| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Vimirogant (formerly VTP-43742; AGN-242428; VTP43742; AGN242428) is a novel, orally bioactive and potent RORγt inhibitor with immunomodulatory activities and has the potential to be used for the treatment of autoimmune disorders such as MS (multiple sclerosis) and psoriasis. It inhibits RORγt with a Ki of 35 nM an an IC50 of 17 nM, and shows >1000-fold selectivity over RORα and RORβ isoforms.
| Targets |
Retinoic acid receptor-related orphan receptor γt (RORγt)
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|---|---|
| ln Vitro |
Human whole blood (IC50=192 nM) and activated hPBMC (IC50=18 nM) both exhibit inhibited IL-17A release when exposed to fumirogant[1].
Vimirogant is a highly potent and selective RORγt inhibitor, exhibiting >1000-fold selectivity over the RORα and RORβ isoforms. It inhibits Th17 cell differentiation and IL-17A secretion from mouse splenocytes with an IC₅₀ of 57 nM, while it does not affect the differentiation of Th1, Th2, or Treg cells. It inhibits IL-17A secretion from activated human peripheral blood mononuclear cells (hPBMCs) with an IC₅₀ of 18 nM. It inhibits IL-17A secretion in human whole blood with an IC₅₀ of 192 nM. |
| ln Vivo |
Vimirogant (po) dramatically decreased clinical symptoms, demyelination, and the mRNA expression of several inflammatory markers in the spinal cord of the MOG35-55/CFA-immunized mouse EAE model [1].
In a mouse experimental autoimmune encephalomyelitis (EAE) model induced by MOG₃₅₋₅₅/CFA immunization, oral administration of Vimirogant significantly suppressed clinical symptoms [1]. The treatment also reduced demyelination and decreased the mRNA expression of multiple inflammatory markers in the spinal cord [1]. |
| Animal Protocol |
Mouse EAE Model: In a study using an experimental autoimmune encephalomyelitis (EAE) mouse model induced by MOG₃₅₋₅₅/CFA immunization, Vimirogant was administered orally. The treatment resulted in a significant reduction of clinical symptoms, demyelination, and inflammatory marker mRNA expression in the spinal cord [1].
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| ADME/Pharmacokinetics |
In a single ascending dose (SAD) study in healthy volunteers (doses ranging from 30 to 2000 mg), Vimirogant demonstrated a terminal plasma half-life of approximately 30 hours.
In the same study, dose proportionality was demonstrated across all dose levels. |
| Toxicity/Toxicokinetics |
In Phase I clinical trials (single and multiple ascending dose studies in healthy volunteers), Vimirogant was reported to be safe and generally well tolerated at all dose levels tested.
No serious adverse events were reported, and all study subjects completed dosing [6]. No clinically significant abnormalities in clinical chemistry, hematology, or electrocardiogram (ECG) were observed. According to a Material Safety Data Sheet (MSDS), the substance is not classified as a hazardous substance or mixture under standard criteria [3]. However, standard laboratory safety precautions (e.g., use of personal protective equipment) are advised. |
| References |
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| Additional Infomation |
Vimirogant (VTP-43742) is an orally active RORγt inhibitor developed for the treatment of autoimmune disorders such as psoriasis and multiple sclerosis.
Its mechanism of action involves the inhibition of IL-17A production and the down-regulation of the IL-23 receptor. In an ex vivo whole blood assay from healthy volunteers in a Phase I trial, Vimirogant suppressed RORγt-dependent IL-17A secretion in a dose-responsive manner. At higher doses, >90% inhibition was observed, which was mostly maintained over 24 hours. In a multiple ascending dose (MAD) study, participants receiving Vimirogant showed >90% inhibition of RORγt-dependent IL-17A secretion in the whole blood assay for a full 24 hours, except in the lowest dose cohort. |
| Molecular Formula |
C27H35F3N4O3S
|
|---|---|
| Molecular Weight |
552.6520
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| Exact Mass |
552.238
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| CAS # |
1802706-04-2
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| Related CAS # |
Vimirogant hydrochloride;1802678-42-7;
2115761-82-3 (2HBr)
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| PubChem CID |
91826726
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| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.3±0.1 g/cm3
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| Boiling Point |
659.4±55.0 °C at 760 mmHg
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| Flash Point |
352.6±31.5 °C
|
| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
| Index of Refraction |
1.541
|
| LogP |
2.54
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
38
|
| Complexity |
902
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
S(C([H])([H])C([H])([H])[H])(C1=C([H])N=C(C([H])=C1[H])C([H])([H])N([H])C(C1C([H])=NC2=C(C=1[H])C([H])([H])N([C@@]2([H])C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])C1([H])C([H])([H])C([H])([H])C([H])(C(F)(F)F)C([H])([H])C1([H])[H])=O)(=O)=O
|
| InChi Key |
XUYMIRYNRKXKOR-JUWHTYBZSA-N
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| InChi Code |
InChI=1S/C27H35F3N4O3S/c1-4-38(36,37)23-10-9-22(31-14-23)13-33-26(35)19-11-20-16-34(25(17(2)3)24(20)32-12-19)15-18-5-7-21(8-6-18)27(28,29)30/h9-12,14,17-18,21,25H,4-8,13,15-16H2,1-3H3,(H,33,35)/t18?,21?,25-/m0/s1
|
| Chemical Name |
(7S)-N-[(5-ethylsulfonylpyridin-2-yl)methyl]-7-propan-2-yl-6-[[4-(trifluoromethyl)cyclohexyl]methyl]-5,7-dihydropyrrolo[3,4-b]pyridine-3-carboxamide
|
| Synonyms |
VTP-43742; AGN-242428; VTP 43742; AGN242428; VTP43742; AGN 242428.
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.8095 mL | 9.0473 mL | 18.0946 mL | |
| 5 mM | 0.3619 mL | 1.8095 mL | 3.6189 mL | |
| 10 mM | 0.1809 mL | 0.9047 mL | 1.8095 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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