LGD-3303 917891-35-1_Others_Signaling Pathways_Products

LGD-3303 is a potent, selective, orally bioavailable, and non-sterdoidal androgen receptor modulator (SARM) with anabolic effects on muscle and cortical bone not observed with bisphosphonates. It shows little or no cross-reactivity with related nuclear receptors. Upon oral administration of LGD-3303 for 14 days in orchidectomized male rats, the tissue selective activity of LGD-3303 was assessed, and LGD-3303 was found to increase the levator ani muscle weight above eugonadal levels but had greatly reduced activity on the prostate, never increasing the ventral prostate weight to >50% of eugonadal levels even at high doses.LGD-3303 increased muscle weight in females rats. In addition, LGD-3303 increased BMD and BMC at both cortical and cancellous bone sites. At cortical sites, the effects were caused in part by anabolic activity on the periosteal surface.

Physicochemical Properties

Molecular Formula

C16H14CLF3N2O

Molecular Weight

342.75

Exact Mass

342.075

CAS #

917891-35-1

Related CAS #

917891-35-1

PubChem CID

25195253

Appearance

Light yellow to yellow solid powder

LogP

4.569

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

522

Defined Atom Stereocenter Count

SMILES

O=C1NC2C=CC3N(CC(F)(F)F)C(CC)=C(C)C=3C=2C(Cl)=C1

InChi Key

OMXGOGXEWUCLFI-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H14ClF3N2O/c1-3-11-8(2)14-12(22(11)7-16(18,19)20)5-4-10-15(14)9(17)6-13(23)21-10/h4-6H,3,7H2,1-2H3,(H,21,23)

Chemical Name

9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo(3,2-F)quinolin-7(6H)-one

Synonyms

LGD-3303; LGD3303; LGD 3303

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)

Biological Activity

ln Vitro

In vitro activity: LGD‐3303 is a nonsteroidal, nonaromatizable androgen receptor ligand that binds to the androgen receptor with high affinity in a radiolabeled to competitive binding assay (Ki = 0.9 nM). LGD‐3303 binds to the mineralocorticoid, glucocorticoid, and progesterone receptors with greatly reduced affinity in comparison with the androgen receptor (Ki = 1261, 581, and 136 nM, respectively). LGD‐3303 potently activates transcription through the androgen receptor (EC50 = 3.6 nM) and has 134% efficacy relative to the steroidal androgen DHT. LGD‐3303 has minimal activity on other related nuclear hormone receptors in a transcriptional activity assay. Maximal efficacy relative to the natural ligands was determined to be 10% for the mineralocorticoid receptor, 1% for the glucocorticoid receptor, 1% for the estrogen receptor α, and 38% for the progesterone receptor. Potency could only be determined for the mineralocorticoid receptor (EC50 = 3695 nM) and the progesterone receptor (EC50 = 2233 nM).

Kinase Assay: LGD‐3303 is a nonsteroidal, nonaromatizable androgen receptor ligand that binds to the androgen receptor with high affinity in a radiolabeled to competitive binding assay (Ki = 0.9 nM). LGD‐3303 binds to the mineralocorticoid, glucocorticoid, and progesterone receptors with greatly reduced affinity in comparison with the androgen receptor (Ki = 1261, 581, and 136 nM, respectively). LGD‐3303 potently activates transcription through the androgen receptor (EC50 = 3.6 nM) and has 134% efficacy relative to the steroidal androgen DHT.

Cell Assay: Data were collected at 10 Hz from the load cell and the cross‐head displacement and analyzed using software designed for materials testing (TestWorks 4; MTS). Whole femurs were tested to failure in three‐point bending, and the fifth lumbar vertebral body was tested to failure in compression after removal of the endplates and spinous processes. The preparation and testing of the vertebral body have been previously described. Maximum load, stiffness, and energy absorption were measured from the load‐deformation curve for each specimen. Elastic modulus, maximum stress, and toughness were calculated based on standard engineering equations for three‐point bending or compression testing, respectively.

ln Vivo

Both testosterone propionate and LGD‐3303 had anabolic activity in muscle in ORDX male rats, significantly increasing the levator ani weight in a dose‐dependent manner. Histological examination was not performed in this experiment; however, examination of H&E‐stained skeletal muscle sections in other studies showed no abnormal histological findings at doses of LGD‐3303 up to 450 mg/kg, suggesting normal muscle physiology (unpublished data). LGD‐3303 and testosterone displayed similar potency, maintaining the levator ani near eugonadal levels with a 1‐mg/kg dose. Testosterone stimulated the ventral prostate to 50% of eugonadal levels with the 1‐mg/kg dose and exceeded the eugonadal level with the 3‐mg/kg dose, indicating minimal tissue selective activity. LGD‐3303, however, had negligible activity on the ventral prostate at 1 mg/kg (<5% efficacy). At higher doses of LGD‐3303, the ventral prostate weight never reached the eugonadal level, restoring the ventral prostate to <50% of eugonadal levels at 100 mg/kg. The finding that prostate weight is maximally stimulated by LGD‐3303 to a level markedly less than testosterone, a full agonist, indicates that this compound is a partial agonist on the prostate. This partial agonist activity on the prostate occurred despite increasing plasma concentrations of compound (data not shown).

Animal Protocol

Suspended in Tween 80, polyethylene glycol-400, and 0.1% carboxy-methyl cellulose in water (0.005%:10%:89.995%); oral administration

ORDX male rats

References

J Bone Miner Res.2009 Feb;24(2):231-40.

Additional Infomation

An androgen receptor modulator.

Solubility Data

Solubility (In Vitro)

DMSO: >10 mM

Water:<1 mg/mL

Ethanol:

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
(e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).
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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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).
Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9176 mL	14.5879 mL	29.1758 mL
	5 mM	0.5835 mL	2.9176 mL	5.8352 mL
	10 mM	0.2918 mL	1.4588 mL	2.9176 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.

PeptideDB

LGD-3303 917891-35-1

CAS No.: 917891-35-1

Physicochemical Properties

Biological Activity

Solubility Data