STING

[1].Current status of intralesional agents in treatment of malignant melanoma. Ann Transl Med. 2021 Jun;9(12):1038.

With the discovery of immune checkpoint inhibitors, the prognosis of metastatic melanoma has significantly improved. Immunotherapy and targeted therapy have extended the median overall survival (OS) of patients with metastatic melanoma from 6 months to more than 3 years. However, approximately half of these patients still die due to poor disease control. Therefore, various strategies are currently being investigated to improve treatment outcomes. One such strategy is intralesional/intracranial (IT) therapy, which can directly kill tumor cells or enhance the immunogenicity of the tumor, making it more easily recognized by the immune system. The oncolytic virus Talimogene laherparepvec (T-VEC) was the first IT therapy to receive FDA approval. This article will highlight the latest advances in IT drugs currently undergoing clinical trials for melanoma. Therapies reviewed include: T-VEC, T-VEC in combination with immune checkpoint inhibitors (including ipilimumab and pembrolizumab or other drugs), RP1, OrienX010, Canerpaturev (C-REV, HF10), CAVATAK (Coxsackievirus A21, CVA21) (alone or in combination with checkpoint inhibitors), oncolytic poliovirus/rhinovirus recombinant (PVSRIPO), MG1 Malabar virus expressing MAGE-A3, VSV-IFNβTYRP1, suicide gene therapy, ONCOS-102, OBP-301 (telomerase), interferon gene pathway stimulators (STING agonists) (including DMXAA, MIW815 (ADU-S100) and MK-1454), PV-10, and Toll-like receptor (TLR) agonists (including TLR-9 agonists such as SD-101). CMP-001, IMO-2125 or tilsotolimod, AST-008 or cavrotolimod, MGN1703 or lefitolimod), CV8102, NKTR-262 plus NKTR-214, LHC165, G100, intralesional injection of interleukin-2, Daromun (L19IL2 plus L19TNF), Hiltonol (polyinosinic-polycytidylic acid cyclase inhibitor), electroporation (including calcium electroporation and plasmid interleukin-12 electroporation (pIL-12 EP)), intrathecal injection of ipilimumab, INT230-6 (cisplatin and vincristine combined with an amphiphilic permeability enhancer), TTI-621 (SIRPαFc), CD40 agonist antibodies (ABBV-927 and APX005M), antimicrobial peptide LL37 and other miscellaneous drugs. [1]

C20H22F2N10O9P2S2

710.52

710.0456

C, 33.81; H, 3.12; F, 5.35; N, 19.71; O, 20.27; P, 8.72; S, 9.02

2082743-99-3

Typically exists as solid at room temperature

-1.2

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

Typically soluble in DMSO (e.g. 10 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.)