Adenosine Bench
KW-6356 next to caffeine and istradefylline, with the unpublished trials named
Overview
KW-6356 (sipagladenant) is the discontinued Kyowa Kirin A2A antagonist that gets sold online as a cleaner caffeine. this bench puts it next to caffeine and istradefylline and says what was measured, what was buried, and what was never tested.
Read this first
KW-6356 is research use only. BHG Labs sells it as a capsule research compound with a third-party COA on every lot; that certificate says what is in the capsule, not what it does in a healthy person, because no study has ever looked. it was built for Parkinson's disease, the company that made it stopped in 2022, and the trials that would answer the questions people actually ask (heart rhythm, caffeine, CYP3A4 drugs, side-effect rates) were completed and never published. nothing on this page is an amount or a schedule.
The bench: 3 compounds
roles and evidence, not amounts. this page does not publish doses or schedules for research compounds.
1KW-6356small human trials
read the guidethe subject. a non-xanthine adenosine A2A antagonist and inverse agonist with sub-nanomolar affinity (Ki about 0.12 nM), insurmountable binding, and a human half-life of 18 to 43 hours. Kyowa Kirin stopped development in July 2022 for regulatory and timeline reasons, not for a safety or efficacy failure.
evidence: eight completed trials, all phase 1 or 2, all in Parkinson's disease or healthy-volunteer pharmacokinetics. the 12-week monotherapy trial (168 treated) moved MDS-UPDRS Part III more than placebo. the 503-patient levodopa-adjunct trial met its primary endpoint but exists only as a 2022 conference abstract and a press release. no study measured focus, mood, motivation or memory in anyone.
watch for: the thorough QT study (128 subjects), the caffeine and CYP3A4 interaction studies and the full adverse-event table were completed and never published. the longest healthy-volunteer exposure is 14 days. one vendor sells it as 'Metabolite 6', which is the name of its active metabolite, not the parent compound.
2Caffeinehuman trials
read the guidethe mechanistic reference. a low-affinity antagonist at all four adenosine receptors, cleared in 4 to 5 hours through CYP1A2. everyone reading this already has a calibrated feel for it, which is why it belongs on the page.
evidence: decades of human data on alertness and performance. none of it involves KW-6356.
watch for: KW-6356 hits the same receptor at sub-nanomolar instead of micromolar concentration and stays in the body for days (half-life 18 to 43 hours). no human study has run the two together on any effect endpoint; the one trial that gave both used caffeine as a CYP1A2 probe (NCT03970798) and never reported the result.
3Istradefyllinehuman trials
the clinical reference. the approved sibling from the same company (Nourianz, FDA 2019), a surmountable neutral antagonist with roughly one hundredth the A2A affinity. it is the approved one, so it is the one with a prescribing label to read.
evidence: approved for OFF episodes in Parkinson's patients on levodopa. the label lists dyskinesia (15 to 17% versus 8% on placebo), dizziness, constipation, nausea, hallucination and insomnia as the common adverse reactions; strong CYP3A4 inhibitors raise its exposure about 2.5-fold and smoking lowers it.
watch for: the label's 15 to 17% dyskinesia rate and the pivotal trial's 'no increase in troublesome dyskinesia' are both true; they count different things.
Form
capsules, as sold
Human data
eight completed Kyowa Kirin trials for KW-6356, three of them published; decades for caffeine; a full label for istradefylline
BHG Labs carries
1 of 3
Level
advanced
Why these together
caffeine and istradefylline are on the page as reference points, not as a stack. caffeine is what your body already knows about adenosine blockade, so it calibrates every claim about KW-6356. istradefylline is the approved sibling with a real label, so it supplies the class-level numbers that KW-6356's own unpublished trials cannot. KW-6356 is the only one of the three BHG Labs sells.
Overlap
all three block the A2A receptor, and at A2A the overlap is complete: adding caffeine to KW-6356 is adding a weak, short antagonist on top of a strong, long one that is already bound. the only study that gave both compounds together used caffeine as a CYP1A2 probe (NCT03970798) and its result was never released. in mice, a different selective A2A antagonist cross-sensitised animals to caffeine and raised striatal dopamine; that is a class signal from another molecule, not KW-6356 data.
Conflicts
two A2A antagonists together (KW-6356 with istradefylline, or with theacrine): duplication, and the phase 2b excluded prior A2A antagonist use. strong CYP3A4 inhibitors and inducers (clarithromycin, azoles, ritonavir, grapefruit, rifampicin, carbamazepine, St John's wort): the sponsor ran the interaction study, kept these drugs out of its trials, and never published the numbers, so treat them as live. levodopa: KW-6356 potentiated it in marmosets, and 21 days together with low-dose levodopa increased dyskinesia. dopamine antagonists (antipsychotics, metoclopramide, tetrabenazine): excluded from the trials. resting pulse over 100 or blood pressure over 140/90: excluded from the trials.
What the evidence actually is
KW-6356: one published phase 2a in Parkinson's (168 treated, 12 weeks, a modest MDS-UPDRS III gain over placebo), one unpublished phase 2b (503 patients, primary endpoint met, conference abstract only), phase 1 pharmacokinetics in healthy volunteers, two marmoset papers, six PubMed records in total. caffeine: decades of human trials. istradefylline: an approved label with dyskinesia, CYP3A4 and smoking numbers. nobody has measured a cognitive, mood or motivation endpoint for KW-6356 in any species.
What people report
vendor pages promise cleaner focus and no tolerance. no trial measured either, and the closest animal work (a different A2A antagonist in mice) found sensitisation and cross-sensitisation with caffeine, not tolerance-free stability.
Who It's For
people who keep seeing KW-6356 sold as a caffeine upgrade and want the actual record before deciding anything
What to Track
resting pulse, sleep, headache days, caffeine intake
Sourced at BHG Labs
Ownership disclosure: BHG Labs and BodyHackGuide are commonly owned. When you buy from BHG Labs, the team behind this site benefits, so read the evidence sections above with that in mind. Third-party COA on every lot. Research use only. Code BHG20 takes 20% off at checkout, and the store links below apply it for you.
caffeine and istradefylline are reference points. BHG Labs sells neither, and istradefylline is a prescription drug.
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