesis it supports is the one laid out for the whole subtype: a selective alpha6beta2* or partial could blunt nicotine reward or protect neurons with fewer off-target effects than broad drugs, because alpha6* receptors are so restricted to catecholaminergic neurons (brunzell et al, doi 10.1111/nyas.12421). the honest bottom line is consistent with the rest of the conotoxin family; txib is a research reagent and a promising design template, not a supplement or approved medicine, valued for giving investigators one of the cleanest available handles on alpha6/alpha3beta2beta3 receptors. note also that the related conus textile toxin txid is a alpha3beta4-selective antagonist, not an alpha6 , and should not be confused with txib.
receptor fingerprint
Rat alpha6/alpha3beta2beta3 (a6*)selective competitive antagonist
Human alpha6/alpha3beta2beta3 antagonist
Human alpha6/alpha3beta4 antagonist (human only; not rat)
Other rat nAChR subtypes (a4b2, a3b4, a7, etc.)no significant block (rat)
Safetyrisks and cautions, not medical advice
Alpha-Conotoxin TxIB is a cone-snail venom peptide studied as a highly selective antagonist of the alpha6/alpha3-beta2-beta3 nicotinic acetylcholine receptor, and it remains purely a research tool with no human safety data. In animal work it blocked nicotine-related conditioned place preference without affecting locomotor activity, which hints at a narrow central action, but this is preclinical behavior data and not a safety evaluation.
As a selective nAChR antagonist it modulates cholinergic signaling, and conotoxins as a class are potent neuroactive venom components, so any theoretical systemic risk to neuromuscular or autonomic function is unquantified in humans. Its disulfide-bridged peptide nature makes it orally inactive and gut-degraded, limiting casual exposure. Honestly stated, no clinical trials, labels, or documented human adverse effects are available, so it should be treated strictly as a reagent.
Subjective profileweighing the evidence above
A research probe, and an excellent one; nobody is meant to take it. Its real value is as a template for alpha6-targeted addiction and Parkinson's drugs, and as a reminder that a rat-clean selectivity profile can pick up an off-target the moment you move to human receptors.
Resources
This entry is here for reference.
Research
- 2014first citedDiverse strategies targeting α7 homomeric and α6β2* heteromeric nicotinic acetylcholine recepto…
- 2023most recentMolecular Determinants of Species Specificity of α-Conotoxin TxIB towards Rat and Human α6/α3β4…
- 1.Molecular Determinants of Species Specificity of α-Conotoxin TxIB towards Rat and Human α6/α3β4 Nicotinic Acetylcholine Receptors.
- 2.Cysteine [2,4] Disulfide Bond as a New Modifiable Site of α-Conotoxin TxIB.
- 3.Diverse strategies targeting α7 homomeric and α6β2* heteromeric nicotinic acetylcholine receptors for smoking cessation.
3 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
what is alpha-conotoxin txib?
it's a 16-amino-acid peptide toxin from the cone snail conus textile, and it's one of the most selective research probes for alpha6-containing nicotinic receptors. according to pubmed, txib is a selective antagonist that blocks the rat alpha6/alpha3beta2beta3 receptor (ic50 around 28 nm) without measurably affecting other rat nicotinic subtypes, which is an unusually clean single-subtype profile (xie et al 2023, doi 10.3390/ijms24108618).
why is txib useful?
because selectivity is the whole game with these tools. the more cleanly a toxin blocks just alpha6* and nothing else, the more confidently you can attribute an experimental effect to alpha6* receptors. txib's near-exclusive rat alpha6/alpha3beta2beta3 profile makes it a favored probe for studying alpha6* receptors on dopamine terminals, which is why it's discussed as a potential lead for both addiction and parkinson's research (zhang et al 2021, doi 10.3390/md19020119).
is it selective in humans too?
mostly, with an important caveat researchers flagged. in humans, txib blocks not only alpha6/alpha3beta2beta3 but also alpha6/alpha3beta4 (ic50 around 537 nm), an off-target it doesn't hit in rats. xie et al traced this species difference to four specific residues and used it as a cautionary example that rodent selectivity data don't always transfer to human receptors (doi 10.3390/ijms24108618). it's a nice reminder to check species when reading nachr pharmacology.
could txib become a drug?
it's being explored as a lead, but the usual peptide caveats apply. its selectivity makes it an attractive starting point for alpha6-targeted therapeutics in nicotine addiction and parkinson's, and chemists have worked on making it more stable; zhang et al found a modifiable disulfide site that yields analogs with better human-serum stability while keeping alpha6* selectivity (doi 10.3390/md19020119). but like all conotoxins, brain delivery and proteolysis are real hurdles, so for now it's primarily a research tool and a design template.
how is it different from mii and pia?
it's the newer, arguably cleanest member of the alpha6 conotoxin toolkit. native mii blocks both alpha3beta2 and alpha6* (its engineered analogs add selectivity); pia was the first to discriminate alpha6 from alpha3; txib blocks essentially only rat alpha6/alpha3beta2beta3. researchers pick among them based on the exact question, species and subtypes involved, and often use several to cross-check receptor identity.
what has it helped show?
txib strengthens the case that alpha6/alpha3beta2beta3 is a discrete, druggable receptor population; its clean block lets researchers isolate that subtype's contribution to dopamine signaling. the ongoing analog and species-difference work (2021-2023) is explicitly aimed at turning that selectivity into a foundation for alpha6-targeted drug discovery in addiction and parkinson's disease.
so what's the honest bottom line?
txib is a highly selective alpha6/alpha3beta2beta3 antagonist and one of the best clean probes for alpha6* biology, especially in rat, with a documented human off-target (alpha6/alpha3beta4) worth remembering. it's a research reagent and a drug-design lead, not a supplement or medicine. it's here as a current, high-selectivity anchor for the alpha6 conotoxin story.