Tiplimotide
A deliberately altered piece of myelin basic protein, meant to steer the T cells that attack myelin in multiple sclerosis toward a harmless response
Tiplimotide (NBI-5788) is a 17-amino-acid peptide copied from the region 83 to 99 of myelin basic protein, a target of the immune attack in multiple sclerosis, with several residues swapped and a D-alanine at its start. The idea, called an altered peptide ligand, was that T cells recognising the native myelin peptide would meet the altered one and switch to an anti-inflammatory 'T-helper 2' pattern. In patients given it under the skin weekly for four weeks around 2000, it did expand T cells with that pattern. Development continued into an intravenous phase 2 programme in the mid-2000s, but it was never approved.
Used in human trials: 5, 10 or 20 mg, Once weekly, Subcutaneous (Relapsing MS, immune-response study) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
In multiple sclerosis the immune system attacks myelin, the insulating sheath around nerve fibres in the brain and spinal cord. One of the pieces of myelin that patients' T cells react to most strongly is a stretch of myelin basic protein running from amino acid 83 to 99. In the 1990s immunologists found that changing a few amino acids in such a target peptide could produce an 'altered peptide ligand': T cells still recognise it, but instead of switching on fully they may respond weakly or switch to a different, less inflammatory programme. Tiplimotide is an altered peptide ligand of myelin basic protein 83-99, developed under the code NBI-5788.
Its sequence, as PubChem records it, keeps most of the native region but changes several residues and begins with a D-alanine, the mirror-image form of the amino acid, which slows breakdown. A 1997 review of antigen-specific therapies for multiple sclerosis listed it among three intravenous myelin-antigen products then entering phase 1 trials, beside a recombinant myelin fusion protein and a soluble HLA-DR2 complex.
The one study of the drug by name in people that we found measured immune responses in patients who had received it at 5, 10 or 20 mg under the skin once a week for four weeks. Compared with untreated patients, those treated had a far higher frequency of T cells that responded to the altered peptide (about 36% against 6%), while responses to whole myelin basic protein were unchanged. T-cell lines from treated patients more often also recognised the native 83-99 peptide and more often produced T-helper 2-like cytokines. The authors read this as the intended shift toward an anti-inflammatory response, while noting how much patients differed from one another.
Development did not stop there. A 2005 drug profile describes the developer working on it as a potential intravenous treatment, with enrolment in phase 2 trials complete by April 2005 and results expected in 2006. We found no published results of those trials, no later trial records and no approval: Drugs@FDA and the EMA list hold none, and ChEMBL records phase 2 as its highest stage. Two other papers on an altered myelin basic protein 83-99 peptide from that period, listed under References, do not name the drug in their abstracts, so their findings are not attributed to tiplimotide here.
Tiplimotide is a historical investigational drug, not a treatment and not a product. The peptide-based multiple sclerosis drug that did reach patients is glatiramer acetate, which has its own entry.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Mechanism of Action
Tiplimotide is a modified copy of a myelin basic protein fragment that T cells in multiple sclerosis recognise. By changing contact residues it was meant to engage those T cells without fully activating them, steering them toward a T-helper 2 response that cross-reacts with the native peptide.
Altered peptide ligand
Built from the immunodominant 83-99 region of myelin basic protein with amino acid substitutions, so that myelin-reactive T cells still bind it but respond differently.
Shift to T-helper 2
In treated patients, T-cell lines reacting to the drug more often secreted T-helper 2-like cytokines than lines from untreated patients.
Cross-reaction with native myelin peptide
Drug-reactive T cells from treated patients more often also recognised native myelin basic protein 83-99, the basis for hoping they would damp inflammation where myelin is attacked.
Published Research
These are the studies of tiplimotide (NBI-5788) we found and read from their PubMed abstracts on October 30, 2026: the immune study in treated patients and two reviews that name it. Two further trial reports of an altered myelin basic protein peptide, which do not name the drug in their abstracts, are listed under References only.
A T-helper 2-like response in treated MS patients
Patients who had received 5, 10 or 20 mg under the skin weekly for four weeks had a mean frequency of drug-responsive T cells of 35.8%, against 6.2% in seven untreated patients, with no difference in responses to whole myelin basic protein. Their drug-reactive T-cell lines more often cross-reacted with native peptide 83-99 and more often made T-helper 2-like cytokines; responses varied widely between patients.
Drug profile: an intravenous phase 2 programme
A 2005 profile describes NBI-5788 as an analogue of an immunodominant myelin basic protein epitope being developed for intravenous treatment of multiple sclerosis, with phase 2 enrolment complete by April 2005 and results expected in early 2006.
Antigen-specific MS therapies in the clinic, 1997
A review of antigen-specific approaches to multiple sclerosis lists NBI-5788, an altered peptide ligand of an immunodominant myelin basic protein T-cell epitope, as one of three intravenous myelin-antigen products entering phase 1 trials that year.
Dosing Data
Tiplimotide has no approved label. The row below is the schedule given to the patients in its one human study that names the drug; it is a study amount, not a recommendation.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
The abstracts that name tiplimotide report immune measurements, not side effects.
Contraindications & Cautions
No approved label exists, so there are no official contraindications.
Legal Status
Tiplimotide is not approved in any jurisdiction checked.
Frequently Asked Questions
?What is tiplimotide?
NBI-5788, a 17-amino-acid peptide copied from myelin basic protein 83-99 with deliberate substitutions, tested in multiple sclerosis around 2000 as an 'altered peptide ligand'.
?What was it supposed to do?
Engage the T cells that attack myelin without fully activating them, shifting them to a T-helper 2 pattern that might calm inflammation where they meet myelin.
?Did it work?
It produced the intended immune shift in treated patients' blood cells. No published clinical results of its later phase 2 trials were found, and it was never approved.
?Is it related to glatiramer acetate?
Both are peptide approaches to multiple sclerosis, but glatiramer acetate is a random mixture of four amino acids, while tiplimotide is one defined sequence copied from myelin basic protein.
References
- [other] PubChem CID 25080873, Tiplimotide: formula C87H142N24O21, molecular weight 1860.2. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/25080873
- [other] ChEMBL CHEMBL2108869, tiplimotide (synonyms include NBI-5788): maximum clinical phase 2 in the ChEMBL molecule record, read October 2, 2026 (the Registry's ChEMBL harvest). https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2108869/
- [pubmed] Crowe PD, et al. "NBI-5788, an altered MBP83-99 peptide, induces a T-helper 2-like immune response in multiple sclerosis patients." Ann Neurol, 2000;48(5):758-65. PMID: 11079539.
- [pubmed] Darlington CL. "NBI-5788 Neurocrine." Curr Opin Investig Drugs, 2005;6(7):747-51. PMID: 16044672.
- [pubmed] Spack EG. "Antigen-specific therapies for the treatment of multiple sclerosis: a clinical trial update." Expert Opin Investig Drugs, 1997;6(11):1715-27. PMID: 15989576.
- [pubmed] Kappos L, et al. "Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group." Nat Med, 2000;6(10):1176-82. PMID: 11017151.
- [pubmed] Kim HJ, et al. "Persistence of immune responses to altered and native myelin antigens in patients with multiple sclerosis treated with altered peptide ligand." Clin Immunol, 2002;104(2):105-14. PMID: 12165271.
Sources & Citations
Studies were read from their PubMed records on October 30, 2026. Regulatory status comes from Drugs@FDA and the EMA medicines list and trial listings from ClinicalTrials.gov (searched October 28, 2026); sequence, formula and weight are PubChem's and the highest phase is ChEMBL's. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.