Dolcanatide (SP-333)_Dosage, benefits & legal status
Also known as SP-333
The same atoms as plecanatide, with the first and last amino acids switched to their mirror-image forms to resist digestion. It reached phase 2 for opioid-induced constipation; Bausch Health bought it in 2019 and has reported no development since 2020.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Dolcanatide (SP-333)?
Plain language first. The technical label stays, but it never stands alone.Overview
Opioid painkillers often cause stubborn constipation, and dolcanatide was a version of the constipation drug plecanatide made more resistant to digestion. In a 292-patient phase 2, 3 mg and 6 mg a day raised spontaneous bowel movements by 3.2 and 3.4 a week, against 1.8 on placebo, but the results were only announced in a press release and never published. Synergy dropped this use in 2016, a small cancer-prevention study found it did not activate its target in the rectum, and Bausch Health has reported nothing on it since 2020.
Dolcanatide (SP-333) is a 16-residue guanylate cyclase-C agonist: the sequence of plecanatide (human uroguanylin with glutamate at position 3) with D-asparagine at position 1 and D-leucine at 16, held by Cys4-Cys12 and Cys7-Cys15 disulfides, making it a diastereomer with plecanatide's formula and weight (C65H104N18O26S4, 1681.90). In Synergy Pharmaceuticals' studies it resisted digestive enzymes better than plecanatide in simulated gut fluids and raised cGMP in human T84 colon cells with an EC50 of 2.8 x 10^-7 mol/L against 1.9 x 10^-7 for plecanatide, while almost none reached the blood. It reached a phase 2 in opioid-induced constipation and a rectal phase 1b in ulcerative colitis, and Bausch Health acquired it out of Synergy's bankruptcy on March 6, 2019.
What it's used for
Nothing outside research. It was tested by mouth for opioid-induced constipation and given into the rectum in a small ulcerative colitis study, and it was never approved.
How does Dolcanatide (SP-333) work?
What it does in the body, and where.Dolcanatide copies uroguanylin, a gut hormone that tells the intestinal lining to release fluid, in a form that resists digestion.
- 01Built to last in the gutIts first and last amino acids are mirror-image (D) forms. It resisted protein-cutting enzymes in simulated stomach and intestinal fluids better than plecanatide, and it stayed stable in simulated intestinal fluid for up to 24 hours.
- 02Switching on the receptorIt binds guanylate cyclase-C on the gut-facing surface of lining cells and raises cyclic GMP inside them, about as potently as plecanatide in human colon cells (EC50 2.8 x 10^-7 against 1.9 x 10^-7 mol/L).
- 03Fluid into the bowelCyclic GMP drives chloride and bicarbonate secretion, water follows, and stool softens and moves faster. Almost none reaches the blood: levels were below 1 ng/mL at doses under 10 mg. In the NCI study, 27 mg by mouth did not raise cGMP in the distal rectum, so the active peptide may not reach the lower bowel.
A schematic of the compound's mechanism, not a diagnostic image.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
Opioid-induced constipation (phase 2)
Investigational- Human trial292 enrolled, 4 weeks: spontaneous bowel movements a week up 3.2 on 3 mg (p=0.009) and 3.4 on 6 mg (p=0.005) against 1.8 on placebo; complete ones up 2.54 and 2.39 against 1.36.
- No dataAnnounced only as preliminary results in a company release; never published, and no results posted on ClinicalTrials.gov.
- RegulatorySynergy said in February 2016 it had no plans to continue development in this use.
Ulcerative colitis (phase 1b, rectal)
Early research- human-early28 patients with mild to moderate ulcerative colitis got 6 mg in saline into the rectum each evening or placebo for 28 days; Synergy reported clear signals of improvement but released no scores or p-values.
Colorectal cancer prevention (NCI phase 1)
tested-and-failed- Human trial27 healthy adults randomized (24 evaluable) to 27 mg a day or placebo for 7 days: rectal epithelial cGMP changed by -0.42 ± 0.43 against -0.22 ± 0.29 pmol/mg (p=0.15).
- Human trialThe published paper concluded its stability and persistence are inadequate to regulate GUCY2C across the colorectum, and that a version released in the colon would be needed.
Healthy-volunteer studies (phase 1)
Investigational- human-earlySingle doses of 0.1 to 60 mg in 64 people (48 active): diarrhea was dose-related from 1 mg, and blood levels were below 1 ng/mL in most.
- human-earlyDaily doses for 14 days (7 days at 60 mg): 30 mg was the maximum tolerated dose, and 60 mg caused 2 episodes of fecal incontinence or soiling among 6 people.
- No dataNeither study has been published as a full paper.
Lab and animal studies
Research only- Lab studyRaised cGMP in human T84 colon cells with an EC50 of 2.8 x 10^-7 mol/L, against 1.9 x 10^-7 for plecanatide.
- Animal studyOral dosing reduced chemically induced (DSS) colitis in mice, with most doses lowering tissue damage scores about as much as 5-ASA; the paper's spontaneous-colitis test in T-cell receptor alpha knockout mice used plecanatide, not dolcanatide.
It is often described as having a published phase 1 trial as its evidence; the largest study is the 292-patient phase 2 in opioid-induced constipation (NCT01983306). It met its main endpoint at 3 mg (p=0.009) and 6 mg (p=0.005) but was never published. It is also reported as an oral peptide across the board, yet the ulcerative colitis phase 1b gave 6 mg into the rectum. The NCI result is reported correctly as no rise in rectal cGMP (-0.42 against -0.22 pmol/mg, p=0.15, 13 against 11 evaluable), but it was a 7-day study in healthy volunteers, not a cancer outcome trial. Calling it a uroguanylin analog is loose: it is plecanatide's exact sequence with D-forms at positions 1 and 16, a diastereomer with the same formula and weight. It is sometimes credited to Bausch Health, but Bausch only bought it in 2019; Synergy or the NCI ran every known human study. The phase 2 size appears as 289 in Synergy's release and 292 in the registry. SP-303 is sometimes listed as an alias; GSRS lists SP-333 as its only code.
The published record
Papers and trials about Dolcanatide (SP-333)
7 papers tagged human · 3 not reviews or lab · 1 clinical trial publications
3 registered trials · 1 with posted results
Furthest stage reached: Phase 2, completed, no results posted
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about Dolcanatide (SP-333)
Evidence
Investigational
Category
Healing and recovery
Common vial
Varies
Half-life
Not established
How much, and do you cycle it?
The range, and whether you take breaks.3 or 6 mg once daily (phase 2 trial), once daily (phase 2 trial). Daily for 4 weeks in the phase 2; longer use not studied Trial dose
The longest trials ran 28 days (the phase 2 and the rectal colitis study), and development stalled after that, so there is no established schedule.
Not establishedNo figure
Blood levels were below the 1.0 ng/mL limit of measurement in most people, so no half-life could be calculated. In the single-dose study only the 60 mg group had measurable levels at several time points, peaking at 0.50 hours; in the 14-day study nothing was measurable below 10 mg, levels were measurable in 8 of 31 at 10 mg or more, and none after 2.0 hours. It acts inside the gut; the protocol estimated that at most 10 to 20% of an oral dose stays active in the distal colon, an estimate rather than a measurement.
Source: NCT03300570 protocol, background on Synergy's phase 1 studies
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What does it cost?
Typical dose and cost, in plain numbers.Dolcanatide (SP-333) is not injected
It is taken by mouth (oral). Taken by mouth as a tablet once a day for 4 weeks in the opioid-induced constipation phase 2, at 1, 3 or 6 mg against placebo; 3 and 6 mg met the main endpoint. Healthy-volunteer studies gave single doses of 0.1 to 60 mg and daily doses of 0.3 to 30 mg for 14 days (60 mg for 7 days), and 30 mg was the maximum tolerated dose. The ulcerative colitis phase 1b gave 6 mg dissolved in saline into the rectum each evening for 28 days, and the NCI study gave 27 mg a day as three 9 mg capsules for 7 days. No kidney or liver data have been reported. It was never approved and no product exists, so the calculator starts with an empty dose field.
How do you store it?
Before mixing, and after.Room temperature. Cool, dry, out of light.
Dolcanatide (SP-333) is taken as a pill or capsule. Keep it in its original container at room temperature, away from heat, humidity, and direct sun. No fridge or mixing needed. Check the expiration date on the bottle.
What are the side effects and cautions?
Known cautions and warnings for this compound.Solubility, computed: 31% charged residues, 56% hydrophobic. Water usually sufficient.
A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.
Who should avoid it
- Not studied in children: the constipation phase 2 and the NCI study enrolled adults only
- Not studied in people taking opioids for cancer pain: the phase 2 enrolled adults on opioids for chronic non-cancer pain for at least 3 months
- Not studied for longer than 4 weeks: the longest trials ran 28 days
- Use outside a trial: it was never approved, and no medicinal product exists
Stop and get help
- Severe or persistent diarrhea, or signs of dehydration such as dizziness or passing very little urine: diarrhea led 2 people on 6 mg to withdraw from the phase 2
- Loss of bowel control: fecal incontinence or soiling made 60 mg a day intolerable in healthy volunteers
Common effects
- Diarrhea in 4.0%, 5.4% and 9.7% on 1, 3 and 6 mg against 0% on placebo over the 4-week phase 2
- Serious adverse events in 0, 1 and 1 people on 1, 3 and 6 mg against 2 on placebo; 2 people on 6 mg withdrew for diarrhea
- In the single-dose healthy-volunteer study, diarrhea was dose-related from 1 mg and affected at least 50% at 10 mg and above
- In the 14-day study, diarrhea affected more than 65% at every dose and urgency was also reported, all mild to moderate, with no serious events or withdrawals; 60 mg caused 2 episodes of fecal incontinence or soiling among 6 people. In the NCI study, 11 of 14 people on 27 mg a day had diarrhea against 0 of 13 on placebo; 1 had severe (grade 3 or higher) diarrhea and 1 withdrew for a side effect
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Dolcanatide (SP-333) approved?
And where the numbers on this page come from.No. Dolcanatide (SP-333) was never approved, and no development has been reported in recent years. There is no legal route to obtain it as a medicine.
- Approval statusInvestigational
- RouteBy mouth (oral)
- Checked21 October 2026
- DoseFrom published clinical trials. Not approved by a regulator for this dose.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesFDA GSRS substance record, dolcanatide (UNII WU977T914K)KEGG D11233, dolcanatideShailubhai K et al., World Journal of Gastrointestinal Pharmacology and Therapeutics 2015;6:213-222Synergy Pharmaceuticals, Form 8-K exhibit 99.1 (November 19, 2014)ClinicalTrials.gov, NCT01983306Synergy Pharmaceuticals, Form 8-K exhibit 99.1 (January 11, 2016)US patent application 2020/0316164 (Justia)Weinberg DS et al., Cancer Biology and Therapy 2021;22:544-553ClinicalTrials.gov, NCT03300570NCT03300570 protocol and statistical analysis planSynergy Pharmaceuticals, Form 10-K filed February 25, 2016Bausch Health, acquisition of Synergy assets completed (March 6, 2019)Bausch Health, investor presentation (Form 8-K, January 13, 2020)Bausch Health, annual meeting presentation (Form 8-K, April 28, 2020)
What has happened recently
Never approved anywhere, and no orphan, fast track or breakthrough designation was found. Synergy Pharmaceuticals announced the start of phase 1 dosing in October 2012; its single- and multiple-dose studies in healthy volunteers set the maximum tolerated dose at 30 mg. The phase 2 in opioid-induced constipation (NCT01983306) ran from November 2013 to April 2015, with preliminary positive results announced on November 19, 2014; Synergy's 10-K filed February 25, 2016, said it had no plans to continue development in that use. A 28-patient ulcerative colitis phase 1b, given into the rectum, was announced on January 11, 2016, and by its 10-K filed March 1, 2018, Synergy was seeking business-development options for that use. The National Cancer Institute ran a phase 1 prevention study (NCT03300570) under IND 139462 from July 27, 2018, to May 17, 2021, with Synergy supplying the drug. Synergy announced Chapter 11 proceedings on December 12, 2018; the bankruptcy court approved the sale on March 1, 2019, and Bausch Health closed it on March 6, 2019, for about $195 million in cash plus certain assumed liabilities, adding dolcanatide to its early pipeline. Bausch listed it under pipeline expansion on January 13, 2020, and its last mention found, on April 28, 2020, refers to it only as part of that acquisition; no discontinuation has been announced. AdisInsight lists the constipation program as discontinued and, citing Salix's September 2019 pipeline, an oral phase 2 in ulcerative colitis; no such trial or result has been reported, and no Bausch SEC filing mentions dolcanatide after April 28, 2020. US composition-of-matter patents expire in 2028.
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What else is like Dolcanatide (SP-333)?
Others in Healing and recovery, side by side.If you're weighing Dolcanatide (SP-333), it's worth reading Serelaxin (RLX030), BPC-157, and TB-500 / Thymosin Beta-4 in the same class.
The same atoms as plecanatide, with the first and last amino acids switched to their mirror-image forms to resist digestion. It reached phase 2 for opioid-induced constipation; Bausch Health bought it in 2019 and has reported no development since 2020.
- Dose
- 3 or 6 mg once daily (phase 2 trial)
- How often
- Once daily (phase 2 trial)
Recombinant human relaxin-2, a two-chain hormone that relaxes arteries, given as a 48-hour drip in acute heart failure. In RELAX-AHF-2 cardiovascular deaths were 8.7% against 8.9% on placebo, and Novartis ended development in 2017.
- Dose
- 30 mcg/kg per day by continuous infusion for 48 hours (phase 3 trials)
- How often
- Once, as a single 48-hour infusion
A popular healing peptide for injuries, gut, and joint or tendon pain.
- Dose
- 0.25 up to 0.5 mg per dose (start low, increase slowly)
- How often
- 1-2x daily
A recovery peptide for healing muscle and tendon, often paired with BPC-157.
- Dose
- 2 up to 2.5 mg per injection (start low, increase slowly)
- How often
- Twice a week
Guides for this compound
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- FDA GSRS substance record, dolcanatide (UNII WU977T914K)(2026)CAS 1092457-65-2; sequence with D-asparagine 1 and D-leucine 16; disulfides 4-12 and 7-15; INN and USAN; code SP-333.
- KEGG D11233, dolcanatide(2026)C65H104N18O26S4, MW 1681.90, the same as plecanatide (KEGG D09948).
- Shailubhai K et al., World Journal of Gastrointestinal Pharmacology and Therapeutics 2015;6:213-222(2015)D-Asn1 and D-Leu16 replace plecanatide's L forms; EC50 2.8 x 10^-7 against 1.9 x 10^-7 mol/L in T84 cells; more resistant to digestion; less colitis in mice.
- Synergy Pharmaceuticals, Form 8-K exhibit 99.1 (November 19, 2014)(2014)Preliminary phase 2 results: weekly spontaneous bowel movements up 3.2 (3 mg, p=0.009) and 3.4 (6 mg, p=0.005) against 1.8 on placebo; diarrhea 4.0 to 9.7%.
- ClinicalTrials.gov, NCT01983306(2021)Randomized phase 2, 292 enrolled; 1, 3 or 6 mg daily for 4 weeks; November 2013 to April 2015; no results posted; sponsor now Bausch Health Americas.
- Synergy Pharmaceuticals, Form 8-K exhibit 99.1 (January 11, 2016)(2016)Ulcerative colitis phase 1b in 28 patients: clear signals of improvement against placebo, with no numbers.
- US patent application 2020/0316164 (Justia)(2020)The colitis phase 1b gave 6 mg into the rectum each evening for 28 days; sequence SEQ ID NO: 9.
- Weinberg DS et al., Cancer Biology and Therapy 2021;22:544-553(2021)27 mg a day for 7 days did not activate GUCY2C, measured as cGMP, in the distal rectum of healthy volunteers.
- ClinicalTrials.gov, NCT03300570(2021)NCI phase 1, 27 randomized and 24 evaluable: rectal cGMP change -0.42 against -0.22 pmol/mg (p=0.15).
- NCT03300570 protocol and statistical analysis plan(2018)Phase 1 doses; plasma levels mostly below 1 ng/mL; maximum tolerated dose 30 mg; diarrhea rates; IND 139462; 9 mg capsules.
- Synergy Pharmaceuticals, Form 10-K filed February 25, 2016(2016)No plans to continue dolcanatide development in opioid-induced constipation; evaluating the colitis program; patents expiring 2028.
- Bausch Health, acquisition of Synergy assets completed (March 6, 2019)(2019)About $195 million in cash plus certain assumed liabilities; dolcanatide added to the early pipeline.
- Bausch Health, investor presentation (Form 8-K, January 13, 2020)(2020)Dolcanatide listed under R&D pipeline expansion, not among late-stage programs.
- Bausch Health, annual meeting presentation (Form 8-K, April 28, 2020)(2020)Dolcanatide mentioned only as part of the 2019 acquisition; the latest Bausch mention found.
Beyond these, 10 records are indexed. Browse the records