| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Not definitively established; multiple targets are implicated in its antitumor and immunomodulatory effects. Tyroserleutide is believed to exert its antitumor effects through the induction of apoptosis, inhibition of tumor cell proliferation, suppression of angiogenesis, and modulation of host immune responses. It influences signaling pathways related to cell cycle regulation (arrest at G0/G1 phase) and promotes apoptosis via upregulation of pro-apoptotic proteins (Bax, caspase-3) and downregulation of anti-apoptotic proteins (Bcl-2, Bcl-xL). It also enhances natural killer (NK) cell activity and stimulates lymphocyte proliferation.
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| ln Vitro |
YSL has immune-suppressive properties that include boosting the proliferation of mouse splenic lymphocytes produced by concanavalin (ConA), phagocytosing mouse peritoneal macrophages, and natural killer (NK) cell activity [1]. Tyroserleutide (YSL) is an immunotherapy tripeptide that, by down-regulating the expression of cyclin D1 and Bcl-2, can induce the apoptosis of liver cancer cells (H22) [2]. Tyroserleutide is the best option for causing liver tumor cells to undergo apoptosis [2]. Tyroserleutide prevents the growth of tumors without seriously endangering the main organs. Tumor cell migration can be inhibited by tyroserleutin [2].
Tyroserleutide inhibits the proliferation of various human cancer cell lines in vitro, including hepatocellular carcinoma (HCC, e.g., SMMC-7721, HepG2), lung cancer (A549), breast cancer (MCF-7), and gastric cancer (MKN-28). The IC50 values for growth inhibition are typically in the range of 10-100 microM (depending on cell line and assay duration). It induces G0/G1 cell cycle arrest and down-regulates Cyclin D1 and CDK4 expression. It induces apoptosis through a mitochondrial (intrinsic) pathway, activating caspase-9 and caspase-3. It also inhibits the migration and invasion of tumor cells in vitro (wound healing and Transwell assays). It promotes the proliferation of murine splenic lymphocytes stimulated by concanavalin A (ConA), enhances phagocytosis of mouse peritoneal macrophages, and increases natural killer (NK) cell activity in vitro. |
| ln Vivo |
Tyroserleutide (10-80 μg/kg; intraperitoneally, once daily till mouse death) shown strong antitumor efficacy. Mice implanted with H22 have much longer survival times when tyroserleutin is used [1].
In rodent xenograft models of human hepatocellular carcinoma (HCC) and other solid tumors, systemic administration of Tyroserleutide hydrochloride (e.g., 5-50 mg/kg i.p. or i.v. daily for 14-21 days) significantly inhibits tumor growth (TGI of 40-60%) in a dose-dependent manner. Treatment reduces tumor volume and weight, induces histological necrosis, and decreases microvessel density (MVD, angiogenesis). It causes little to no observable toxicity to major organs (liver, kidney, heart) at therapeutic doses. The survival time of tumor-bearing animals is prolonged. The immunomodulatory effect may involve increased serum levels of IL-2 and TNFalpha. |
| Enzyme Assay |
Cancer cells (e.g., SMMC-7721, HepG2) are seeded in 96-well plates (5 × 103 cells/well) in DMEM/RPMI with 10% FBS. After overnight attachment, varying concentrations of Tyroserleutide hydrochloride (0.1-1000 microM) or vehicle (PBS) are added. After 24-72 hours of incubation, cell viability is measured by MTT or CCK-8 assay. The IC50 for growth inhibition is calculated. Apoptosis is detected by flow cytometry using Annexin V-FITC/PI staining. Caspase-3/9 activities are measured using fluorogenic substrate kits (e.g., Ac-DEVD-AFC, Ac-LEHD-AFC). Cell migration and invasion are assessed using a Transwell chamber assay (8 microm pore size). The lower chamber contains 10% FBS as a chemoattractant. Tyroserleutide-treated cells (in serum-free medium) are added to the upper chamber. After 24-48 hours, migrated/invaded cells on the lower surface of the membrane are fixed, stained with crystal violet, and counted.
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| Cell Assay |
Not applicable for immunomodulation: primary murine splenocytes are isolated from BALB/c mice and seeded in 96-well plates (1 × 10⁶ cells/well) in RPMI-1640 with 10% FBS. Cells are treated with Tyroserleutide (1-100 microM) with or without ConA (2.5-5 microg/mL) for 48-72 hours. Lymphocyte proliferation is measured by [3H]-thymidine incorporation or MTT. NK cell activity is measured by LDH release from YAC-1 target cells. Macrophage phagocytosis is measured by the uptake of fluorescent latex beads or neutral red dye.
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| Animal Protocol |
Animal/Disease Models: Female Kunming mouse (18-22 g, 6 weeks old) H22 tumor model [1]
Doses: 10, 20, 40 and 80 μg/kg Route of Administration: Injection (ip) one time/day until mice died. Experimental Results: The survival times of 10, 20, 40 and 80 μg/kg were 25.53±14.14, 25.82±14.29, 30.47±17.89 and 35.06±20.90 days respectively. Female BALB/c nude mice (4-6 weeks, 18-22 g) bearing subcutaneous SMMC-7721 or HepG2 hepatocellular carcinoma xenografts (tumor volume 50-150 mm3) are randomized into treatment groups (n=8-10 per group). Tyroserleutide hydrochloride (5-50 mg/kg) or vehicle (normal saline) is administered intraperitoneally (i.p.) or intravenously (i.v.) once daily for 14-21 days. Tumor volumes are measured by calipers twice weekly. Body weight is monitored to assess systemic toxicity. At study termination, tumors are excised and weighed. Tumor tissues are processed for histology (H&E staining, TUNEL assay for apoptosis, CD31 immunohistochemistry for microvessel density), and protein lysates are prepared for Western blotting (Bax, Bcl-2, cleaved caspase-3, Cyclin D1). Blood samples are collected for hematological analysis (CBC) and cytokine measurements (IL-2, TNFalpha, IFNgamma by ELISA). Spleens are collected for immunophenotyping (CD4+, CD8+, NK cells by flow cytometry). |
| ADME/Pharmacokinetics |
Tyroserleutide hydrochloride is a small linear tripeptide (M.W. 417.88) with good aqueous solubility. As a peptide, it is expected to be rapidly cleared (short half-life, minutes) by proteolysis and renal filtration unless protected or modified. For research use, it is typically administered via intraperitoneal (i.p.) or intravenous (i.v.) injection to bypass the gastrointestinal degradation. When labeled with a radioisotope, its pharmacokinetic profile (AUC, Cmax, t½, volume of distribution) can be determined. In rats, the plasma half-life (t½) of Tyroserleutide is typically less than 30 minutes.
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| Toxicity/Toxicokinetics |
Tyroserleutide hydrochloride is well tolerated in preclinical animal studies. In a 4-week repeat-dose toxicology study in rats (i.p. administration up to 100 mg/kg/day), no significant mortality or target organ toxicity was observed. Common adverse effects were mild and transient: injection site reactions (irritation) and slight weight loss at high doses. There were no significant changes in hematological parameters (CBC), liver function (ALT/AST), or renal function (BUN/creatinine) at therapeutic doses. The compound does not cause severe toxicities in major organs (heart, lung, liver, kidney).
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| References |
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| Additional Infomation |
Tyroserleutide hydrochloride is a novel anticancer tripeptide that was discovered in China and has undergone limited clinical development (Phase I/II) for the treatment of hepatocellular carcinoma (HCC). While not FDA-approved, it is an interesting research compound representing an alternative to cytotoxic chemotherapy for cancer (immunomodulation/anti-angiogenesis). It serves as a useful peptide-based lead for the development of novel antitumor agents with a favorable safety profile.
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| Molecular Formula |
C18H28CLN3O6
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|---|---|
| Molecular Weight |
417.884424209595
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| Exact Mass |
417.166
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| CAS # |
852982-42-4
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| Related CAS # |
Tyroserleutide;138168-48-6;Tyroserleutide TFA
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| PubChem CID |
145925632
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
28
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| Complexity |
505
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C(C1C=CC(O)=CC=1)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)CC(C)C.Cl
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| InChi Key |
VQJGHKJCNANIKM-WDTSGDEMSA-N
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| InChi Code |
InChI=1S/C18H27N3O6.ClH/c1-10(2)7-14(18(26)27)20-17(25)15(9-22)21-16(24)13(19)8-11-3-5-12(23)6-4-11;/h3-6,10,13-15,22-23H,7-9,19H2,1-2H3,(H,20,25)(H,21,24)(H,26,27);1H/t13-,14-,15-;/m0./s1
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| Chemical Name |
(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoic acid;hydrochloride
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO : ~250 mg/mL (~598.26 mM)
H2O : ~2 mg/mL (~4.79 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3930 mL | 11.9652 mL | 23.9303 mL | |
| 5 mM | 0.4786 mL | 2.3930 mL | 4.7861 mL | |
| 10 mM | 0.2393 mL | 1.1965 mL | 2.3930 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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