4-Hydroxyretinoic acid (4-HRA)

4-Hydroxyretinoic acid (4-HRA) is a naturally occurring, primary metabolite derived from all-trans retinoic acid (ATRA) via cytochrome P450 enzyme metabolism^[1]. 4-Hydroxyretinoic acid can bind to retinoic acid receptors (RARs) to regulate gene expression, cell differentiation, and apoptosis, and also serves as a substrate for hepatic microsomal enzymes such as UGT2B7, thereby participating in immune regulation and neuroprotection^[2,3]. 4-Hydroxyretinoic acid is commonly used as a marker of ATRA metabolism to study its conversion activity and regulatory mechanisms, and is also employed in research on acute promyelocytic leukemia and in the treatment of skin conditions such as psoriasis and acne^[4,5,6].

References:
[1] SHIMSHONI J A, ROBERTS A G, SCIAN M, et al. Stereoselective formation and metabolism of 4-hydroxy-retinoic Acid enantiomers by cytochrome p450 enzymes[J]. Journal of Biological Chemistry, 2012, 287(50): 42223-42232.
[2] SAMOKYSZYN V M, GALL W E, ZAWADA G, et al. 4-hydroxyretinoic acid, a novel substrate for human liver microsomal UDP-glucuronosyltransferase (s) and recombinant UGT2B7[J]. Journal of Biological Chemistry, 2000, 275(10): 6908-6914.
[3] DAS B C, THAPA P, KARKI R, et al. Retinoic acid signaling pathways in development and diseases[J]. Bioorganic & Medicinal Chemistry, 2014, 22(2): 673-683.
[4] WANG F, KWAK H S R, ELBULUK N, et al. Retinoic acid 4-hydroxylase inducibility and clinical response to isotretinoin in patients with acne[J]. Journal of the American Academy of Dermatology, 2009, 61(2): 252-258.
[5] ZOUBOULIS C C, VOORHEES J J, ORFANOS C E, et al. Topical all-trans retinoic acid (RA) induces an early, coordinated increase in RA-inducible skin-specific gene/psoriasin and cellular RA-binding protein II mRNA levels which precedes skin erythema[J]. Archives of Dermatological Research, 1996, 288(11): 664-669.
[6] IDRES N, BENOÎT G, FLEXOR M A, et al. Granulocytic differentiation of human NB4 promyelocytic leukemia cells induced by all-trans retinoic acid metabolites[J]. Cancer Research, 2001, 61(2): 700-705.

4-Hydroxyretinoic acid (4-HRA)是一种天然存在的，由全反式视黄酸（ATRA）经细胞色素P450酶代谢生成的主要代谢产物^[1]。4-Hydroxyretinoic acid可结合视黄酸受体（RARs），调控基因表达、细胞分化和凋亡，也是肝脏微粒酶（UGT2B7）的底物，参与免疫调控和神经保护^[2,3]。4-Hydroxyretinoic acid通常作为ATRA代谢的标志物用于研究其转化活性与调控机制，也用于急性原骨髓细胞白血病的研究及皮肤疾病（如银屑病、痤疮）的治疗^[4,5,6]。