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Purity: ≥98%
TTNPB (AGN-191183; Ro 13 7410; AGN 191183; Arotinoid Acid, Ro13-7410, AGN191183) is a potent RAR (retinoic acid receptor) agonist with potential antitumor activity. It inhibits the binding of [3H]tRA to human RARα, β, and γ with IC50s of 5.1 nM, 4.5 nM, and 9.3 nM, respectively. TTNPB inhibits chondrogenesis with IC50 value of 0.14nM when using mouse limb bud cell cultures. The action of TTNPB results from binding to nuclear receptors. TTNPB can competes with [3H]tRA and prevent them from binding to mRARα, mRARβ and mRARγ with IC50 values of 3.8nM, 4nM and 4.5nM, respectively.
| Targets |
RARα (IC50 = 5.1 nM); RARβ(IC50 = 4.5 nM); RARγ (IC50 = 9.3 nM)
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| ln Vitro |
For human RARα, β, and γ, TTNPB has IC50s of 3.8 nM, 4 nM, and 4.5 nM, respectively, which inhibits [3H]tRA binding. TTNPB, whose IC50 is 1800 nM, competes with CRABPI for the binding of [3H]tRA [1].
The aromatic retinoid (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1 -propenyl] benzoic acid (TTNPB) is 1000-fold more potent as a teratogen than all trans-retinoic acid (tRA) in several species and in the inhibition of chondrogenesis in the mouse limb bud cell culture. Factors responsible for the potency of TTNPB were investigated including binding to nuclear retinoic acid receptors (RARs and RXRs), cytosolic binding proteins (CRABPs), and metabolic disposition of TTNPB. For competitive binding assays and saturation kinetics, nucleosol or cytosol fractions were obtained from COS-1 cells transfected with cDNAs encoding the appropriate nuclear receptor or binding protein. TTNPB binds to RAR alpha, beta, and gamma with Kds in the nanomolar range; however, these binding affinities are 10-fold less than those of tRA. Although the affinities are high for TTNPB, it is unlikely that the binding affinities to nuclear receptors alone account for the potency of TTNPB. The binding affinities of TTNPB for the CRABPs are significantly lower than those of tRA. TTNPB did not compete with [3H]9-cis RA for binding to RXR alpha, beta, or gamma. Mouse limb bud cell cultures, a well characterized model for retinoid teratogenesis, were used to compare the metabolic disposition of TTNPB and tRA. In the media of limb bud cell cultures treated with either retinoid, the disappearance of TTNPB was significantly slower than that of tRA over 72 hr. Both retinoids reached approximately equal concentrations in cell uptake experiments; however, TTNPB disappeared from the limb bud cell at a significantly slower rate than did tRA. Collectively, these results indicate that high affinity binding to RARs, lower affinity to CRABPs, and resistance to metabolism contribute to the potency of TTNPB [1]. |
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| ln Vivo |
Hyaline cartilage tissue is formed in vivo when TTNPB (Ro 13-7410) (GMP) (100 nM) and Laduviglusib are combined [2].
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| Enzyme Assay |
Labeled and unlabeled retinoids were added to nucleosol or cytosolic fractions in ethanol so that the total amount of ethanol added was constant in all tubes and did not exceed 2% of the incubation volume. The receptor preparations were incubated with retinoids at 47°C for 4-6 hr. Sephadex PD-10 desalting columns were used to separate bound radioligand from free radioligand after equilibrium was achieved. For competitive binding assays, varying concentrations of unlabeled competing ligand were incubated with the appropriate nucleosol or cytosol in the presence of a fixed concentration of [3H]tRA (sp act. 49.3 Ci/mmol) or [3H]9-cis RA (sp. act. 24.0 Ci/mmol). Final concentrations of [3H] tRA and [3H]9-cis RA for nuclear receptor binding assays were 5nM. Final concentrations of [3H]tRA for CRABP binding assays was 30 nM. The IC50s were calculated. For saturation kinetics, increasing concentrations of radiolabeled ligand ([3H]tRA sp. act. 49.3 Ci/mmol, [3H]TTNPB sp. act. 5.5 Ci/mmol) were added to the nucleosol of the appropriate receptor subtype in the presence (nonspecific binding) or absence (total binding) of a 100-fold molar excess of the corresponding unlabeled retinoid. Specific binding wass defined as the total binding minus nonspecific binding. Saturation kinetics were calculated[1].
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| References | |||
| Additional Infomation |
Arotinoid acid is a retinoid that consists of benzoic acid substituted at position 4 by a 2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)prop-1-en-1-yl group. It is a synthetic retinoid that acts as a selective agonist for the retinoic acid receptors (RAR). It has a role as an antineoplastic agent, a retinoic acid receptor agonist and a teratogenic agent. It is a member of benzoic acids, a retinoid and a member of naphthalenes.
Arotinoid acid is a retinoic acid analog which acts as a selective RAR agonist. |
| Molecular Formula |
C24H28O2
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| Molecular Weight |
348.48
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| Exact Mass |
348.208
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| Elemental Analysis |
C, 82.72; H, 8.10; O, 9.18
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| CAS # |
71441-28-6
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| Related CAS # |
TTNPB;71441-28-6
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| PubChem CID |
5289501
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
486.8±44.0 °C at 760 mmHg
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| Melting Point |
240-241 °C
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| Flash Point |
228.6±23.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.579
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| LogP |
8.62
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
549
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C/C(=C\C1=CC=C(C=C1)C(=O)O)/C2=CC3=C(C=C2)C(CCC3(C)C)(C)C
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| InChi Key |
FOIVPCKZDPCJJY-JQIJEIRASA-N
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| InChi Code |
InChI=1S/C24H28O2/c1-16(14-17-6-8-18(9-7-17)22(25)26)19-10-11-20-21(15-19)24(4,5)13-12-23(20,2)3/h6-11,14-15H,12-13H2,1-5H3,(H,25,26)/b16-14+
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| Chemical Name |
4-[(E)-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]benzoic acid
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| Synonyms |
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (3.59 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8696 mL | 14.3480 mL | 28.6961 mL | |
| 5 mM | 0.5739 mL | 2.8696 mL | 5.7392 mL | |
| 10 mM | 0.2870 mL | 1.4348 mL | 2.8696 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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