TTNPB (Arotinoid Acid) is a selective retinoic acid receptor (RAR) agonist. TTNPB competitively binds to RARα (IC50=5.1nM), RARβ (IC50=4.5nM), and RARγ (IC50=9.3nM). TTNPB can be used in research related to cancer development and stem cell differentiation and reprogramming[1-4].
In vitro, Caco-2 cells were treated with TTNPB (0.1-10µM) for 48 hours. TTNPB significantly inhibited UGT2B7 mRNA expression[5]. THP-1 cells were treated with TTNPB (5µM) for 24 or 48 hours. TTNPB significantly upregulated CD36 mRNA and surface protein expression independently of PKC activation[6].
In vivo, TTNPB (0.25mg/kg) was intraperitoneally administered to mice mammary tumor models bearing MXT-HI and MXT-HS from the 7th to the 21st day post-graft (15 administrations total). TTNPB significantly inhibited tumor growth and induced apoptosis[7]. TTNPB (0.072μmol/kg/day) was topically applied to the backs of female hairless mice (Crl:SKH1-hrBR) for 5 consecutive days. TTNPB caused skin desquamation, excoriation, body weight loss, and splenomegaly in mice[8].
References:
[1] Pignatello MA, Kauffman FC, Levin AA. 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.
[2] Pignatello MA, Kauffman FC, Levin AA. Multiple factors contribute to the toxicity of the aromatic retinoid TTNPB (Ro 13-7410): interactions with the retinoic acid receptors. Toxicol Appl Pharmacol. 1999 Sep 1;159(2):109-16.
[3] Nath SC, Babaei-Abraki S, Meng G, et al. A retinoid analogue, TTNPB, promotes clonal expansion of human pluripotent stem cells by upregulating CLDN2 and HoxA1. Commun Biol. 2024 Feb 16;7(1):190.
[4] Hammond LA, Van Krinks CH, Durham J, et al. Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells. Br J Cancer. 2001 Aug 3;85(3):453-62.
[5] Lu Y, Bratton S, Heydel JM, et al. Effect of retinoids on UDP-glucuronosyltransferase 2B7 mRNA expression in Caco-2 cells. Drug Metab Pharmacokinet. 2008;23(5):364-72.
[6] Han S, Sidell N. Peroxisome-proliferator-activated-receptor gamma (PPARgamma) independent induction of CD36 in THP-1 monocytes by retinoic acid. Immunology. 2002 May;106(1):53-9.
[7] Darro F, Cahen P, Vianna A, et al. Growth inhibition of human in vitro and mouse in vitro and in vivo mammary tumor models by retinoids in comparison with tamoxifen and the RU-486 anti-progestagen. Breast Cancer Res Treat. 1998 Sep;51(1):39-55.
[8] Standeven AM, Johnson AT, Escobar M, et al. Specific antagonist of retinoid toxicity in mice. Toxicol Appl Pharmacol. 1996 May;138(1):169-75.