Structure of Resiquimod
CAS No.: 144875-48-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Resiquimod (R848) is a Toll-like receptor 7 and 8 (TLR7/TLR8) agonist that can induce the maturation of human mMDSC into inflammatory macrophages.
Synonyms: R848; S28463; VML-600
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Sophie B. Jensen ; Ditte E. Jæhger ; Elizabeth Serrano-Chávez ; Hólmfríður R. Halldórsdóttir ; Trine B. Engel ; Jennifer S. Jørgensen , et al.
Abstract: Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic TME, and the poor systemic tolerability of immune activating drugs are, however, fun_x005f_x0002_damental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming an intratumoral sustained drug release depot that provides high payloads of immune stimulatory drugs selectively within the TME. The CarboCell thereby induces a hot spot for immune cell training and polarization and further drives and maintains the tumor-draining lymph nodes in an anticancer and immune activated state. Mechanistically, this transforms cancerous tissues, conse_x005f_x0002_quently generating systemic anticancer immunoreactivity. CarboCell can be injected through standard thin-needle technologies and has inherent imaging contrast which secure accurate intratumoral positioning. In particular, here we report the therapeutic performance for a dual-drug CarboCell providing sus_x005f_x0002_tained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor in preclinical tumor models in female mice.
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Sophie Jensen ; Elizabeth Serrano-Chávez ; Hólmfridur Halldórsdóttir ; Trine Engel ; Jennifer Jørgensen ; Serhii Kostrikov , et al.
Abstract: Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic, immunosuppressive TME, and the poor systemic tolerability of immune activating drugs are, however, fundamental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming a sustained drug release depot at the injection site that provides high payloads of immune stimulatory drugs selectively within the TME. The CarboCell thereby induces a hot spot for immune cell training and polarization and further drives and maintains the tumor-draining lymph nodes in an anticancer and immune activated state. Mechanistically, this transforms cancerous tissues to allow infiltration of T cells, consequently generating systemic anticancer immunoreactivity. The CarboCell technology can release multiple small molecule drugs - each with tailored release profiles - rendering it active across the broad composition of TME backgrounds. In the current study, impressive therapeutic performance is presented for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor. CarboCell can be injected through standard clinical thin-needle technologies. Its inherent magnetic resonance imaging and ultrasound visibility, and optional radiographic contrast, make it possible to validate and plan CarboCell injections across clinical imaging modalities. These features, in combination with attractive injection intervals, secure optimal patient compliance and open new possibilities for intratumoral immunotherapy accurately across basically all anatomical locations.
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CAS No. : | 144875-48-9 |
Formula : | C17H22N4O2 |
M.W : | 314.38 |
SMILES Code : | CC(O)(C)CN1C(COCC)=NC2=C1C3=CC=CC=C3N=C2N |
Synonyms : |
R848; S28463; VML-600
|
MDL No. : | MFCD00937759 |
InChI Key : | BXNMTOQRYBFHNZ-UHFFFAOYSA-N |
Pubchem ID : | 159603 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Concentration | Treated Time | Description | References |
Human neutrophils | 10 μM | 3 h | To test the inhibitory effects of 6-gingerol, 8-gingerol, and 10-gingerol on neutrophil NETosis, results showed that 10 μM of 6-gingerol and 8-gingerol significantly inhibited NETosis. | PMC7934838 |
Mouse splenic B cells | 2.5 μg/ml | 2 days | To determine if T-bet+ B cells secrete CXCL10 protein. Results showed that R848 stimulation significantly increased CXCL10 secretion by B cells compared to medium alone. | PMC9357106 |
U87MG-LTR-Luc cells | 10, 20, 40 μM | 48 h | To test the effect of Resiquimod on HIV-1 LTR transactivation, results showed that Resiquimod could induce HIV-1 LTR transactivation. | PMC9627655 |
In Vivo:
Administration | Dosage | Frequency | Description | References |
Mice | TLR7 agonist-induced lupus model | Intraperitoneal injection | 20 mg/kg | 3 times per week for 6 weeks | To evaluate the effects of 6-gingerol on NET release and autoantibody formation in a lupus mouse model, results showed that 6-gingerol significantly reduced NET levels and autoantibody levels. | PMC7934838 |
Mice | IFN-betaYFP/YFP mice | Intraperitoneal injection | 50 nM/mouse | Single dose 24 hours before imaging | To confirm that the IFN-betaYFP/YFP mouse strain was able to report IFN-beta production under stimulation | PMC6115735 |
Mice | Graft-versus-host disease (GvHD) model in B6D2F1 and B6 mice | Intraperitoneal injection | 25 mg/mouse | 48 hours and 24 hours before, or 0 hours before transplantation | To evaluate the protective effect of R848 in the GvHD model, results showed that R848 treatment significantly improved survival rates and inhibited inflammatory cytokine production. | PMC6355498 |
Mice | Systemic lupus erythematosus model | Topical application | 100 μg,100 μl | Days 0, 2, and 6, for a duration of 10 days | To evaluate the effect of the TLR7 agonist R848 on a systemic lupus erythematosus model in mice, showing that R848 treatment increased the frequency of CD69+CD4+ T cells, effector-memory CD4+ T cells, T follicular helper cells, and plasma cells. | PMC10971436 |
Mice | Normal mice | Intraperitoneal injection | 50 μg | Injected on day 0 and day 2, samples collected on day 4 | To investigate the effects of TLR7 agonist R848 on mouse B cells. Results showed that the proportion of T-bet+ CD11c+ B cells was significantly increased in R848-treated mice. | PMC9357106 |
Mice | B6.Sle1.Sle2.Sle3 (TC) and TC. Rag1-/- mice | Topical application | 100 mg,100 mL | Three times a week for 2 weeks | To assess the effect of TLR7/8 activation on gut integrity, the results showed that R848 increased gut permeability in mice with lupus susceptibility genes but not in non-autoimmune mice. | PMC10358848 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT02688478 | Allergies | Not Applicable | Recruiting | May 7, 2020 | Canada, British Columbia ... More >> University of British columbia Recruiting Vancouver, British Columbia, Canada, V5Z 1M9 Contact: Christopher Carlsten, MD, PHD 604-875-4122 carlsten@mail.ubc.ca Principal Investigator: Christopher Carlsten, MD, MPH Less << |
NCT02637219 | - | Completed | - | United States, Washington ... More >> VA Puget Sound Health Care System Seattle, Washington, United States, 98108 Less << | |
NCT02687503 | Respiratory Tract Infections | Not Applicable | Active, not recruiting | January 2019 | United States, Wisconsin ... More >> UW Health 20 S. Park Clinic Madison, Wisconsin, United States, 53715 UW Health West Towne Clinic Madison, Wisconsin, United States, 53717 Less << |
NCT02660723 | Healthy | Not Applicable | Completed | - | France ... More >> CHU de Nice, CRC, Hôpital de l'Archet 151 route de saint-antoine de ginestière Nice, Alpes-Maritimes, France, 06200 Less << |
NCT01094496 | Bladder Cancer | Phase 2 | Terminated(Portfolio prioritiz... More >>ation due to slow enrollment) Less << | October 2017 | United States, Arizona ... More >> BCG Oncology, PC Phoenix, Arizona, United States, 85032 United States, California University of California - San Diego La Jolla, California, United States, 92093 University of Southern California Norris Comprehensive Cancer Center LA-USC Medical Center Los Angeles, California, United States, 90033 United States, Colorado University of Colorado Cancer Center Aurora, Colorado, United States, 80045 United States, Florida University of Florida Gainesville, Florida, United States, 32610 Moffitt Cancer Center Tampa, Florida, United States, 33612 United States, Iowa University of Iowa Hospitals and Clinics Iowa City, Iowa, United States, 52242 United States, Kentucky University of Kentucky Markey Cancer Center Clinical Research Organization Lexington, Kentucky, United States, 40536-0093 United States, Maryland University of Maryland Greenebaum Cancer Center Baltimore, Maryland, United States, 21201 United States, Michigan Henry Ford Health System Detroit, Michigan, United States, 48202 United States, Missouri Washington University School of Medicine St. Louis, Missouri, United States, 63110 United States, New York Roswell Park Cancer Center Buffalo, New York, United States, 14263 Weill Cornell Medical College New York, New York, United States, 10021 University of Rochester Rochester, New York, United States, 14642 SUNY Upstate Medical University Syracuse, New York, United States, 13210 Syracuse VA Medical Center Syracuse, New York, United States, 13210 United States, Pennsylvania Thomas Jefferson University Philadelphia, Pennsylvania, United States, 19107 Less << |
NCT01204684 | Glioma Anapla... More >>stic Astrocytoma Anaplastic Astro-oligodendroglioma Glioblastoma Less << | Phase 2 | Active, not recruiting | October 2019 | United States, California ... More >> University of Los Angeles, California Los Angeles, California, United States, 90095 Less << |
NCT00175435 | Hepatitis B | Phase 1 Phase 2 | Completed | - | Canada, British Columbia ... More >> Vancouver General Hospital Vaccine Education Centre Vancouver, British Columbia, Canada Less << |
NCT00948961 | Advanced Malignancies | Phase 1 Phase 2 | Completed | - | United States, Connecticut ... More >> Yale Comprehensive Cancer Center New Haven, Connecticut, United States, 06519-1717 United States, Florida Mount Sinai Comprehensive Cancer Center Miami Beach, Florida, United States, 33140 United States, Michigan Henry Ford Health System Detroit, Michigan, United States, 48202 United States, New York Memorial Sloan Kettering Cancer Center New York, New York, United States, 10017 Weill Cornell Cancer Center New York, New York, United States, 10065 United States, North Carolina Carolina BioOncology Institute, PLLC Huntersville, North Carolina, United States, 28078 United States, Oregon Providence Portland Cancer Center Portland, Oregon, United States, 97213 Less << |
NCT02090374 | Allergic Rhinitis ... More >> Asthma Latent Tuberculosis Less << | Not Applicable | Completed | - | United Kingdom ... More >> Imperial Clinical Respiratory Research Unit (ICRRU), St Mary's Hospital Paddington, London, United Kingdom, W2 1NY Less << |
NCT00115141 | Warts | PHASE2 | COMPLETED | - | - |
NCT02126579 | Melanoma Meta... More >>static Melanoma Mucosal Melanoma Less << | Phase 1 Phase 2 | Recruiting | December 2018 | United States, Texas ... More >> MDAnderson Cancer Center Active, not recruiting Houston, Texas, United States, 77030 United States, Virginia University of Virginia Recruiting Charlottesville, Virginia, United States, 22908 Contact: Emily Allred, PhD 434-982-1902 eh4m@virginia.edu Contact: Alexandra Carney, MPH 434-982-6714 alc6a@virginia.edu Principal Investigator: Craig L. Slingluff, MD, M.D. Less << |
NCT01806961 | - | Terminated(sponsor decision) | - | - | |
NCT00114920 | Warts | PHASE2 | COMPLETED | - | Welborn Clinic, Evansville, In... More >>diana, 47713, United States Less << |
NCT00960752 | Melanoma | Phase 2 | Active, not recruiting | May 2019 | United States, Texas ... More >> University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030 Less << |
NCT00116662 | Warts | PHASE2 | COMPLETED | - | Arkansas, Fayetteville, Arkans... More >>as, 72703, United States|Arkansas, Little Rock, Arkansas, 72205, United States|Georgia, Newnan, Georgia, 30263, United States|Illinois, Buffalo Grove, Illinois, 60089, United States|Indiana, Lafayette, Indiana, 47904, United States|Kansas, Wichita, Kansas, 67207, United States|Massachusetts, Boston, Massachusetts, 02114, United States|Missouri, St. Louis, Missouri, 63110, United States|Utah, Layton, Utah, 84041, United States|Vermont, Burlington, Vermont, 05401, United States Less << |
NCT01806961 | - | Terminated(sponsor decision) | - | Germany ... More >> Hauttumorcentrum Charité (HTCC) Berlin, Germany Medizinisches Zentrum Bonn - Friedensplatz Bonn, Germany Hautzentrum Düsseldorf, Germany Johannes Wesling Klinikum Minden Minden, Germany KLINIKUM VEST GmbH Knappschaftskrankenhaus Recklinghausen, Germany Switzerland Universitätsspital Basel Basel, Switzerland Inselspital Bern, Switzerland Kantonsspital St.Gallen St. Gallen, Switzerland Universitaetsspital Zurich Zurich, Switzerland Less << | |
NCT00117871 | Warts | PHASE2 | COMPLETED | - | Minnesota Clinical Study Cente... More >>r, Fridley, Minnesota, 55432, United States Less << |
NCT00117923 | Warts | PHASE2 | COMPLETED | - | Oregon Medical Research Center... More >>, Portland, Oregon, 97223, United States Less << |
NCT01737580 | Influenza Vaccination in Senio... More >>rs Less << | Phase 1 | Completed | - | Canada, British Columbia ... More >> University of British Columbia Vancouver General Hospital Vancouver, British Columbia, Canada, V5Z 1M9 Less << |
NCT01808950 | Nodular Basal Cell Carcinoma | Phase 1 Phase 2 | Terminated(safety issues) | - | Germany ... More >> Hauttumorcentrum Charité (HTCC) Berlin, Germany Switzerland Universitaetsspital Zurich, Switzerland Less << |
NCT01808950 | - | Terminated(safety issues) | - | - | |
NCT00470379 | Melanoma (Skin) | Early Phase 1 | Completed | - | United States, Minnesota ... More >> Mayo Clinic Rochester, Minnesota, United States, 55905 Less << |
NCT01748747 | Recurrent Melanoma ... More >> Stage IIA Melanoma Stage IIB Melanoma Stage IIC Melanoma Stage IIIA Melanoma Stage IIIB Melanoma Stage IIIC Melanoma Stage IV Melanoma Less << | Early Phase 1 | Completed | - | United States, Minnesota ... More >> Mayo Clinic Rochester, Minnesota, United States, 55905 Less << |
NCT01676831 | Cutaneous T Cell Lymphoma | Phase 1 Phase 2 | Unknown | - | United States, Pennsylvania ... More >> University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104 Less << |
NCT00821652 | Tumors | Phase 1 | Completed | - | United States, New York ... More >> Icahn School of Medicine at Mount Sinai New York, New York, United States, 10029 Less << |
NCT01583816 | Actinic Keratosis | Phase 2 | Completed | - | Germany ... More >> Hauttumorcentrum Charité (HTCC) Berlin, Germany Medizinisches Zentrum Bonn - Friedensplatz Bonn, Germany Hautzentrum Düsseldorf, Germany Johannes Wesling Klinikum Minden Minden, Germany KLINIKUM VEST GmbH Knappschaftskrankenhaus Recklinghausen, Germany Switzerland Kantonsspital Aarau Aarau, Switzerland Universitätsspital Basel Basel, Switzerland Inselspital Bern, Switzerland Kantonsspital St.Gallen St. Gallen, Switzerland Universitaetsspital Zurich Zurich, Switzerland Less << |
NCT00116675 | Warts | PHASE2 | COMPLETED | 2025-04-06 | Children's Clinic of Jonesboro... More >>, PA, Jonesboro, Arkansas, 72401, United States|University of California - San Francisco, San Francisco, California, 94143, United States|Longmont Clinic/Longmont Medical Research Network, Longmont, Colorado, 80501, United States|Mercy Health Research, St. Louis, Missouri, 63141, United States|Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, 03756, United States|Rhode Island Hospital - Jane Brown Building, Providence, Rhode Island, 02903, United States|DermResearch, Inc., Austin, Texas, 78759, United States|Alpine Pediatrics, Pleasant Grove, Utah, 84062, United States|Walla Walla Clinic, Walla Walla, Washington, 99362, United States|Advanced Healthcare, Milwaukee, Wisconsin, 53209, United States Less << |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
3.18mL 0.64mL 0.32mL |
15.90mL 3.18mL 1.59mL |
31.81mL 6.36mL 3.18mL |