Peptide education
Thymogen
Thymogen is a two-amino-acid synthetic peptide, glutamic acid joined to tryptophan, usually written alpha-glutamyl-tryptophan or Glu-Trp. Russian documents sell it as Timogen in nasal spray, injection, cream, and gastric gel forms, while U.S. oncology databases know the disodium salt as oglufanide or IM-862. It is one of the few bioregulator peptides with actual controlled human trials behind it. Those trials are narrow, and dosing across the product forms runs from 25 micrograms per spray to 20 mg three times daily, so "thymogen" only means something once the form is named.
Thymogen has real labels and two controlled human positives: a gastritis program and a perioperative trial. The broad immune, anti-aging, and cancer claims online ignore how narrow those wins are, how decisively the IM-862 oncology program failed, and how far apart microgram sprays, gastric gels, and milligram oncology drops sit.
Overview
Quick answer
The Thymogen name appears across several product contexts: microgram-scale Russian nasal spray and intramuscular products, a topical cream, an oral gastric gel family, milligram-scale oncology intranasal IM-862 studies, 10 mg to 20 mg research vials, and blended oral products sold as "Thymogen Alpha-1." Those are different products, routes, amounts, and quality issues.
What is Thymogen?
Alpha-glutamyl-tryptophan: a synthetic Glu-Trp dipeptide from the Russian thymic-peptide research lineage. In older oncology development material the same substance family appears as oglufanide disodium or IM-862.
What do people use it for or talk about?
Official Russian materials cover immune and infection-adjacent uses, a dermatology cream, and a gastric gel. The human studies on this page cover perioperative immune correction, chronic atrophic H. pylori gastritis, AIDS-related Kaposi sarcoma, and metastatic kidney cancer. Online sellers stretch the name across immune support, anti-aging, COVID-era claims, and cancer control.
What routes, amounts, and durations show up?
Russian labels work in micrograms: 25 per nasal spray, or 100 micrograms per mL in intramuscular solution, in courses of 3 to 10 days. The perioperative trial used 0.1 mg intranasally for 7 to 10 days before surgery. The gastritis program used an oral gel twice daily for 28 days after H. pylori eradication. The IM-862 oncology studies ran intranasal milligram regimens up to 20 mg three times daily in 8-week cycles.
Is it a broad immune booster?
No. The labels and studies behind it are condition-specific: one perioperative trial, one gastritis program, regional infection labeling. Nobody has shown that thymogen improves immunity in healthy people, and nothing in the cited record measures anti-aging outcomes at all.
Why are Thymogen products not interchangeable?
Because the dose scales differ by orders of magnitude and the biology changes with the route. A 25-microgram spray, a 100-microgram injection, an oral gastric gel, 5 to 20 mg oncology drops, and a 10 mg gray-market vial are different exposures aimed at different problems. A single "Thymogen protocol" that blends them is meaningless.
Reported practice
Commonly reported protocol
No established community protocol. Community-reported patterns, not verified by controlled human trials and not a use recommendation. Full use-pattern detail
Evidence
Evidence snapshot
A clustered Russian placebo-controlled program reported acid-function, histology, and inflammatory-cell findings after 28 days of oral alpha-glutamyl-tryptophan gel following H. pylori eradication.
An elderly abdominal-cancer surgery study reported fewer postoperative complications after short-course preoperative intranasal thymogen, but it is older, single-country evidence with limited visible replication.
IM-862 produced early AIDS-related Kaposi sarcoma interest, but later placebo-controlled AIDS-KS work and a metastatic renal cell carcinoma study do not support cancer-treatment claims.
Russian product documents describe nasal spray, intramuscular solution, cream, and gastric gel uses. That shows how regional products are framed; it does not amount to FDA approval or broad international efficacy.
Vendor pages and supplement products blur free acid, sodium or disodium salt, research vials, official products, and blended "Thymogen Alpha-1" products. One vendor formula example mismatched reference chemistry.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Anecdotal evidence | Verdict |
|---|---|---|---|---|
| Thymogen is alpha-glutamyl-tryptophan. | Human studies cannot settle chemical identity by themselves, but Russian label documents and drug databases consistently connect Thymogen with alpha-glutamyl-tryptophan, while oncology material connects related development naming to oglufanide disodium or IM-862. | The molecule is a Glu-Trp dipeptide. Some mechanistic papers discuss immune-cell signaling, inflammatory cytokines, endothelial-cell markers, and promoter-binding hypotheses for short peptides. | Online sellers use several names, including Thymogen, Timogen, Thymagen, oglufanide, and Thymogen Alpha-1. That naming spread makes identity verification unusually important. | Alpha-glutamyl-tryptophan is the main identity when the material is talking about that dipeptide. Products carrying the name may still differ by salt form, formulation, or blend. |
| Thymogen supports immune function. | Russian labels and older clinical studies discuss immunomodulatory use, immune-marker changes, infection-related settings, and short courses. The better-supported human findings remain condition-specific, such as perioperative use and chronic atrophic gastritis endpoints. | Cell-model work describes effects on inflammatory signaling, TNF and IL-6 expression in THP-1 systems, adhesion to activated endothelial cells, IL-1alpha production, and ICAM-1 surface expression. | Vendor and wellness pages often turn "immunomodulatory" into broad immune boosting, seasonal illness, anti-aging, or recovery language. | The human findings come from specific products and settings, including perioperative use and chronic atrophic gastritis studies. They do not show that thymogen broadly improves immunity in healthy people. |
| Thymogen helps chronic atrophic gastritis. | The clearest human cluster is the Russian chronic atrophic H. pylori gastritis program. It used oral alpha-glutamyl-tryptophan gel twice daily for 28 days after eradication therapy and reported pH or acid-function, histology, gland-density, and inflammatory-cell outcomes. | A local gastric formulation is a different biological question from systemic intranasal or intramuscular exposure. The gastric papers and formulation descriptions make route-specific interpretation important. | This is mainly a Russian product and clinical-literature claim, not an internet anecdote. | This is a narrow human finding, not broad evidence for gut healing, systemic immunity, or anti-aging claims. |
| Thymogen prevents colds or treats respiratory infections. | Russian nasal spray labeling includes prophylaxis and adjunctive treatment language for acute viral respiratory infections, and a recent company observational ARVI report is mentioned. No convincing modern, independent randomized respiratory-outcomes literature is cited here. | Immune-cell signaling work can explain why respiratory claims exist, but it is not prevention or treatment evidence for broad populations. | Online immune-support marketing often leans on cold, flu, COVID-era, and seasonal-illness language. | The evidence consists of regional-label and weak observational context and is too weak to support a broad respiratory-treatment claim. |
| Thymogen is an anti-cancer peptide. | The oncology record is mixed and mostly limits cancer claims. An early AIDS-related Kaposi sarcoma study reported activity with IM-862 nasal drops, but a later placebo-controlled AIDS-KS study found no significant response-rate advantage. A metastatic renal cell carcinoma phase 2 study reported no objective responses. | Immune and angiogenesis-related hypotheses put IM-862 into oncology research, but the cited studies did not show dependable cancer efficacy. | Cancer-control claims can appear in peptide marketing because the IM-862 history sounds more impressive when the negative and nonconfirmatory studies are left out. | Thymogen is not supported as a cancer therapy. The oncology history is a warning against cancer-treatment marketing, not evidence of benefit. |
| Thymogen is an anti-aging or longevity peptide. | The human evidence here does not make thymogen a longevity, healthy-aging, performance, or recovery drug in healthy people. | Short-peptide gene-expression theories, thymic-peptide history, and some preclinical aging or immune biology explain why the topic is studied. A human longevity effect has not been shown. | Bioregulator and gray-market discussions often place thymogen near anti-aging, immune rejuvenation, and thymosin alpha-1 comparison claims. | No study in this source set measured lifespan, frailty, or healthy-aging outcomes in people. |
| Research vials or blended supplements are equivalent to official Thymogen products. | Formal labels and studies describe specific products and regimens. They leave 10 mg or 20 mg research vials, clinic reconstitution products, and oral blends sold under similar names unconfirmed. | This is mainly a product-quality issue: salt form, molecular weight, formulation, potency, impurities, sterility, endotoxin, stability, and route-specific exposure. | One vendor example lists formula and molecular-weight information that mismatches reference free-acid data, while another sells a "Thymogen Alpha-1" blend rather than standalone thymogen. | Misleading as a shortcut. Product identity and batch documentation have to be checked separately from the molecule's formal literature. |
Bottom line
Main takeaway
Thymogen is a defined short peptide with genuine Russian product registrations and a couple of controlled human studies. The internet version, a universal immune and anti-aging booster, is not what the labels or the trials describe.
Sort products by form before comparing anything: nasal spray, intramuscular ampoule, gastric gel, oncology IM-862 drops, research vials, and "Thymogen Alpha-1" blends each carry their own dose scale, evidence, and quality burden. One vendor's stated formula did not even match the reference chemistry.
The anchors are the Russian label documents, the 2011 perioperative RCT, the 2022 to 2023 gastritis papers, the IM-862 phase 2 and phase 3 oncology studies, and the vendor examples showing identity drift. Together they show narrow positives, a failed cancer program, and a messy market.
Identity
What it is
Thymogen is alpha-glutamyl-tryptophan, a synthetic dipeptide of glutamic acid and tryptophan. It comes out of the same Russian thymic-peptide lineage as thymalin, but unlike thymalin it is one defined molecule rather than an organ extract.
The name spans an unusual dose range. Russian labels work in micrograms (25 per nasal spray, 100 per mL for injection), the gastritis program used an oral gel, and the IM-862 oncology studies dosed in milligrams intranasally. Form and route are not footnotes here: they decide which evidence, if any, applies to a given product.
The controlled human record has two positives and one clear failure. A placebo-controlled Russian gastritis program reported acid-function and histology improvements after 28 days of oral gel, and an older double-blind trial reported fewer postoperative complications in elderly abdominal-cancer surgery patients. The IM-862 oncology program went the other way: early AIDS-KS interest, then a phase 3 trial with no advantage over placebo and a kidney-cancer study with no objective responses.
Gray-market "thymogen" adds 10 to 20 mg research vials, oral blends, and at least one listing whose formula does not match the reference chemistry. None of those products inherits the gastritis or perioperative data.
How people talk about it online
Online, thymogen is sold as an immune peptide, a thymic bioregulator, a respiratory-support product, an anti-aging supplement, and a stand-in for thymosin alpha-1. Those framings come from sellers, not from the trials.
The product layer is fragmented: 10 to 20 mg research vials, clinic reconstitution products, oral blends like "Thymogen Alpha-1" that combine Glu-Trp with Lys-Glu, and at least one listing whose stated formula mismatches the reference free-acid chemistry.
None of that answers the only question that matters for a buyer: which studied product, at which dose scale, is this vial supposed to match? The market material does not say.
Use context
Routes, doses, and cycle patterns
Thymogen regimens only make sense when the product form is named. Russian label materials use microgram-scale nasal spray or intramuscular courses, the gastritis program used oral gel twice daily for 28 days, and oncology IM-862 studies used milligram-scale intranasal drops. Vendor vials and blended supplements require matching formulation and evidence before those schedules mean anything.
Human studies and product labels
Russian intramuscular solution label
- Purpose
- Regional immunomodulatory product context
- Context
- Russian official label / OHLP
- Route
- Intramuscular
- Amount
- 100 micrograms once daily in adult label examples
- Frequency
- Once daily in the adult label pattern
- Duration
- 3 to 10 days; course total 300 to 1000 micrograms
The label also describes a 7-day adult pattern for purulent skin and soft-tissue disease. This regional label does not make research vials equivalent.
Russian nasal spray label
- Purpose
- Regional respiratory and immune-use labeling
- Context
- Russian patient leaflet / label
- Route
- Intranasal
- Amount
- 25 micrograms per spray
- Frequency
- Adults, 1 spray in each nostril twice daily in the label pattern
- Duration
- 10 days for treatment language; 3 to 5 days for prophylaxis language
Pediatric label patterns differ by age, including one-nostril dosing for younger children and once-daily use in older children.
Elderly abdominal-cancer surgery study
- Purpose
- Perioperative immune-correction and complication finding
- Context
- Double-blind randomized placebo-controlled study
- Route
- Intranasal
- Amount
- 0.1 mg per day
- Frequency
- Daily before surgery
- Duration
- 7 to 10 days before surgery
The study reported fewer postoperative complications overall in the thymogen group, but it is older, single-country evidence and too narrow for a general immune-enhancement claim.
Chronic atrophic H. pylori gastritis program
- Purpose
- Acid-function, histology, and inflammation endpoints after eradication therapy
- Context
- Multicenter randomized placebo-controlled Russian study family
- Route
- Oral gastric gel
- Amount
- Not fully specified in the available report; described as alpha-glutamyl-tryptophan gel
- Frequency
- Twice daily
- Duration
- 28 days
This is the best-described human cluster in the reports. It is local gastrointestinal evidence and does not speak for systemic wellness claims.
AIDS-related Kaposi sarcoma early IM-862 study
- Purpose
- Early oncology activity finding
- Context
- Clinical oncology study
- Route
- Intranasal drops
- Amount
- 5 mg
- Frequency
- Not reported in the public abstract
- Duration
- Not reported in the public abstract
This early finding helps explain why oncology claims exist, but later controlled oncology results weaken broad treatment claims.
AIDS-related Kaposi sarcoma phase 3 IM-862 study
- Purpose
- Placebo-controlled oncology test
- Context
- Phase 3 randomized placebo-controlled study
- Route
- Intranasal
- Amount
- IM-862 versus placebo; public abstract did not report the exact amount
- Frequency
- Public abstract did not report the frequency
- Duration
- 24 weeks
The response rate showed no significant advantage over placebo, so a cancer-treatment claim does not follow from this study.
Metastatic renal cell carcinoma phase 2 IM-862 study
- Purpose
- Single-agent oncology test
- Context
- Phase 2 study
- Route
- Intranasal
- Amount
- 20 mg
- Frequency
- Three times daily
- Duration
- 8-week cycles
The study reported stable disease in some patients but no significant objective responses, with minimal toxicity and VEGF changes.
Real-world discussion
No established community protocol
- Purpose
- Immune support discussion
- Context
- Bioregulator vendors, clinics, and forums
- Route
- Research vials and blended oral products are marketed; no consistent route pattern is documented
- Amount
- No consistent community range is documented; vendor listings show 10 mg to 20 mg research vials
- Frequency
- Not established
- Duration
- Not established
The documented regimens on this page come from Russian labels and controlled studies, not from a community protocol, and the collected material shows no consistent real-world course pattern. That is the reported picture, not advice.
What varies
- Match each claim to the document behind it: labels describe product instructions, trials report outcomes, registries show study intent, vendors show commercial claims, and user posts describe personal experience.
- Route: nasal, intramuscular, oral gel, topical cream, and reconstituted research vial contexts belong in separate comparisons.
- Amount: microgram label dosing and milligram oncology or vendor-vial amounts are too different to compare without route, formulation, and study context.
- Product identity: free acid, sodium salt, disodium salt, blend products, and mislabeled formulas change the claim.
- Duration: short label courses, 28-day gastritis treatment, and 8-week oncology cycles belong to different products and clinical goals.
Human data
Human evidence
The human evidence is real but uneven, and its strongest items point in narrow directions. The best-supported positive is the placebo-controlled Russian gastritis program: 28 days of oral alpha-glutamyl-tryptophan gel after H. pylori eradication, with acid-function, histology, and inflammatory-cell findings. A 2011 double-blind trial reported fewer postoperative complications in elderly abdominal-cancer surgery patients, but it is old, single-country, and visibly unreplicated. The oncology record mostly limits claims: the IM-862 phase 3 in AIDS-related Kaposi sarcoma found no significant benefit over placebo, and the metastatic renal cell carcinoma phase 2 found no objective responses. Broad immune enhancement, anti-aging, and cancer-control claims have no support in this record.
Evidence maturity
Thymogen holds narrow controlled-trial positives in Russia, a failed oncology program, and no FDA-approved product.
Russian and EAEU documents describe nasal spray, intramuscular, cream, and gastric-gel products with immune and infection-adjacent labeling.
A perioperative RCT in elderly abdominal-cancer surgery and a placebo-controlled chronic atrophic gastritis program reported benefits in narrow settings.
Early AIDS-KS activity as IM-862 did not survive a phase 3 placebo-controlled trial, and a renal-cell-carcinoma phase 2 found no objective responses.
U.S. status is orphan designation without approval, while gray-market vials and blended products drift from the studied formulations.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Chronic atrophic H. pylori gastritis program | Adults with chronic atrophic H. pylori gastritis after eradication therapy | Multicenter randomized placebo-controlled study family | Oral alpha-glutamyl-tryptophan gastric gel | The gastritis papers reported acid-function, gland-density, histology, inflammatory-cell, and anti-H. pylori IgG findings after 28 days of oral gel use. | The reports appear clustered around the same trial population, and the available reports do not show external replication. | moderate |
| Elderly abdominal-cancer surgery preoperative study | Elderly patients undergoing surgery for abdominal solid tumors | Double-blind randomized placebo-controlled single-center study | Intranasal thymogen before surgery | The study reported fewer postoperative complications overall and shorter postoperative stays in some subgroups after 0.1 mg/day intranasal thymogen before surgery. | Older single-country study with limited modern reporting and no clear external replication in the available reports. | limited-human |
| Older abstract-level immune and infectious-disease reports | Female genital inflammatory disease, type 1 diabetes with secondary immunodeficiency, oral candidiasis, and pulmonary tuberculosis contexts | Older abstracts, snippets, or low-detail reports | Thymogen in adjunct or disease-specific settings | Reports describe immune-marker changes or clinical improvement themes, but dose, comparator, attribution, and adverse-event detail are often hard to recover with confidence. | These reports are too limited for broad public efficacy claims. | weak |
| AIDS-related Kaposi sarcoma IM-862 studies | People with AIDS-related Kaposi sarcoma | Early clinical study followed by later randomized placebo-controlled phase 3 study | Oglufanide disodium / IM-862 intranasal oncology development | Early activity was reported, but the later phase 3 trial showed no significant response-rate advantage over placebo. | These oncology studies limit cancer claims, but they leave immune-wellness questions unanswered. | weak |
| Metastatic renal cell carcinoma IM-862 phase 2 | People with metastatic renal cell carcinoma | Small phase 2 study | Oglufanide disodium / IM-862 intranasal oncology development | The study reported stable disease in some patients, progression in most, no significant objective responses, minimal toxicity, and VEGF changes. | Small single-arm oncology study with negative objective response results. | weak |
Cautions
Safety and unknowns
- Official Russian label materials list allergic reactions for intramuscular solution and allergic-rhinitis-type symptoms for nasal spray, including edema, congestion, discharge, itching, and repeated sneezing.
- Pregnancy and lactation data are incomplete in the label materials. The spray and intramuscular labels describe use only when expected benefit outweighs risk, while the cream label treats pregnancy and breastfeeding as contraindications because clinical data are insufficient.
- Pediatric limits vary by product form. Available label summaries note that spray safety and effectiveness have not been shown below age 1 year, while intramuscular safety has not been shown below 6 months.
- Long-term systemic safety is not well characterized, especially for repeated non-label use, autoimmune disease, transplant settings, cancer immunotherapy, and high-dose gray-market exposure.
- The nasal spray leaflet notes that high-dose glucocorticoids are not recommended with thymogen because the thymogen effect may be reduced.
Product quality
A vial label is only a starting point
Identity is the main product-quality issue. Public materials include free acid, sodium salt, disodium salt, official formulations, research vials, and blended products under overlapping names.
A vendor formula or purity percentage leaves too many variables open: molecule, salt form, sterile injectable suitability, endotoxin control, fill accuracy, stability, and shipping conditions.
"Thymogen Alpha-1" is a separate blend product concept, not pure thymogen and not thymosin alpha-1.
Identity
The same name appears across alpha-glutamyl-tryptophan, oglufanide, oglufanide disodium, Timogen, and blended supplement products.
Salt form and molecular weight
The free acid and sodium or disodium forms have different chemistry and mass. A formula mismatch is a real product-warning signal.
Sterility and endotoxin
Research vials and reconstituted products raise route-specific contamination questions that a narrow purity result cannot answer.
Formulation
Nasal spray, intramuscular ampoule, cream, gastric gel, oncology drops, and vendor vials put the peptide in different delivery systems, so route and formulation have to be checked before comparing outcomes.
COA depth
A meaningful certificate would include batch-specific identity, assay, impurity, contamination, and stability documentation, not just a single purity headline.
Mechanism
How it is proposed to work
Thymogen is usually described as an immunomodulatory dipeptide. The available data suggest it can interact with immune and inflammatory signaling systems, but mechanism alone cannot carry broad health claims.
Label materials describe effects on cellular and humoral immune responses and nonspecific resistance, with rapid systemic entry for nasal or parenteral administration and peptidase cleavage into glutamic acid and tryptophan.
Cell-model work describes changes in inflammatory cytokine signaling, including TNF and IL-6 expression in THP-1 monocyte or macrophage systems and endothelial-cell responses involving IL-1alpha and ICAM-1.
Review-level material discusses proposed DNA-promoter interactions for thymogen and related short peptides. That helps explain scientific interest, but it is not a settled clinical mechanism in people.
Thymogen (Glu-Trp) is a defined dipeptide, unlike the thymalin extract mixture. It was developed from the same thymic research lineage and registered in Russia as a nasal immune preparation, with proposed immunomodulatory signaling from that literature.
FAQ
Common questions
What is thymogen?
Thymogen is a short synthetic thymic peptide registered as a nasal immune drug in Russia. It is part of the same thymic-peptide lineage as thymalin but is a defined small molecule rather than an extract mixture.
How is it used?
No consistent community protocol is documented. The concrete schedules come from Russian product labels: microgram-scale nasal spray or intramuscular courses of 3 to 10 days, not milligram injection patterns.
Is there human evidence?
Old domestic Russian clinical literature exists, but nothing meeting modern controlled-trial standards, and nothing for the wellness claims made online.
Details
Technical details
Sources
References
- 1.
NCI oglufanide entry. NCI Drug Dictionary, “oglufanide disodium”
Identity, synonym mapping, IM-862 naming
- 2.
Timogen IM label. Russian OHLP for Timogen IM solution
Injection composition, indications, dosing, pregnancy-lactation note, adverse reactions
- 3.
Timogen nasal leaflet. Russian patient leaflet for Timogen nasal spray
Spray indications, dosing, interactions, allergic-rhinitis adverse effects
- 4.
Surgery RCT. Smirnov et al., 2011, elderly abdominal-cancer surgery RCT
Perioperative study design, n, regimen, complication outcomes
- 5.
Gastritis pH-metry paper. Uspensky et al., 2022, pH-metry paper
Gastritis RCT, n, regimen, acid-function outcomes
- 6.
Gastritis histology paper. Baryshnikova et al., 2023, PubMed histology endpoint paper
Histology and gland-density outcomes in gastritis
- 7.
Gastric inflammation paper. 2022 evidence-based gastroenterology paper on inflammation
Gastric inflammatory-cell and anti-H. pylori IgG outcomes, same trial family
- 8.
AIDS-KS phase II study. Tulpule et al., 2000, JCO AIDS-KS study
Early clinical finding, 5 mg intranasal drops, 36% major responses, mild transient AEs
- 9.
AIDS-KS phase III study. Noy et al., 2005, JCO phase III AIDS-KS study
No significant placebo-beating response benefit
- 10.
RCC phase II study. Deplanque et al., 2004, Br J Cancer metastatic RCC phase II
25-patient negative single-agent oncology study, intranasal 20 mg TID, VEGF decrease
- 11.
FDA orphan designation. FDA orphan-drug designation record for oglufanide disodium
U.S. orphan designation, not FDA-approved for orphan indication
- 12.
FDA 503A nomination. FDA 503A bulk-drug-substance nomination docket entry
U.S. compounding interest is not equivalent to approval
- 13.
Thymogen vendor example. PureHealthPeptides “Thymogen” product page
Retail peptide formula and MW mismatch risk context
- 14.
Thymogen Alpha-1 blend example. Dr. Jill Health “Integrative Peptides - Thymogen Alpha-1” page
Blended supplement, not pure thymogen, plus superiority marketing language
- 15.
Regastim Gastro context. Vidal or label-style Regastim Gastro pages
Gastric formulation description and local-mucosal PK framing
- 16.
Russian thymogen market listings. Russian market listings for multiple thymogen forms
Marketed dosage forms and registration context
- 17.
Cell-model inflammation paper. Golovacheva et al., 2023, cell-model inflammation paper
IL-1alpha, IL-8, ICAM-1 mechanism evidence
- 18.
Thymalin-thymogen relationship review. Review material on the thymalin and thymogen relationship
Origin and comparison context.