| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| Other Sizes |
| Targets |
Ralmitaront targets the trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor that is expressed in brain regions involved in mood, cognition, and reward. TAAR1 is activated by endogenous trace amines such as tyramine, β-phenylethylamine, and tryptamine. Activation of TAAR1 modulates dopaminergic and glutamatergic neurotransmission, which are dysregulated in schizophrenia. Ralmitaront is a partial agonist of TAAR1, meaning it activates the receptor but with less efficacy than a full agonist. This partial agonist activity is thought to provide antipsychotic effects while minimizing the risk of overstimulation and receptor desensitization.
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| ln Vitro |
In vitro, ralmitaront activates TAAR1 with an EC50 of 110.4 nM. The compound's activity at TAAR1 is assessed using cell-based assays measuring receptor activation (e.g., cAMP accumulation, β-arrestin recruitment). Ralmitaront demonstrates partial agonist activity, with less than full efficacy compared to the endogenous agonist. The compound's potency and partial agonist profile contribute to its favorable pharmacological properties. Ralmitaront's selectivity for TAAR1 over other receptors is evaluated to minimize off-target effects.
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| ln Vivo |
In vivo, ralmitaront has demonstrated antipsychotic activity in preclinical models. The compound has been evaluated in animal models of schizophrenia, including those assessing prepulse inhibition, conditioned avoidance response, and phencyclidine-induced hyperactivity. Ralmitaront's efficacy in these models supports its development as a novel antipsychotic agent. The compound is orally active and has been evaluated in clinical trials for schizophrenia. The non-dopaminergic mechanism of action of ralmitaront offers the potential for antipsychotic efficacy without the motor side effects (e.g., extrapyramidal symptoms) and metabolic side effects associated with typical and atypical antipsychotics.
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| Enzyme Assay |
Ralmitaront's activity at TAAR1 is assessed using cell-based functional assays. In these assays, cells expressing TAAR1 are treated with varying concentrations of ralmitaront; receptor activation is measured by cAMP accumulation (using a cAMP detection kit) or by β-arrestin recruitment (using a β-arrestin recruitment assay). EC50 values are calculated from dose-response curves. Selectivity is assessed by screening ralmitaront against a panel of other receptors and ion channels. These assays provide quantitative information on the potency and selectivity of ralmitaront.
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| Cell Assay |
Ralmitaront is tested on cultured cells expressing TAAR1 or other relevant cell types. Cells are treated with varying concentrations of ralmitaront; receptor activation is measured by cAMP accumulation or β-arrestin recruitment; downstream signaling pathways (e.g., ERK, AKT) are assessed by Western blot; neuronal activity is assessed by electrophysiological recordings in neurons expressing TAAR1. These cell-based assays demonstrate the mechanism of action and activity of ralmitaront.
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| Animal Protocol |
Ralmitaront has been evaluated in animal models of schizophrenia and in clinical trials. In preclinical studies, ralmitaront was tested in rodent models of schizophrenia, demonstrating antipsychotic-like activity. The compound has been evaluated in clinical trials for the treatment of schizophrenia and schizoaffective disorder. Ralmitaront's efficacy and safety in patients with schizophrenia have been assessed in Phase 2 clinical trials.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of ralmitaront have been conducted in preclinical species and humans. Ralmitaront is orally active, with good oral bioavailability. The compound's pharmacokinetic profile includes a half-life suitable for once-daily dosing. Ralmitaront is metabolized in the liver and excreted in urine and feces. Pharmacokinetic parameters such as Cmax, Tmax, and half-life have been characterized in clinical studies.
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| Toxicity/Toxicokinetics |
In clinical trials, ralmitaront has been generally well-tolerated. Common adverse effects include headache, nausea, and somnolence. Serious adverse events are uncommon. The safety profile of ralmitaront is consistent with its mechanism of action as a TAAR1 partial agonist. Ralmitaront's lack of dopamine D2 receptor antagonism distinguishes it from conventional antipsychotics and may result in a more favorable side effect profile.
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| References | |
| Additional Infomation |
Drug Indication
Treatment of schizophrenia Ralmitaront (RO6889450, RG-7906) is a potent, orally active partial agonist of TAAR1 being developed for the treatment of schizophrenia and related neuropsychiatric disorders. The compound has an EC50 of 110.4 nM for TAAR1 activation. Ralmitaront represents a novel, non-dopaminergic approach to schizophrenia therapy, offering the potential for antipsychotic efficacy without the side effects associated with dopamine receptor antagonists. The compound has been evaluated in clinical trials for schizophrenia and schizoaffective disorder. Ralmitaront's mechanism of action—modulating dopaminergic and glutamatergic neurotransmission through TAAR1 activation—represents a promising new approach to the treatment of psychiatric disorders. |
| Molecular Formula |
C17H22N4O2
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|---|---|
| Molecular Weight |
314.38
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| Exact Mass |
314.174
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| Elemental Analysis |
C, 64.95; H, 7.05; N, 17.82; O, 10.18
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| CAS # |
2133417-13-5
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| PubChem CID |
130429734
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
491.5±45.0 °C at 760 mmHg
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| Flash Point |
251.0±28.7 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.647
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| LogP |
0.71
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
398
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1C([H])([H])C([H])([H])N([H])C([H])([H])[C@]1([H])C1C([H])=C([H])C(=C([H])C=1[H])N([H])C(C1C(C([H])([H])[H])=C(C([H])([H])C([H])([H])[H])N([H])N=1)=O
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| InChi Key |
XHHXGKRFUPEPFM-OAHLLOKOSA-N
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| InChi Code |
InChI=1S/C17H22N4O2/c1-3-14-11(2)16(21-20-14)17(22)19-13-6-4-12(5-7-13)15-10-18-8-9-23-15/h4-7,15,18H,3,8-10H2,1-2H3,(H,19,22)(H,20,21)/t15-/m1/s1
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| Chemical Name |
5-ethyl-4-methyl-N-[4-[(2S)-morpholin-2-yl]phenyl]-1H-pyrazole-3-carboxamide
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| Synonyms |
Ralmitaront; WHO-11130; RO-6889450; RG-7906; WHO11130; RO6889450; RG7906; WHO 11130; RO 6889450; RG 7906
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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: ~100 mg/mL (~318.1 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 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: ≥ 2.5 mg/mL (7.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1809 mL | 15.9043 mL | 31.8086 mL | |
| 5 mM | 0.6362 mL | 3.1809 mL | 6.3617 mL | |
| 10 mM | 0.3181 mL | 1.5904 mL | 3.1809 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04512066 | Completed | Drug: RO6889450 Drug: Placebo Drug: Risperidone |
Schizophrenia, Schizoaffective Disorder |
Hoffmann-La Roche | September 8, 2020 | Phase 2 |
| NCT02699372 | Completed | Drug: Placebo Drug: RO6889450 |
Healthy Volunteer | Hoffmann-La Roche | March 21, 2016 | Phase 1 |
| NCT03669640 | Terminated | Drug: RO6889450 Drug: Placebo |
Schizophrenia, Schizoaffective Disorder |
Hoffmann-La Roche | December 4, 2018 | Phase 2 |
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