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Educational reference only. Nothing on this page constitutes medical advice or encourages personal use of this compound. Always consult a qualified healthcare provider before any decision involving your health.

SHLP2

SHLP2 · Small Humanin-Like Peptide 2

C
Animal replicated
RouteInjectableGray-market only
C
Evidence grade: Animal replicated

Effect demonstrated in multiple animal studies; human data sparse or extrapolated. Grades summarize evidence quality, not whether a compound is appropriate, legal, or risk-free.

At a glance
What it is
Small Humanin-Like Peptide 2 — Mitochondrial-Derived Peptide (MDP) — Mitochondrial-Derived Peptide, Humanin-Like Peptide, MDP.
Why people use it
Metabolic Health and Obesity Protection · Insulin Sensitivity and Glucose Homeostasis · Prostate Cancer Biomarker · Mitochondrial Function and Anti-Aging · Cardiovascular Effects · Leptin Elevation
What the evidence supports
Observational only. The prostate cancer association study (n=200) is the primary human data. No human intervention trial for SHLP2 has been registered or completed as of May 2026. All beneficial effect data is from animal models and cell culture.
If you only read one thing

SHLP2 has the most complete mechanistic picture of any SHLP: a receptor has been identified (CXCR7 — discovered by an independent group, the strongest replication in the literature), a central nervous system mechanism has been characterized (POMC neuron activation in the hypothalamus — the same pathway used by GLP-1 drugs), and metabolic protection in obese mice has been demonstrated. Lower levels are associated with prostate cancer risk in a human observational study. The age-related decline pattern is established. And there is no human intervention trial. The entire 'beneficial effects' evidence base is animal models, cell culture, and one observational correlation. The prostate cancer connection is compelling and has attracted scientific interest. Whether restoring SHLP2 levels through exogenous injection produces the protective benefits implied by the decline correlations — that question has not been tested in a controlled human study.

Published literature
0human trials0human studies0animal0in vitro
Evidence reality check
Human evidence
No human studies
0 observational; RCT evidence not present in corpus.
Preclinical base
0 lab signals
0 animal; 0 in-vitro/mechanistic.
Best-supported use
Metabolic protection / obesity
B grade · SHLP2 protects from HFD-induced obesity; CXCR7/POMC mechanism identified. Animal only; male mice; no female or human data
Indication map
Supported / plausible / speculative / avoid
Supported
Metabolic protection / obesity
B grade · SHLP2 protects from HFD-induced obesity; CXCR7/POMC mechanism identified. Animal only; male mice; no female or human data
Supported
Insulin sensitization in vivo
B grade · Only SHLP2 (not other SHLPs) improved insulin action in vivo in clamped animals. Cohen group primary; animal model; no human RCT
Supported
Prostate cancer biomarker
B grade · Lower SHLP2 associated with PCa risk; >350 pg/mL rules out PCa with 95% accuracy. Observational; n=200; single institution; not intervention
Supported
Age-related decline correlation
B grade · SHLP2 declines with age alongside MOTS-c and Humanin. Correlation not causation; Cohen group

SHLP2 is the compound in this reference that is furthest along in its research trajectory while still being the furthest from clinical application. The mechanism is becoming clearer — a receptor has been found, a hypothalamic pathway has been identified, metabolic protection has been demonstrated. The translation to humans has not begun.

The central tension resolved: of six small humanin-like peptides discovered simultaneously in the same mitochondrial genomic neighborhood, SHLP2 emerged as the most metabolically active in vivo. A 2023 paper from an independent Chinese group identified its receptor — CXCR7 — and demonstrated that it activates POMC neurons in the hypothalamus to suppress appetite and increase thermogenesis. Lower plasma SHLP2 is associated with higher prostate cancer risk in an observational study of 200 men. All of this is preclinical or observational. No human intervention trial exists. The community using SHLP2 is making an extrapolation from compelling mechanistic and animal data to human benefit — the same extrapolation that the MDP field makes broadly, with the understanding that this is a promising compound at an early stage of characterization rather than an established therapeutic.

The strongest argument for SHLP2: the receptor has been found (CXCR7) by an independent group. The mechanism is characterized (POMC neuron activation, appetite suppression, thermogenesis) and involves the same neuronal pathway as GLP-1 drugs — one of the most clinically validated pathways in obesity medicine. Metabolic improvements in animal models have been independently replicated. The prostate cancer biomarker finding is the most specific human-biology signal in any SHLP chapter. The compound is genuinely distinct from Humanin and MOTS-c — different receptor, different primary mechanism, different application.

The strongest argument for caution: the entire beneficial effect evidence base is animal models from 2016-2023. The human data is one observational biomarker study. The dose used in community protocols is likely far below what produced effects in the animal studies. The CohBar commercial relationship creates a financial interest in positive SHLP2 research that isn't present for Humanin's neuroprotection literature (which has Japanese and other independent origins). This is the youngest and least independently validated compound in the MDP section of this reference.

Properties
Active malignancy: cautionNot injectable
Evidence
CAnimal replicated
The SHLP Family Context
SHLP1-6 were all discovered simultaneously in 2016 via in silico identification of small open reading frames in the mitochondrial 16S rRNA gene. All six were then characterized in cell culture. SHLP2 and SHLP3 showed the most Humanin-like protective effects. Only SHLP2 improved insulin action in vivo among all six. SHLP2 is the most-studied and most promising member of the family.
Discovery of Receptor — 2023
Sun et al. (Nature Communications, 2023): SHLP2 binds to and activates CXCR7 (chemokine receptor 7). This was the first identified receptor for SHLP2 and was discovered by an independent Chinese research group — the most important independent replication in SHLP2's evidence base. CXCR7 activation drives SHLP2's CNS effects, including POMC neuron activation in the hypothalamus.
Key Metabolic Effects (Animal Data)
Protected mice from high-fat diet-induced obesity when given systemically or directly into the brain. Improved insulin sensitivity via both peripheral and central mechanisms. Activated POMC neurons in the arcuate nucleus (suppressed food intake, promoted thermogenesis). Reduced markers associated with age-related metabolic disorders (sphingolipids, fatty acids). Grade B-C: animal models; some independent replication.
The Prostate Cancer Biomarker Finding
Xiao et al. (Oncotarget, 2017): In 200 men undergoing prostate biopsy (100 negative, 100 PCa cases; 100 Black and 100 white), lower serum SHLP2 was significantly associated with prostate cancer risk. SHLP2 levels >350 pg/mL ruled out PCa with ≥95% accuracy in both racial groups. This is observational human data — lower SHLP2 does not prove the peptide causes cancer protection, but the correlation is striking.
Age-Related Decline
Circulating SHLP2 levels decline with age alongside MOTS-c, Humanin, and other MDPs — confirmed by the Cohen group in multiple species. Whether supplementing exogenous SHLP2 to restore levels produces the protective effects seen with higher endogenous levels is not established.
Provenance Concentration
The discovery, in vitro characterization, animal metabolic work, and human biomarker studies are all from the Cohen group at USC Davis School of Gerontology. The 2023 Sun et al. Nature Communications paper identifying CXCR7 is the most important independent contribution — from a Chinese academic group with no USC affiliation.
Community Use
Very small community, primarily advanced MDP users who have already worked through MOTS-c and Humanin. Community dose: 0.5-2 mg SubQ, weekly or 2-3x per week. Highly experimental — smaller user base than any other compound in this reference.
FDA / Regulatory
Not FDA-approved. Not PCAC-reviewed. Research chemical only. Not a controlled substance.
WADA
Not listed on the 2026 WADA Prohibited List. Unlike MOTS-c (S4.4 explicit ban), SHLP2 has not been specifically identified for prohibition. Athletes can currently use without known WADA violation — verify current status. CohBar Inc. Pinchas Cohen is listed as a consultant and stockholder in CohBar Inc., a company developing MDP-based therapeutics. This commercial relationship applies to all MDP research including SHLP2 and should be noted when evaluating Cohen group publications.
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