| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
pEC50: 7.72 (FSHR)[1]
FSHR agonist 1 targets the Follicle-Stimulating Hormone Receptor (FSHR), a G protein-coupled receptor (GPCR). It is a high-affinity, small-molecule allosteric agonist with a pEC50 of 7.72. It forms extensive interactions with the transmembrane domain (TMD) to directly activate FSHR, potentially offering a different signaling profile than the natural ligand. |
|---|---|
| ln Vitro |
Compound 21f, the FSHR agonist, binds to the FSHR TMD pocket and causes TM6 and TM7 to move inward, activating the FSHR directly [1]. Compound 21f, also known as FSHR agonist 1, has the ability to effectively activate FSHR, LHCGR, and TSHR. Notably, the activation potency of FSHR is greater than ten times that of LHCGR (pEC50 of 6.26) and TSHR (pEC50 of 6.48) [1].
FSHR agonist 1 (compound 21f) binds to the TMD pocket of FSHR, inducing inward movement of TM6 and TM7, which leads to direct FSHR activation. It can also activate FSHR, LHCGR, and TSHR, but its activation potency for FSHR is more than 10-fold higher than for LHCGR (pEC50 of 6.26) and TSHR (pEC50 of 6.48). |
| ln Vivo |
By directly activating FSHR, this agonist mimics the effects of FSH in vivo. It is being studied as a potential new approach to enhance fertility treatments. Its oral bioavailability offers a significant advantage over the current injectable FSH therapies, providing a more convenient option for patients with conditions like ovarian insufficiency.
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| Enzyme Assay |
Cell-free FSHR assays are performed using a radioactive GTPgammaS binding assay. Membrane preparations from cells overexpressing FSHR are incubated with [3⁵S]GTPgammaS and varying concentrations of the agonist. The binding of the radiolabeled GTP analog is measured via scintillation counting after filtration, and the pEC50 value is calculated.
|
| Cell Assay |
Chinese hamster ovary (CHO) cells stably expressing the human FSHR and a cAMP-responsive luciferase reporter (CRE-luc) are used. Cells are seeded and treated with a dilution series of FSHR agonist 1 for 4-6 hours. The cells are then lysed, and luciferase activity is measured to quantify receptor activation, as FSHR primarily couples to the Gs protein and increases intracellular cAMP.
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| Animal Protocol |
While specific in vivo data for this agonist is limited, standard protocols for FSHR agonists are conducted in immature female rats (for ovulation studies) or male rats (for spermatogenesis). The agonist is administered as a single oral dose or via injection. Ovarian weight, serum estradiol levels, and number of ovulated oocytes are measured to assess pharmacodynamic activity, providing evidence of the compound's fertility-enhancing potential.
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| ADME/Pharmacokinetics |
FSHR agonist 1 is being developed to overcome the poor oral bioavailability of the natural FSH hormone. As a small-molecule agonist, it is designed for oral administration. Its pharmacokinetic profile is being optimized to achieve sufficient systemic exposure and target engagement in the gonads, aiming for a longer half-life and less frequent dosing compared to injectable FSH.
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| Toxicity/Toxicokinetics |
Toxicological evaluation focuses on safety margins for ovarian hyperstimulation syndrome (OHSS), a risk associated with FSH therapy. Preclinical studies aim to establish that the small-molecule agonist can be dosed safely without inducing supraphysiological responses. The selectivity of the compound for FSHR over LHCGR and TSHR is critical for its safety profile.
|
| References | |
| Additional Infomation |
FSHR agonist 1 is a valuable tool compound for exploring a novel approach to fertility treatment. Unlike the natural FSH protein, small-molecule agonists like this are cheaper to produce and could be formulated as oral pills. This compound is currently in the research and development stage and is not approved for human therapeutic use.
|
| Molecular Formula |
C26H33N3O3S
|
|---|---|
| Molecular Weight |
467.623525381088
|
| Exact Mass |
467.224
|
| CAS # |
1256776-89-2
|
| PubChem CID |
67530240
|
| Appearance |
White to light yellow solid powder
|
| LogP |
4.9
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
33
|
| Complexity |
684
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C12=C(C3SC=CC=3)N=C(C(N(C(C)(C)C)CC)=O)N1CCC1=C2C=C(OC(C)C)C(OC)=C1
|
| InChi Key |
DNSWBPOFBBWYJX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H33N3O3S/c1-8-29(26(4,5)6)25(30)24-27-22(21-10-9-13-33-21)23-18-15-20(32-16(2)3)19(31-7)14-17(18)11-12-28(23)24/h9-10,13-16H,8,11-12H2,1-7H3
|
| Chemical Name |
N-tert-butyl-N-ethyl-8-methoxy-9-propan-2-yloxy-1-thiophen-2-yl-5,6-dihydroimidazo[5,1-a]isoquinoline-3-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 50 mg/mL (106.92 mM)
|
|---|---|
| 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 | 2.1385 mL | 10.6924 mL | 21.3849 mL | |
| 5 mM | 0.4277 mL | 2.1385 mL | 4.2770 mL | |
| 10 mM | 0.2138 mL | 1.0692 mL | 2.1385 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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