| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Corticotropin-releasing factor receptor type 1 (CRF1, also known as CRHR1). Antalarmin is a non-peptide, high-affinity, and selective antagonist of the CRF1 receptor, which is a GPCR that primarily mediates the endocrine (HPA axis) and behavioral responses to stress.
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|---|---|
| ln Vitro |
Antalarmin is a potent and selective antagonist of the CRF1 receptor, with an IC50 of approximately 2-3 nM for inhibiting CRF-induced cAMP accumulation in cells. It has minimal affinity for the CRF2 receptor or other related GPCRs, demonstrating excellent selectivity. It effectively blocks the actions of CRF in the pituitary and brain.
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| Enzyme Assay |
A cell-free radioligand binding assay is performed using membrane preparations from cells expressing the human CRF1 receptor. The membranes are incubated with [125I]-sauvagine or [125I]-CRF and varying concentrations of antalarmin hydrochloride. After incubation, bound and free ligands are separated by filtration, and radioactivity is counted to calculate the Ki.
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| Cell Assay |
For a functional cellular assay, HEK293 cells stably expressing the human CRF1 receptor are seeded in 96-well plates. Cells are pre-incubated with antalarmin and then stimulated with CRF. After lysis, intracellular cAMP levels are measured using an HTRF or chemiluminescence-based immunoassay to determine the antagonist's IC50 (the concentration needed to block CRF-induced cAMP production).
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| Animal Protocol |
In vivo studies are commonly performed in rats using the "defensive burying" or other stress-induced behavioral tests. Antalarmin can be administered intraperitoneally (i.p.) or orally (p.o.). Endpoints include the amount of time spent burying the shock probe (an index of anxiety-like behavior). Another model is the forced swim test for depression. Brain and plasma levels are taken to correlate exposure with effect.
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| ADME/Pharmacokinetics |
Antalarmin is reported to be orally bioavailable and able to cross the blood-brain barrier. In rats, oral administration achieved significant levels in the brain. This favorable PK property is critical for its use as a central nervous system tool and potential therapeutic.
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| Toxicity/Toxicokinetics |
Not reported for the research compound. However, in the context of drug development, CRF1 antagonists have been generally well-tolerated in human clinical trials, though some have shown liver enzyme elevations. Antalarmin itself was not advanced to Phase III trials.
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| References |
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| Additional Infomation |
Antalarmin was one of the first non-peptide CRF1 antagonists to be developed and was instrumental in validating the CRF1 receptor as a drug target for stress-related disorders. It was originally discovered by scientists at The Scripps Research Institute and later licensed to Pfizer for clinical development. While it showed promise in animal models, clinical trials with other CRF1 antagonists faced challenges, and Antalarmin itself was ultimately not brought to market.
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| Molecular Formula |
C24H35CLN4
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|---|---|
| Molecular Weight |
415.01
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| Exact Mass |
414.255
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| CAS # |
220953-69-5
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| Related CAS # |
Antalarmin;157284-96-3
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| PubChem CID |
16078945
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| Appearance |
White to light yellow solid powder
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| LogP |
6.699
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
485
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCN(CC)C1=NC(=NC2=C1C(=C(N2C3=C(C=C(C=C3C)C)C)C)C)C.Cl
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| InChi Key |
CGDGXEDXEXACKQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H34N4.ClH/c1-9-11-12-27(10-2)23-21-18(6)19(7)28(24(21)26-20(8)25-23)22-16(4)13-15(3)14-17(22)5;/h13-14H,9-12H2,1-8H3;1H
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| Chemical Name |
N-butyl-N-ethyl-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMF: 20 mg/mL (48.19 mM)
Ethanol: 14 mg/mL (33.73 mM) DMSO: 12.5 mg/mL (30.12 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (12.05 mM) in 15% Cremophor EL 85% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4096 mL | 12.0479 mL | 24.0958 mL | |
| 5 mM | 0.4819 mL | 2.4096 mL | 4.8192 mL | |
| 10 mM | 0.2410 mL | 1.2048 mL | 2.4096 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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