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Golotimod (Orilotimod, SCV-07), is a potent and orally bioavailable synthetic peptide with an immunomodulating and antimicrobial activities. It contains the amino acids D-glutamine and L-tryptophan connected by a gamma-glutamyl linkage with potential immunostimulating, antimicrobial and antineoplastic activities. The exact mechanism of action is unknown, but golotimod appears to inhibit the expression of STAT-3, reversing immunosuppression and stimulating an anti-tumor immune response. This agent may stimulate the production of T-lymphocytes (in particular the helper T [Th1] cells), activate macrophages, and increase levels of interleukin 2 and interferon gamma. STAT-3, a transcription factor upregulated in many cancer cell types, is involved in tumor cell growth and survival and immunosuppression. Check for active clinical trials or closed clinical trials using this agent.
Physicochemical Properties
| Molecular Formula | C16H19N3O5 |
| Molecular Weight | 333.33916 |
| Exact Mass | 333.132 |
| CAS # | 229305-39-9 |
| Related CAS # | Golotimod hydrochloride;1029401-59-9;Golotimod TFA;2828433-07-2 |
| PubChem CID | 6992140 |
| Appearance | White to off-white solid powder |
| Density | 1.428g/cm3 |
| Boiling Point | 737.3ºC at 760 mmHg |
| Flash Point | 399.7ºC |
| Vapour Pressure | 7.99E-23mmHg at 25°C |
| Index of Refraction | 1.659 |
| LogP | 1.563 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 24 |
| Complexity | 484 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)CC[C@H](C(=O)O)N |
| InChi Key | CATMPQFFVNKDEY-YPMHNXCESA-N |
| InChi Code | InChI=1S/C16H19N3O5/c17-11(15(21)22)5-6-14(20)19-13(16(23)24)7-9-8-18-12-4-2-1-3-10(9)12/h1-4,8,11,13,18H,5-7,17H2,(H,19,20)(H,21,22)(H,23,24)/t11-,13+/m1/s1 |
| Chemical Name | (R)-2-amino-5-(((S)-1-carboxy-2-(1H-indol-3-yl)ethyl)amino)-5-oxopentanoic acid |
| Synonyms | SCV 07 SCV-07 SCV07 gammaDglutamylLtryptophan. |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vivo | Significantly, oral SCV-07 (oral gavage or subcutaneous injection, 100 μg/kg, 5 days) was found to be more effective than SCV Greater incidence and reduced severity -07 when administered after fasting in female Hartley guinea pigs [1]. Golotimod (SCV-07) is a medication used to treat experimental recurrent genital HSV-2 disease. In male LVG golden Syrian hamsters, golotimod (SCV-07) (subcutaneous injection, 100 μg/kg once or twice daily on days 1 to 20) shortens the length of ulcers and lessens the severity and severity of acute and chronic oral radiation mucositis (OM)[3]. |
| Animal Protocol |
Animal/Disease Models: Female Hartley guinea pig (250-300 g) infected with HSV-2[1] Doses: 100 μg/kg Route of Administration: po (oral gavage) or subcutaneous injection; 5-day Experimental Results: Oral administration diminished the incidence of lesions from 55 % (1 week before treatment) was diminished to only 18%, whereas subcutaneous injection of SCV-07 did not Dramatically reduce the incidence of lesions. Animal/Disease Models: Male LVG golden Syrian hamster, weighing about 80 grams, suffering from radiation mucositis [3] Doses: 10, 100μg/kg or 1mg/kg Route of Administration: subcutaneous injection; 200mg/kg. Once or twice (two times) daily from day 1 to day 20 Experimental Results: On day 18, the control group had a peak mucositis score of 3.0, while the test group had only 2.2, and the SCV-07-treated hamsters had a mucositis score of only 6.3%. At a dose of 100 μg/kg, the mortality rate in the control group was diminished to 28.1%. Doses of 10 μg/kg, 100 μg/kg or 1 mg/kg Dramatically diminished the severity and duration of oral mucositis (OM). |
| References |
[1]. An immunomodulating dipeptide, SCV-07, is a potential therapeutic for recurrent genital herpes simplex virus type 2 (HSV-2). Int J Antimicrob Agents. 2008 Sep;32(3):262-6. [2]. The STAT3 pathway as a therapeutic target in head and neck cancer: Barriers and innovations. Oral Oncol. 2016 May;56:84-92. [3]. Attenuation of radiation- and chemoradiation-induced mucositis using gamma-D-glutamyl-L-tryptophan (SCV-07). Oral Dis. 2010 Oct;16(7):655-60. |
| Additional Infomation |
Golotimod is a dipeptide. SCV-07 (g -D-glutamyl-L-tryptophan) is a novel synthetic dipeptide that acts broadly on the Toll-like receptor pathway. It has been shown to stimulate T-lymphocyte differentiation, macrocytic phagocytosis, and specific immune responses, and enhance IL-2 and INF-g production. Due to this preferential activation of Th1 cytokine production, SCV-07 may show utility in treatment of tuberculosis. It can be administered orally or subcutaneously. In independent studies, treatment of tuberculosis with SCV-07 improved clearance of mycobacteria, improved cavity healing, improvements in immune parameters and reduced symptoms (fever, weakness, sweating, dry cough, productive cough, dyspnea, chest pain, tachycardia) without any adverse local or general effects. SCV-07 has shown efficacy in treating various viral and bacterial infections. Golotimod is an orally bioavailable synthetic peptide containing the amino acids D-glutamine and L-tryptophan connected by a gamma-glutamyl linkage with potential immunostimulating, antimicrobial and antineoplastic activities. Although the exact mechanism of action is unknown, golotimod appears to inhibit the expression of STAT-3, reversing immunosuppression and stimulating an anti-tumor immune response. This agent may stimulate the production of T-lymphocytes, in particular the helper T (Th1) cells, activate macrophages, and increase levels of interleukin 2 and interferon gamma. STAT-3, a transcription factor upregulated in many cancer cell types, is involved in tumor cell growth and survival and immunosuppression. Drug Indication Investigated for use/treatment in hepatitis (viral, C), infectious and parasitic disease (unspecified), and tuberculosis. Mechanism of Action SCV-07 (g -D-glutamyl-L-tryptophan) has broad effects on the Toll-like receptor (TLR) pathway. Pharmacodynamics SCV-07 (g -D-glutamyl-L-tryptophan) is a novel synthetic dipeptide that acts broadly on the Toll-like receptor pathway. It has been shown to stimulate T-lymphocyte differentiation, macrocytic phagocytosis, and specific immune responses, and enhance IL-2 and INF-g production. |
Solubility Data
| Solubility (In Vitro) | H2O : ~125 mg/mL (~374.99 mM) |
| 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 (e.g. IP/IV/IM/SC) 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). 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) 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). 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9999 mL | 14.9997 mL | 29.9994 mL | |
| 5 mM | 0.6000 mL | 2.9999 mL | 5.9999 mL | |
| 10 mM | 0.3000 mL | 1.5000 mL | 2.9999 mL |