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| Targets |
FGFR3 K650M-FGFR3 K644E FGFR3
FGFR3 (fibroblast growth factor receptor 3). VSPPLTLGQLLS is a small peptide inhibitor that binds to FGFR3, preventing its activation and subsequent phosphorylation, thereby blocking downstream signaling pathways involved in cell proliferation, migration, and tube formation. |
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| ln Vitro |
Human primary lymphatic endothelial cell (LEC) proliferation, migration, and tubule formation are inhibited by VSPPLTLGQLLS (5 μM and 10 μM; 24 h and 48 h)[1]. In addition to being successfully shown to inhibit FGFR3 phosphorylation in LECs, VSPPLTLGQLLS has also been shown to be effective in explanted metatarsal bone cultures, 293T cells, ATDC5 chondrogenic cells, and an in vivo mouse model of thanatophoric dysplasia II[1][2]. Tyrosine kinase activity of FGFR3 and its typical downstream molecules, extracellular signal-regulated kinase/mitogen-activated protein kinase, are inhibited by VSPPLTLGQLLS (10 μM; 6 h)[2]. Additionally, VSPPLTLGQLLS (0, 1, 10, and 50 μM; 24 hours and 3 or 7 days, respectively) stimulates the growth and chondrogenic differentiation of ATDC5 chondrogenic cells that have been cultured[2]. The ERK/MAPK pathway is inhibited in the FGFR3-expressing chondrocytic cell line ATDC5 by VSPPLTLGQLLS (10 μM; 0-60 min)[2].
VSPPLTLGQLLS inhibits FGFR3 phosphorylation in a concentration-dependent manner. It effectively blocks 9-cisRA-induced tracheal lymphangiogenesis and suppresses lymphatic endothelial cell (LEC) proliferation, migration, and tube formation. These activities confirm its role as an FGFR3 signaling inhibitor in the lymphatic system. |
| ln Vivo |
VSPPLTLGQLLS (1 mM; intranasal dropping; onced daily for 7 d) blocks 9-cisRA-induced lymphangiogenesis in vivo, while 9-cisRA is an isoform of vitamin A involving in AIDS-related Kaposi Sarcoma[1]. VSPPLTLGQLLS alleviates the bone growth retardation in bone rudiments from mice mimicking human thanatophoric dysplasia type II (TDII), reversed the neonatal lethality of TDII mice[2].
In an animal model of tracheal lymphangiogenesis induced by 9-cisRA, VSPPLTLGQLLS significantly blocks new lymphatic vessel formation. This in vivo efficacy suggests potential for studying conditions where pathological lymphangiogenesis occurs, such as tumor metastasis and inflammatory diseases, though primarily a research tool. |
| Enzyme Assay |
Cell-free FGFR3 kinase inhibition assays can be performed using recombinant FGFR3 enzyme and a peptide substrate. The peptide inhibitor is added to the reaction mix. Phosphorylation is measured using a luminescence-based ADP detection kit. Alternatively, binding affinity can be assessed by surface plasmon resonance (SPR) with immobilized FGFR3.
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| Cell Assay |
Western Blot Analysis[1][2]
Cell Types: Human primary lymphatic endothelial cell (LEC) s; ATDC5 chondrogenic cells Tested Concentrations: 10 μM Incubation Duration: 0, 5, 10, 30, 45, 60 min Experimental Results: Inhibited FGFR3 phosphorylation at Tyr 724 in human primary lymphatic endothelial cells (LEC)s. Inhibited the FGF2-mediated ERK/ MAPK phosphorylation in FGFR3-expressing chondrocytic cell line ATDC5. Cell Proliferation Assay[1] Cell Types: Human primary lymphatic endothelial cell (LEC)s Tested Concentrations: 2.5 μM, 5 μM, and 10 μM Incubation Duration: 15 min for pre-incubation and co-incubation with 1 μM 9-cisRA for 48 hr Experimental Results: Inhibited LEC proliferation. Cell Migration Assay [1] Cell Types: Human primary lymphatic endothelial cells (LEC)s Tested Concentrations: 5 μM Incubation Duration: 15 min for pre-incubation and co-incubation with 1 μM 9-cisRA for 24 hr; observed at 0, 24, 48 hr Experimental Results: Inhibited LEC migration tubule formation. Lymphatic endothelial cells (LECs) are seeded in 96-well plates and pre-treated with VSPPLTLGQLLS, then stimulated with 9-cisRA to induce activation. FGFR3 phosphorylation is measured by Western blot. Cell proliferation is assessed by BrdU or MTT assay. Migration is measured using a transwell chamber, and tube formation is assessed by plating on Matrigel. |
| Animal Protocol |
Animal/Disease Models: Lymphatic reporter mice, Prox1-GFP model[1]
Doses: 1 mM Route of Administration: Intranasal dropping; one time/day for 7 days; accompanied with 1 mM 9-cisRA or not Experimental Results: Dramatically inhibited total lymphatic vessel length and number of sprouts compared increase induced by 9-cisRA. Animal/Disease Models: Fgfr3Neo-K644E/+EIIa-Cre mice (TDII mice ) from Fgfr3Neo-K644E/+ mice crossed with heterozygous EIIa-Cre mice[2] Doses: 10 μM Route of Administration: Treated for 7 days Experimental Results: Suppressed FGFR3-mediated growth inhibition in cultured murine metatarsal bones. Rescued the lethal phenotype in thanatophoric dysplasia type II (TDII) mice. Rescued the abnormal growth plate and the lung phenotypes in the TDII mice. For in vivo studies, an animal model of tracheal lymphangiogenesis is used. Mice are treated with 9-cisRA to induce tracheal lymphangiogenesis, and VSPPLTLGQLLS is administered locally or systemically. After the study period, tracheas are collected and whole-mount stained with anti-LYVE-1 antibody to visualize lymphatic vessels. Lymphatic vessel density is quantified. |
| ADME/Pharmacokinetics |
VSPPLTLGQLLS is a peptide and as such is not orally bioavailable. It is typically administered locally or systemically by injection. Its half-life in vivo is short due to rapid degradation by proteases. The molecular weight is 1224.45 (C56H97N13O17). Solubility: DMSO (10-25 mg/mL) and water (1-2 mg/mL). Storage: -20degC.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for VSPPLTLGQLLS. As a peptide that targets FGFR3, off-target effects are likely minimal due to its specificity. At research doses, no overt toxicity has been reported. The compound is for research use only and is not an approved drug.
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| References |
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| Additional Infomation |
Other information: VSPPLTLGQLLS (CAS 1206896-24-3) is a research-grade peptide, not FDA-approved. It is a small peptide FGFR3 inhibitor that blocks FGFR3 phosphorylation and inhibits 9-cisRA-induced tracheal lymphangiogenesis. It is a valuable tool for studying FGFR3 function in lymphatic biology. For research use only.
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| Molecular Formula |
C56H97N13O17
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|---|---|
| Molecular Weight |
1224.44629454613
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| Exact Mass |
1223.712
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| CAS # |
1206896-24-3
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| Related CAS # |
VSPPLTLGQLLS TFA
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| PubChem CID |
165437304
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| Appearance |
White to off-white solid powder
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| LogP |
-3.2
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| Hydrogen Bond Donor Count |
15
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
36
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| Heavy Atom Count |
86
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| Complexity |
2370
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| Defined Atom Stereocenter Count |
12
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| SMILES |
C(N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)O)([C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@@H](N)C(C)C)=O
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| InChi Key |
TUBMLSKMKPKVBN-KYMYZPJVSA-N
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| InChi Code |
InChI=1S/C56H97N13O17/c1-27(2)20-34(46(75)59-24-43(74)60-33(16-17-42(57)73)47(76)61-35(21-28(3)4)48(77)62-36(22-29(5)6)49(78)66-39(26-71)56(85)86)64-53(82)45(32(11)72)67-50(79)37(23-30(7)8)63-51(80)40-14-12-18-68(40)55(84)41-15-13-19-69(41)54(83)38(25-70)65-52(81)44(58)31(9)10/h27-41,44-45,70-72H,12-26,58H2,1-11H3,(H2,57,73)(H,59,75)(H,60,74)(H,61,76)(H,62,77)(H,63,80)(H,64,82)(H,65,81)(H,66,78)(H,67,79)(H,85,86)/t32-,33+,34+,35+,36+,37+,38+,39+,40+,41+,44+,45+/m1/s1
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| Chemical Name |
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoic acid
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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) |
H2O: 50 mg/mL (40.83 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 | 0.8167 mL | 4.0835 mL | 8.1669 mL | |
| 5 mM | 0.1633 mL | 0.8167 mL | 1.6334 mL | |
| 10 mM | 0.0817 mL | 0.4083 mL | 0.8167 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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