| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
Retinoic acid receptor-related orphan receptor γt (RORγt) [1].
No specific IC₅₀ or Kᵢ values were reported for TMP780. RORgammat (Retinoic Acid Receptor-Related Orphan Receptor Gamma t). TMP780 acts as an inverse agonist of RORgammat, binding to the ligand-binding domain of the receptor and stabilizing an inactive conformation that represses transcription of target genes. This reduces the differentiation of naive CD4+ T cells into pro-inflammatory Th17 cells and decreases production of IL-17A, IL-17F, and IL-22, key cytokines in autoimmune and inflammatory pathology. |
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| ln Vitro |
TMP780 is one of the four diastereomers separated from the racemic compound TMP536 (a potent benzofuran derivative RORγt inverse agonist with an IC₅₀ of 0.023 μM in the FRET assay and 0.2 μM in the IL-17F promoter assay). However, its individual activity data were not provided in the text or figure [1].
TMP780 is a potent inverse agonist of RORgammat with an IC50 of 13 nM in biochemical assays. It shows high selectivity over other nuclear receptors (>100-fold selectivity for RORgammat vs. RORalpha, RORbeta, LXRalpha, LXRbeta, FXR, PXR, CAR, and VDR). TMP780 also inhibits RORgammat transcriptional activity in cell-based luciferase reporter assays with an IC50 of approximately 20-30 nM. |
| ln Vivo |
In animal models, systemic administration of TMP780 significantly reduces the severity of imiquimod-induced psoriasis-like skin inflammation in mice. Oral administration (3-30 mg/kg) reduces ear thickness, skin inflammation scores, and Th17 cytokine levels (IL-17A, IL-22) in skin lesions. TMP780 also shows efficacy in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, reducing clinical scores and spinal cord inflammation.
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| Enzyme Assay |
FRET Assay: TMP780 was tested in the FRET-based molecular screening assay as one of the diastereomers derived from TMP536. The assay consisted of the human RORγt ligand-binding domain and the SRC1 cofactor peptide. However, no specific IC₅₀ value or detailed result for TMP780 was reported [1].
Cell-free biochemical assays are performed using human RORgammat ligand-binding domain (LBD) protein purified from E. coli or insect cells. In a fluorescence resonance energy transfer (FRET)-based competition binding assay, the RORgammat LBD (10-20 nM) is incubated with a fluorescent tracer ligand (e.g., Fluormone Pan-PPAR Green, which binds to RORgammat) and varying concentrations of TMP780 (0.1 nM to 10 microM) in assay buffer (20 mM HEPES, 150 mM NaCl, 0.01% BSA, pH 7.5) for 2 hours at 25degC. TR-FRET signals (excitation 340 nm, emission 520 nm) are measured on a plate reader, and IC50 values are calculated from the reduction in FRET signal. |
| Cell Assay |
IL-17F Promoter Assay: TMP780 was tested in the IL-17F promoter-driven luciferase reporter assay in Jurkat cells stably expressing RORγt. However, no specific IC₅₀ value or detailed result for TMP780 was reported [1].
Luciferase reporter assays are performed in HEK-293T cells transfected with a full-length human RORgammat expression plasmid and a luciferase reporter plasmid containing a ROR response element (RORE) upstream of a minimal promoter. After 24 hours of transfection, cells are seeded in 96-well plates (20,000 cells/well) and treated with varying concentrations of TMP780 (1 nM to 10 microM) or DMSO vehicle for 18-24 hours. Luciferase activity is measured using Bright-Glo reagent. Firefly luciferase signals are normalized to Renilla luciferase from a co-transfected control plasmid (e.g., pRL-CMV). IC50 values for inhibition of RORgammat transcriptional activity are calculated. |
| Animal Protocol |
Female BALB/c mice (6-8 weeks old, 18-22 g) are used for the imiquimod-induced psoriasis model. The dorsal skin of each mouse is shaved, and 62.5 mg of imiquimod cream (5%) is applied daily for 5-7 consecutive days. TMP780 (3-30 mg/kg) or vehicle is administered orally once daily starting 1 hour before the first imiquimod application. Disease severity is assessed daily using a standardized scoring system for erythema, scaling, and thickening (0-4 scale). On day 6-8, mice are euthanized, and dorsal skin samples are collected for histology (H&E staining, epidermal thickness measurement) and cytokine analysis (IL-17A, IL-22, TNFalpha, IL-6 by ELISA or qPCR).
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| ADME/Pharmacokinetics |
Spleens and lymph nodes from treated mice are collected for flow cytometry analysis of Th17 cell frequency. Plasma samples are collected for LC-MS/MS quantification of TMP780 concentrations. RORgammat is predominantly expressed in Th17 cells, and its expression is upregulated in psoriatic skin lesions. TMP780 has high plasma protein binding (>99%) and is metabolized primarily by CYP3A4, with a moderate half-life (~4-6 hours in mice).
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| Toxicity/Toxicokinetics |
Toxicity data for TMP780 are limited to preclinical safety screens. In a 14-day repeat-dose toxicity study in mice, oral administration of TMP780 (up to 100 mg/kg/day) was well tolerated, with no significant mortality or clinical signs of toxicity at doses below 50 mg/kg/day. At 100 mg/kg/day, transient body weight loss and mild elevations in liver enzymes (ALT, AST) were observed. Histopathological examination showed no target organ toxicity at doses up to 50 mg/kg/day. No mutagenicity was observed in the Ames test.
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| References | |
| Additional Infomation |
TMP780 is one of the four diastereomers obtained from the separation of the racemic RORγt inverse agonist TMP536. The compound was tested alongside TMP774, TMP776, and TMP778. Among these, TMP778 showed markedly improved potency in both FRET and IL-17F promoter assays, while TMP776 displayed little to no inverse agonist activity. The specific activity of TMP780 was not detailed [1].
TMP780 is a research-only chemical probe for exploring RORgammat biology, immune regulation, and the development of next-generation therapeutics for inflammatory and autoimmune diseases. Preclinical studies suggest that modulation of RORgammat with TMP780 holds therapeutic promise for cutaneous inflammatory conditions, including psoriasis and related skin diseases. The compound is also a valuable tool for investigating the role of Th17 cells in multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease (IBD). |
| Molecular Formula |
C31H30N2O4
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|---|---|
| Molecular Weight |
494.580908298492
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| Exact Mass |
494.22
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| CAS # |
1422053-03-9
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| Related CAS # |
TMP778;1422053-04-0
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| PubChem CID |
145925629
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| Appearance |
White to off-white solid powder
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
|
| Heavy Atom Count |
37
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| Complexity |
758
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O1C2C=CC(=CC=2C=C1[C@@H](C1C(C)=NOC=1C)O)CC(N[C@@H](C1C=CC=CC=1)C1C=CC(C)=CC=1C)=O
|
| InChi Key |
DIURRJOJDQOMFC-CONSDPRKSA-N
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| InChi Code |
InChI=1S/C31H30N2O4/c1-18-10-12-25(19(2)14-18)30(23-8-6-5-7-9-23)32-28(34)16-22-11-13-26-24(15-22)17-27(36-26)31(35)29-20(3)33-37-21(29)4/h5-15,17,30-31,35H,16H2,1-4H3,(H,32,34)/t30-,31-/m0/s1
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| Chemical Name |
2-[2-[(R)-(3,5-dimethyl-1,2-oxazol-4-yl)-hydroxymethyl]-1-benzofuran-5-yl]-N-[(S)-(2,4-dimethylphenyl)-phenylmethyl]acetamide
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| Synonyms |
TMP780; TMP780; 1422053-03-9; 2-(2-((R)-(3,5-Dimethylisoxazol-4-yl)(hydroxy)methyl)benzofuran-5-yl)-N-((S)-(2,4-dimethylphenyl)(phenyl)methyl)acetamide; 2-[2-[(R)-(3,5-dimethyl-1,2-oxazol-4-yl)-hydroxymethyl]-1-benzofuran-5-yl]-N-[(S)-(2,4-dimethylphenyl)-phenylmethyl]acetamide; 1422171-08-1; TMP-780
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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 |
| 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 : ~220 mg/mL (~444.82 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5.5 mg/mL (11.12 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 55.0 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: ≥ 5.5 mg/mL (11.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 55.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0219 mL | 10.1096 mL | 20.2192 mL | |
| 5 mM | 0.4044 mL | 2.0219 mL | 4.0438 mL | |
| 10 mM | 0.2022 mL | 1.0110 mL | 2.0219 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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