| Identification | Back Directory | [Name]
(2E)-3-(4'-Hydroxy-3'-tricyclo[3.3.1.13,7]dec-1-yl[1,1'-biphenyl]-4-yl)-2-propenoic acid | [CAS]
496868-77-0 | [Synonyms]
ST 1926
Adarotene
Adarotene (ST1926)
ST 1926;ST-1926;ST1926
ADAROTENE;ST 1926;ST-1926;ST1926
(E)-3-[4-[3-(1-adamantyl)-4-hydroxyphenyl]phenyl]prop-2-enoic acid
(2E)-3-(4'-Hydroxy-3'-tricyclo[3.3.1.13,7]dec-1-yl[1,1'-biphenyl]-4-yl)-2-propenoic acid
2-Propenoic acid, 3-(4'-hydroxy-3'-tricyclo[3.3.1.13,7]dec-1-yl[1,1'-biphenyl]-4-yl)-, (2E)- | [Molecular Formula]
C25H26O3 | [MOL File]
496868-77-0.mol | [Molecular Weight]
374.47 |
| Chemical Properties | Back Directory | [Melting point ]
>240 °C | [Boiling point ]
574.1±50.0 °C(Predicted) | [density ]
1.257 | [storage temp. ]
Store at -20°C | [solubility ]
≥37.4 mg/mL in DMSO; insoluble in H2O; ≥10.97 mg/mL in EtOH with gentle warming and ultrasonic | [form ]
solid | [pka]
-95.54±0.10(Predicted) | [color ]
White to green | [InChI]
1S/C25H26O3/c26-23-7-6-21(20-4-1-16(2-5-20)3-8-24(27)28)12-22(23)25-13-17-9-18(14-25)11-19(10-17)15-25/h1-8,12,17-19,26H,9-11,13-15H2,(H,27,28)/b8-3+ | [InChIKey]
QAWBIEIZDDIEMW-FPYGCLRLSA-N | [SMILES]
Oc1c(cc(cc1)c5ccc(cc5)\C=C\C(=O)O)C32CC4CC(C3)CC(C2)C4 |
| Safety Data | Back Directory | [WGK Germany ]
WGK 3 | [Storage Class]
11 - Combustible Solids | [Hazard Classifications]
Eye Irrit. 2
Skin Irrit. 2 |
| Hazard Information | Back Directory | [Uses]
Adarotene has been found to have antitumor activity against different types of cancer, including acute myeloid leukemia, primary effusion lymphoma, prostate cancer and glioma. It may also be useful in treating acute lung injury through inflammation and ROS suppression via inactivating TLR4?/NF-?κB and p38?/ERK1?/2 signaling pathways. | [Biological Activity]
ST1926 is an atypical retinoid th at is able to overcome resistance to ATRA. ST1926 appears to induce apoptosis by production of DNA double-strand breaks (DSB) and chromosomal lesions during the S phase of the cell cycle.''ST1926 is considered to be more apoptotic than CD437. It is much effective in mobilizing calcium than CD437. ST1926 repress toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signal pathway to disable the actions of nuclear factor-KB (NF-KB). It has the ability to repress inflammation response and ROS synthesis in lung epithelial cells in vitro. | [Synthesis]
General procedure for the synthesis of (E)-3-(3'-(adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid from methyl (E)-3-(3'-(adamantan-1-yl)-4'-hydroxy-[1,1'-biphenylyl]-4-yl)propenoate: the (E )-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid methyl ester (3.28 g, 8.45 mmol) was added to a solution of LiOH-H2O (1.77 g, 42.25 mmol) in 340 mL of THF/H2O (1:1) and the mixture was stirred at room temperature overnight. After evaporation of THF, the mixture was extracted with hexane, acidified with 2N HCl and filtered to give 2.82 g (94%) of (E)-3-(3'-(adamantan-1-yl)-4'-hydroxy-[1,1'-biphenylyl]-4-yl)propenoic acid with a melting point of > 240 °C. 1H NMR (DMSO-d6): δ 1.74 (6H, s, 6Ad), 2.04 (3H, s, 3Ad), 2.12 (6H, s, 6Ad), 6.51 (1H, d, -CH, J=16.1Hz), 6.85 (1H, d, 1Ar, J=8.8Hz), 7.30-7.40 (2H, m, 2Ar). 7.55-7.63 (3H, m, 2Ar + CH), 7.70 (2H, d, 2Ar, J=8.0Hz), 9.54 (1H, s, -OH), 12.34 (1H, brs, -COOH).MS (m/z): 374 (M+, 100). | [in vivo]
Adarotene (15, 20 mg/kg, p.o.) causes a significant tumor growth inhibition in a human ovarian carcinoma, A2780/DX, and in a human melanoma, MeWo, growing in nude mice[1]. Adarotene (30, 40 mg/kg, p.o.) results in a significant and dose-dependent increase in the life span of NB4-bearing SCID mice without overt toxicity[2]. | [target]
RAR β | [References]
[1] Journal of Medicinal Chemistry, 2003, vol. 46, # 6, p. 909 - 912
[2] Journal of Medicinal Chemistry, 2005, vol. 48, # 15, p. 4931 - 4946
[3] European Journal of Medicinal Chemistry, 2014, vol. 79, p. 251 - 259 |
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