芳维甲酸

TTNPB 是一种有效的 RAR 激动剂。使用人RARs进行竞争性结合实验中,作用于RARα,RARβ和RARγ,IC50 分别为 5.1 nM,4.5 nM 和 9.3 nM。

信号通路 >> 代谢酶/蛋白酶 >> RAR/RXR

研究领域 >> 癌症

IC50: 5.1 nM (RARα), 4.5 nM (RARβ), 9.3 nM (RARγ)[1]

对于人RARα,β和γ,TTNPB分别抑制[3H] tRA与3.8nM,4nM和4.5nM的IC50的结合。 TTNPB竞争[3H] tRA与CRABPI的结合,IC50为1800 nM [1]。

将标记的和未标记的类视黄醇加入乙醇中的核溶质或胞质级分中，使得所有管中加入的乙醇总量恒定，并且不超过培养体积的2％。将受体制剂与类视黄醇在47℃下孵育4-6小时。 Sephadex PD-10脱盐柱用于在达到平衡后将结合的放射性配体与自由放射性配体分离。对于竞争性结合测定，在固定浓度的[3H] tRA（sp act.49.3 Ci / mmol）或[3H] 9-cis RA（sp）存在下，将不同浓度的未标记的竞争配体与适当的核溶胶或胞质溶胶一起孵育。 。动作.24.0 Ci / mmol）。用于核受体结合测定的[3H] tRA和[3H] 9-顺式RA的最终浓度为5nM。 CRABP结合测定的[3H] tRA的最终浓度为30nM。计算IC50。对于饱和动力学，在存在下将增加浓度的放射性标记的配体（[3H] tRA sp。作用49.3Ci / mmol，[3H] TTNPB sp。作用5.5Ci / mmol）加入适当受体亚型的核溶胶中（非特异性结合）或不存在（总结合）100倍摩尔过量的相应未标记的类视黄醇。特异性结合定义为总结合减去非特异性结合。计算饱和动力学[1]。

[1]. Pignatello MA, et al. Multiple factors contribute to the toxicity of the aromatic retinoid, TTNPB (Ro 13-7410): binding affinities and disposition. Toxicol Appl Pharmacol. 1997 Feb;142(2):319-27.

维生素A酸； 视黄酸 | 4-[(5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基)甲酰氨基]苯甲酸 | 他米巴罗汀 | 4-[(1E)-2-[5,6,7,8-四氢-5,5,8,8-四甲基-3-(1H-吡唑-1-基甲基)-2-萘基]乙烯基]苯甲酸 | 芬维A胺 | 厚朴酚 | AGN 194310 | AGN 193109 | CD 437 | 阿达帕林 | AR7 | 他扎罗汀 | UVI 3003 | (R)-氟比洛芬(Tarenflurbil) | AGN 195183

MOLECULAR FORMULA :

C24-H28-O2

MOLECULAR WEIGHT :

348.52

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1040 ug/kg/4D-I

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure) Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 138,169,1996

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1250 ug/kg/25D-I

TOXIC EFFECTS :

Musculoskeletal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :

JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 40,3567,1997

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

125 ug/kg/5D-I

TOXIC EFFECTS :

Endocrine - changes in spleen weight Skin and Appendages - dermatitis, other (after systemic exposure) Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 138,169,1996

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

392 ug/kg/14D-I

TOXIC EFFECTS :

Musculoskeletal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 34,91,1996 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

30 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year: 64,43,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

100 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :

ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year: 64,43,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

37 ug/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 78,533,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

75 ug/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System

REFERENCE :

JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 78,533,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

290 ug/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :

JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 78,533,1987