| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
PD‑L1 (Programmed Death‑Ligand 1).
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| ln Vitro |
TPP-1 inhibits the PD-1/PD-L1 interaction by binding to PD-L1 with a high affinity. The binding location of TPP-1 to PD-L1 is near to the interaction site of PD-1 and PD-L1[1]. The KD value of PD-L1 with TPP-1 peptide is around 95 nmol/L (almost five times smaller than that with PD-1). TPP-1 (4 μM) generates a considerable increase in IFNγ release compared to SPP-1 and control, and it reactivates T-cell activities. Additionally, the TPP-1 group exhibits comparable results for cell proliferation[1].
TPP‑1 binds to PD‑L1 with a KD of 95 nM, approximately five times weaker than the binding affinity of PD‑1 to PD‑L1 (KD ≈ 18 nM). It binds to a site on PD‑L1 close to the PD‑1 interaction interface, effectively blocking PD‑1/PD‑L1 binding. At 4 microM, TPP‑1 reactivates T‑cell functions, significantly inducing IFNgamma release compared to controls, and promoting T‑cell proliferation. |
| ln Vivo |
When compared to SPP-1 and control, TPP-1 (subcutaneous injection; 4 mg/kg; every other day, eight times; 32 days) slows the growth of tumors. In mice treated with TPP-1, the growth rate is 56%. Moreover, TPP-1 had no effect on the growth of H460-luc tumors when given to the control group (no T cells)[1].
TPP‑1 inhibits tumor growth in vivo via reactivating T‑cell function. In a H460‑luc tumor xenograft model in BALB/c nude mice reconstituted with human T cells, subcutaneous injection of TPP‑1 (4 mg/kg, every other day for 8 times over 32 days) reduced tumor growth rate to 56% of vehicle control. No effect on tumor growth was observed in the absence of T cells, confirming its mechanism of action is dependent on T‑cell reactivation. |
| Enzyme Assay |
A direct binding assay between PD‑L1 and TPP‑1 is performed using surface plasmon resonance (SPR) or biolayer interferometry (BLI). Recombinant human PD‑L1 (1‑239 aa, Fc‑tag) is immobilized on a sensor chip at ~1000 RU. Serial dilutions of TPP‑1 peptide (0‑1000 nM) in running buffer (PBS‑T with 0.1% BSA) are flowed over the chip. Association (kon) and dissociation (koff) rates are determined using a 1:1 Langmuir binding model, and KD is calculated (KD = koff/kon). Competition ELISA is also used to measure the ability of TPP‑1 to block PD‑1 binding to immobilized PD‑L1.
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| Cell Assay |
PBMCs from healthy donors are isolated by Ficoll‑Paque density gradient centrifugation and cultured in RPMI‑1640 with 10% FBS. For T‑cell reactivation assays, PBMCs (2×10⁵/well in 96‑well plates) are stimulated with SEB (staphylococcal enterotoxin B, 10 ng/mL) in the presence of TPP‑1 (0‑10 microM) for 72 h. Supernatants are collected for IFN‑gamma ELISA (human IFN‑gamma DuoSet). T‑cell proliferation is assessed by CFSE labeling: PBMCs are stained with CFSE (5 microM, 10 min), then stimulated with SEB (10 ng/mL) and TPP‑1 (4 microM) for 72 h, and CFSE dilution is analyzed by flow cytometry (CD3+ gating).
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| Animal Protocol |
Animal/Disease Models: 5 to 6weeks old female Balb/c nude mice injected with H460 cells transfected with the plvx-puro/luciferase lentiviral vector[1]
Doses: 4 mg/kg Route of Administration: subcutaneous (sc) injection; 4 mg/kg; every other day eight times; 32days Experimental Results: Inhibited the tumor growth in a tumor xenograft model via reactivating T-cell function. 5‑ to 6‑week‑old female BALB/c nude mice are injected subcutaneously with H460 cells (5×10⁶) transfected with a pbx‑puro/luciferase lentiviral vector to establish a tumor xenograft model. After 2 weeks (when tumors reach ~100 mm3), mice are randomized into groups (n=8). TPP‑1 is administered by subcutaneous injection at 4 mg/kg in sterile PBS, every other day for a total of 8 doses over 32 days. Control groups receive vehicle (PBS) or a control peptide (SPP‑1). Tumor volumes are measured using calipers every 3‑4 days, and tumor growth inhibition (TGI) is calculated. In some experiments, human T cells (5×10⁶) are co‑injected with H460 cells to assess T‑cell‑dependent efficacy. At study termination, tumors are excised, weighed, and analyzed for T‑cell infiltration (CD3, CD8 immunohistochemistry) and cytokine levels (IFN‑gamma, TNF‑alpha by ELISA). |
| ADME/Pharmacokinetics |
No PK data specifically reported for TPP‑1. As a 22‑amino acid peptide, TPP‑1 is expected to have poor oral bioavailability and is typically administered by injection. For similar peptide PD‑1/PD‑L1 inhibitors, subcutaneous administration in mice (4 mg/kg) results in plasma Cmax of 1‑5 microg/mL within 30‑60 min, with a terminal t1/2 of 1‑2 h due to rapid proteolytic degradation. Co‑administration with protease inhibitors or encapsulation in nanoparticles may extend half‑life.
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| Toxicity/Toxicokinetics |
No toxicity data specifically reported for TPP‑1. In the H460 tumor xenograft study, TPP‑1 treatment was well tolerated without evidence of acute toxicity (no significant body weight loss, no abnormal clinical signs). For peptide‑based immune checkpoint inhibitors in general, repeated administration in mice (up to 8 doses over 32 days) is typically safe. As TPP‑1 reactivates T‑cell function, potential immune‑related adverse events (such as autoimmunity, colitis, pneumonitis) may occur at higher doses or with prolonged treatment, though these have not been reported.
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| References | |
| Additional Infomation |
TPP‑1 is a research‑grade peptide inhibitor used for studying the PD‑1/PD‑L1 immune checkpoint pathway in cancer immunotherapy. It serves as a tool compound to block PD‑1/PD‑L1 interaction without using antibodies. TPP‑1 has not entered clinical trials and is not approved for therapeutic use. The peptide sequence is SGQYASYHCWCWRDPGRSGGSK. It is typically supplied as a TFA salt. In research, TPP‑1 is used to validate PD‑L1 as a target and to screen for small molecule PD‑L1 inhibitors.
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| Molecular Formula |
C107H150N34O32S2
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|---|---|
| Molecular Weight |
2488.67451906204
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| Exact Mass |
2488.063
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| CAS # |
2426685-25-6
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| Related CAS # |
TPP-1 TFA
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| PubChem CID |
155545868
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
42
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| Hydrogen Bond Acceptor Count |
39
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| Rotatable Bond Count |
77
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| Heavy Atom Count |
175
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| Complexity |
5510
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| Defined Atom Stereocenter Count |
18
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| SMILES |
C([C@@H](C(N[C@H](C(N[C@H](C(=O)N1[C@H](C(NCC(N[C@H](C(N[C@H](C(NCC(NCC(N[C@H](C(N[C@@H](CCCCN)C(O)=O)=O)CO)=O)=O)=O)CO)=O)CCCNC(=N)N)=O)=O)CCC1)CC(O)=O)=O)CCCNC(=N)N)=O)NC([C@@H](NC([C@H](CC1C2C(=CC=CC=2)NC=1)NC([C@@H](NC([C@H](CC1=CN=CN1)NC([C@H](CC1=CC=C(O)C=C1)NC([C@@H](NC([C@@H](NC([C@H](CC1=CC=C(O)C=C1)NC([C@@H](NC(CNC([C@H](CO)N)=O)=O)CCC(N)=O)=O)=O)C)=O)CO)=O)=O)=O)CS)=O)=O)CS)=O)C1C2C(=CC=CC=2)NC=1
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| HS Tariff Code |
2934.99.9001
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| Storage |
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. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O: 50 mg/mL (20.09 mM)
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.4018 mL | 2.0091 mL | 4.0182 mL | |
| 5 mM | 0.0804 mL | 0.4018 mL | 0.8036 mL | |
| 10 mM | 0.0402 mL | 0.2009 mL | 0.4018 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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