CD4 receptor (ligand; no IC50/Ki/EC50 values reported)
CCR5 chemokine receptor (blocks chemotaxis; no IC50/Ki/EC50 values reported)
Potential VIP receptor interactions (no quantitative data)
No IC50, Ki, EC50, or DC50 values were reported for any target in these studies. [3][4]

Using HIV virions pseudotyped with the ADA envelope, peptide T inhibits viral entry in the MAGI cell assay and prevents infection in the luciferase reporter experiment. Peptide T, in contrast to CXC4, exclusively inhibits HIV replication by binding to the chemokine receptor CCR5 [2]. Human Th2 cell lines and PBMC produce IL-10 when exposed to peptide T at a concentration of 10-8 M. Additionally, the generation of IFN-g by PBMC was markedly suppressed by peptide T at a dose of 10-9 M [3].

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Cytokine modulation in human PBMC: Peptide T at 10⁻⁸ M significantly induced IL-10 production by human Th2 cell line and PBMC from psoriatic patients and normal individuals (P < 0.05, ANOVA). Peptide T at 10⁻⁹ M concentration significantly inhibited IFN-γ production by PHA-stimulated PBMC (P < 0.001, ANOVA). Anti-IL-10 antibody (20-50 ng/mL) inhibited the anti-IFN-γ effect of Peptide T (P < 0.05, t-test), indicating the effect was mediated through IL-10 induction. [3]
No effect on T cell proliferation in rat model: Lymph node cell proliferation assays from MBP-immunized rats treated with Peptide T showed no differences in proliferation towards MBP compared to controls, suggesting Peptide T did not affect T cell activation or proliferation in this model. [4]
No effect on cytokine production in rat model: Peptide T did not affect IL-4 or IFN-γ production by CD4+ T cells from lymph node cells stimulated with MBP (10 μg/mL) for 48 hours, as determined by flow cytometry. [4]

Subcutaneous injections of T-peptide are administered at varying doses and stages of experimental autoimmune encephalomyelitis (EAE) disease; nevertheless, T-peptide is not able to prevent or treat EAE [4].
Clinical observation in psoriasis: Peptide T has been reported to resolve psoriatic lesions when infused intralesionally in nanogram amounts. It has also shown efficacy in psoriasis and psoriatic arthritis in several reports. [3]
EAE studies in Lewis rats: In pilot studies, Peptide T (500 μg subcutaneously every 2 days) administered during the induction phase (days 1-9 post-immunization) showed milder EAE with statistically significant differences in incidence (7/12 vs 11/11; P=0.015), chronicity (3.46±3.69 vs 7.41±3.07; P=0.013), and maximum score (1.21±1.23 vs 2.41±0.77; P=0.018). However, in expanded studies with increased animal numbers, Peptide T (500 μg) administered during induction, effector, or both phases did not significantly ameliorate EAE. Only incidence was lower in the induction-phase treated group (19/25 vs 22/22; P=0.016). Doses ranging from 125-800 μg showed no consistent effect. Daily administration also showed no effect. [4]
HIV-associated conditions: Peptide T has been reported to increase IL-10 levels and decrease IFN-γ levels in adult HIV patients receiving peptide T for seven weeks. It has been studied for cognitive impairment and dementia in AIDS patients as a safe treatment, though efficacy remains controversial. [3][4]

PBMC cytokine studies: PBMC (1×10⁶ cells) from 10 psoriatic patients and 10 normal individuals were stimulated with ConA (3 μg/mL) or PHA (5 μg/mL) along with various concentrations of Peptide T (10⁻⁶ to 10⁻¹² M) for 48 hours at 37°C. Supernatants were collected and frozen at -70°C. IL-10 and IFN-γ were detected using ELISA kits. Anti-IL-10 antibody (20-50 ng/mL) was used to assess its effect on the anti-IFN-γ effect of Peptide T. [3]
Human Th2 cell line culture: A human Th2 cell line was maintained by adding feeder layer (irradiated human peripheral blood lymphocytes at 10⁶/mL, irradiated EBV-transformed B cell line at 10⁵/mL, and PHA at 0.1 μg/mL in YM¹ medium) and T cell clone at 2×10⁵/mL, incubated at 37°C in 5% CO₂. IL-2 (20 ng/mL) was added after 3-4 days. Once in synchronous growth, Peptide T at 10⁻⁶ to 10⁻¹² M was added and incubated for 48 hours; supernatants collected for IL-10 ELISA. [3]
Rat lymph node cell proliferation assays: Lymph node cells from immunized rats were cultured in triplicate at 2×10⁵ cells/well in DMEM with 5% FCS, 1% non-essential amino acids, 1% pyruvate, 2 mM glutamine, 5×10⁻⁵ M 2-mercaptoethanol, 50 U/mL penicillin and 50 μg/mL streptomycin. Cells were stimulated with 10 μg/mL MBP with and without different doses of Peptide T, incubated for 3 days (last 18-20 hours with 0.5 μCi ³H-Td), harvested, and incorporated radioactivity determined by scintillation counter. Stimulation index expressed as mean cpm of antigen-stimulated cultures divided by cpm of unstimulated cultures. [4]
Rat cytokine production measurement: LNC were stimulated with 10 μg/mL MBP for 48 hours, last 18-20 hours in presence of 2 mM monensin to avoid cytokine release. Cells were washed, permeabilized with Cytofix-Cytoperm buffer, stained with biotinylated anti-rat CD4, anti-rat IFN-γ FITC, anti-rat IL-4 PE or appropriate negative controls, and analyzed by flow cytometry. [4]

EAE induction in Lewis rats: Female Lewis rats aged 6-8 weeks were immunized with a single subcutaneous injection of 0.9% saline containing guinea pig MBP (100 μg/animal) emulsified in equal volume of Freund's incomplete adjuvant containing 4 mg/mL M. tuberculosis H37Ra. Rats were injected subcutaneously with 0.1 mL of emulsion in both hind foot flanks. [4]
Peptide T administration: Lyophilized Peptide T was resuspended in saline at appropriate concentrations. Peptide T (125, 250, 500, 800 μg) was administered subcutaneously in the hind foot flanks in a final volume of 0.2 mL. Control animals received saline alone. Treatment protocols included: induction phase (days 1, 3, 5, 7, 9 post-immunization), effector phase (days 9, 11, 13, 15), or both phases (days 1, 3, 5, 7, 9, 11, 13, 15). Daily administration was also tested. [4]
Clinical evaluation: Animals were weighed and examined daily for neurological signs using a 0-6 scale: 0=no signs, 0.5=partial tail tonus loss, 1=full tail paralysis, 2=mild paraparesis, 3=paraplegia, 4=tetraparesis, 5=moribund, 6=death. Experiments were performed blinded. [4]
Anti-peptide T antibody measurement: Serum samples were tested by ELISA. Wells coated with 5 μg/mL Peptide T in PBS, blocked with 0.1% BSA, incubated with serum dilutions (1:10 to 1:80) for 90 minutes, washed, incubated with alkaline phosphatase-conjugated anti-rat IgM and IgG (1:1000), and substrate (p-nitrophenylphosphate with diethanolamine, 1 mg/mL) added. Absorbance measured at 405 nm. [4]
Histopathology: Brain and spinal cord removed, fixed in 4% formaldehyde, cryoprotected in 30% sucrose, frozen in methyl-butane and liquid nitrogen. 8 μm sections cut on cryostat and stained with hematoxylin and eosin. [4]

In vitro toxicity: No cytotoxicity data reported. Peptide T at concentrations used (10⁻⁶ to 10⁻¹² M) did not cause cell death in PBMC or Th2 cell cultures. [3]
In vivo safety in rats: No mortality or adverse effects were reported in Lewis rats receiving Peptide T at doses up to 800 μg subcutaneously. No behavioral or physical changes were noted other than EAE clinical signs. [4]
Human safety: Peptide T has been reported to be a safe treatment in humans for HIV-associated conditions and psoriasis, with no significant safety issues identified in clinical trials. [3][4]
No LD50, plasma protein binding, organ-specific toxicity, or drug-drug interaction data were reported in these studies. [3][4]

[1]. Peptide T[4-8] is core HIV envelope sequence required for CD4 receptor attachment. Lancet. 1987 Sep 26;2(8561):751.

[2]. Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5). Antiviral Res. 2001 Oct;52(1):63-75.

[3]. Immunomodulatory effects of peptide T on Th 1/Th 2 cytokines. Int J Immunopharmacol. 1999 Sep;21(9):609-15.

[4]. Peptide T does not ameliorate experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Clin Exp Immunol. 2000 Jul;121(1):151-6.

N-(N-(N(2)-(N-(N-(N-(N-(ND-alanyl-L-seryl)-L-threonyl)-L-threonyl)-L-asparaginyl)-L-tyrosyl)-L-threonine. This octapeptide has sequence homology with the HIV envelope protein gp120 and may be used as an antiviral drug for the treatment of AIDS. Its core pentapeptide sequence TTNYT consists of amino acids 4-8 in peptide T and is a sequence necessary for the binding of the HIV envelope to the CD4 receptor.

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Background: Peptide T is a synthetic octapeptide (Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr) derived from the V2 region of HIV-1 gp120. It was discovered as a ligand for the CD4 receptor and was originally developed as a potential antiviral agent to prevent HIV binding to CD4+ T cells. Subsequently, it has been studied for various immunomodulatory properties. [3][4]
Mechanism of action: Peptide T induces IL-10 production (a potent anti-inflammatory Th2 cytokine) and inhibits IFN-γ production (a Th1 pro-inflammatory cytokine). IL-10 inhibits IL-2 and IFN-γ production from T cells and downregulates TNF-α expression in antigen-presenting cells. The anti-IFN-γ effect of Peptide T is mediated through IL-10 induction, as anti-IL-10 antibodies inhibit this effect. Peptide T also inhibits monocyte and lymphocyte chemotaxis and acts at CCR5 chemokine receptors. It may also interact with VIP receptors and somatostatin. [3][4]
Clinical applications: Peptide T has shown efficacy in psoriasis and psoriatic arthritis when infused intralesionally. It has been studied in HIV-associated cognitive impairment and dementia. It has been reported to increase IL-10 levels and suppress IFN-γ levels in HIV patients. The Th2-promoting function suggests potential benefit for Th1-mediated inflammatory diseases such as rheumatoid arthritis and ulcerative colitis. [3][4]
EAE studies: Despite immunomodulatory effects in human cells, Peptide T did not prevent or ameliorate acute EAE in Lewis rats. It did not affect T cell activation/proliferation, IL-4 production, or IFN-γ production in this model. Poor immunogenicity (low anti-peptide T antibody titers in 42% of treated animals) was noted, possibly due to the small peptide size and lack of carrier protein conjugation. The lack of effect in rats may suggest species differences in Peptide T activity. [4]

C35H55N9O16

857.861900000001

857.377

106362-32-7

Peptide T TFA;1610056-01-3

73352

White to off-white solid powder

0mmHg at 25°C

-8.6

16

17

24

60

1530

12

C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N)O

IWHCAJPPWOMXNW-LYKMMFCUSA-N

InChI=1S/C35H55N9O16/c1-13(36)28(52)40-22(12-45)31(55)41-25(15(3)47)33(57)43-26(16(4)48)34(58)42-24(14(2)46)32(56)39-21(11-23(37)51)29(53)38-20(10-18-6-8-19(50)9-7-18)30(54)44-27(17(5)49)35(59)60/h6-9,13-17,20-22,24-27,45-50H,10-12,36H2,1-5H3,(H2,37,51)(H,38,53)(H,39,56)(H,40,52)(H,41,55)(H,42,58)(H,43,57)(H,44,54)(H,59,60)/t13-,14+,15+,16+,17+,20-,21-,22-,24-,25-,26-,27-/m0/s1

(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~116.57 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)