AC-55649 is a potent, highly isoform-selective agonist of human RARβ2 receptor, with a pEC50 of 6.9.
BMS 753 is an isotype-selective retinoic acid receptor α (RARα) agonist, with a Ki of 2 nM[1].
PA452, retinoic X receptor (RXR) specific antagonist, inhibits the effect of Retinoic acid (RA) on Th1/Th2 development[1].
AGN 196996 is a potent and selective RARα antagonist with Ki value of 2 nM; little binding affinity for RARβ(Ki=1087 nM) and RARγ(Ki=8523 nM).IC50 value: 2 nM(Ki)Target: RARα antagonistAGN 196996 shows no activity in transactivation assays, but instead block the gene transcriptional activity induced by ATRA and other RAR agonists.
Retinoic acid-d6 is the deuterium labeled Retinoic acid[1]. Retinoic acid is a metabolite of vitamin A that plays important roles in cell growth, differentiation, and organogenesis. Retinoic acid is a natural agonist of RAR nuclear receptors, with IC50s of 14 nM for RARα/β/γ. Retinoic acid bind to PPARβ/δ with Kd of 17 nM. Retinoic acid acts as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha[2][3][4][5][6][7].
ER-50891 is a potent antagonist of retinoic acid receptor α(RARα). ER-50891 significantly attenuates ATRA's inhibitive effects on BMP 2-induced osteoblastogenesis[1].
WYC-209, a synthetic retinoid, inhibits proliferation of malignant murine melanoma tumor-repopulating cells (TRCs) with an IC50 of 0.19 μM, has long-term effects and little toxicity, and induces TRCs apoptosis primarily via the caspase 3 pathway. The primary cellular target of WYC-209 is retinoic acid receptor (RAR)[1].
Bexarotene-d3 (LGD1069-d3) is the deuterium labeled Bexarotene. Bexarotene (LGD1069) is a high-affinity and selective retinoid X receptors (RXR) agonist with EC50s of 33, 24, 25 nM for RXRα, RXRβ, and RXRγ, respectively. Bexarotene shows limited affinity for RAR receptors (EC50 >10000 nM). Bexarotene can be used for the research of cutaneous T-cell lymphoma[1][2][3][4].
16α-Hydroxytrametenolic acid, a natural triterpene, is a potential retinoid X receptor (RXR) selective agonist[1].
Tamibarotene is a retinoic acid receptor α/β (RARα/β) agonist, showing high selectivity over RARγ.
AR7 is a retinoic acid receptor α (RARα) antagonist.
Bigelovin, a sesquiterpene lactone isolated from Inula helianthus-aquatica, is a selective retinoid X receptor α agonist. Bigelovin suppresses tumor growth through inducing apoptosis and autophagy via the inhibition of mTOR pathway regulated by ROS generation[1].
Bexarotene is a selective retinoid X receptors (RXR) agonist for the treatment of cutaneous T-cell lymphoma.
BMS453 (BMS-189453), a synthetic retinoid, is a RARβ agonist and a RARα/RARγ antagonist. BMS453 inhibits breast cell growth predominantly through the induction of active TGFβ[1][2].
LG-100064 is a retinoid-X-receptor (RXR) agonist, with EC50s of 330 nM, 200 nM, and 260 nM for RXRα, RXRβ and RXRγ; LG-100064 can be used in the research of cancer.
CD1530 is a selective RARγ agonist with an Kd of 150 nM[1]. CD1530 has been used in combination with bexarotene to inhibit oral carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide in a mouse model of human oral-cavity and esophageal squamous-cell carcinoma[2].
AGN 193109 is a retinoid analog, and acts as a specific and highly effective antagonist of retinoic acid receptors (RARs), with Kds of 2 nM, 2 nM, and 3 nM for RARα, RARβ, and RARγ, respectively.
Isotretinoin(13-cis-Retinoic acid) is a medication used for the treatment of severe acne. It was first developed to be used as a chemotherapy medication for the treatment of brain cancer, pancreatic cancer and more.Target: RAR/RXRIsotretinoin has been the most effective and long-lasting drug for the treatment of severe acne for more than 30 years and can achieve long-term remission in 70-80% of patients after a single course. The new evidence-based European S3-guideline recommends the use of Isotretinoin as a first-line medication for the treatment of severe papulopustular or conglobate acne, especially when prognostically unfavorable factors are present: family history of acne, early onset, marked seborrhea, localization on the trunk, scarring, psychosocial disability or persistent/late-type acne [1]. Five patients with pityriasis rubra pilaris were treated with isotretinoin from September 1982 through 1985. Isotretinoin at an average dose of 1.16 mg/kg/day for 16 to 24 weeks caused complete or almost complete clearing in four of the five patients [2]. isotretinoin produces significant anti-inflammatory effects by inhibition of monocyte and neutrophil chemotaxis across intact biologic barriers in vivo [3]. Isotretinoin 5 mg/day is effective in reducing the number of acne lesions, and improving patients dermatologic quality of life, with minimal adverse effects [4]. Clinical indications: Acne Toxicity: Isotretinoin is teratogenic. It also causes mucocutaneous side effects suck as cheilitis, dry skin, and dry eyes.
LY2955303 is a potent and selective retinoic acid receptor gamma (RARγ) antagonist with a Ki of 1.09 nM.
BMS961 is a selective retinoic acid receptor-γ (RARγ) agonist. BMS961 shows anti-inflammatory activity[1].
4-Hydroxyretinoic acid (4-HRA) is a naturally occurring retinoid derivative with diverse biological effects. 4-Hydroxyretinoic acid is formed from retinol catalyzed by cytochrome P-450 isozyme(s), and is mainly metabolized by the liver in the body. 4-Hydroxyretinoic acid also serves as the substrate for human liver microsomal UDP-glucuronosyltransferase(s) and recombinant UGT2B7. 4-Hydroxyretinoic acid regulates gene expression and cell differentiation via binding to nuclear receptor RAR (Retinoic Acid Receptor), and activates RARs and RXR-alpha, to induce cancer cell apoptosis. In addition, 4-Hydroxyretinoic acid is also involved in various physiological processes such as immune regulation, neuroprotection, and anti-oxidation[1][2].
9-cis-Retinoic acid-d5 (ALRT1057-d5) is the deuterium labeled 9-cis-Retinoic acid. 9-cis-Retinoic acid (ALRT1057), a vitamin A derivative, is a potent RAR/RXR agonist. 9-cis-Retinoic acid induces apoptosis, regulates cell cycle and has anticancer, anti-inflammatory and neuroprotection activities[1][2][3][4][5][6].
Acitretin sodium(Ro 10-1670) is a second-generation, systemic retinoid that has been used in the treatment of psoriasis.Target: RAR/RXRAcitretin sodium is a second-generation, systemic retinoid that has been approved for the treatment of psoriasis since 1997. It can be considered one of the treatments of choice for pustular and erythrodermic psoriasis. However, the efficacy of acitretin sodium as a monotherapy for plaque psoriasis is less, although it is often used in combination therapy with other systemic psoriasis therapies, especially ultraviolet B or psoralen plus ultraviolet A phototherapy, to increase efficacy. Such combination treatments may potentially minimise toxicity by using lower doses of each of the two agent [1].Thirty-nine male adult Wistar albino rats were divided into 3 groups as two experimental groups and one control group. The first group consisting 14 rats were applied orally standard dose (0.75 mg/kg/day) acitretin sodium and the second group consisting 16 rats were applied high dose (1.5 mg/kg/day) acitretin sodium. Acitretin sodium was given within dimetil sulphoxide (DMSO), which was diluted with saline solution as a ratio of 1/10, in order to increase its solubility. The control group consisting 9 rats were given only saline solution including DMSO for 8 weeks. After 8 weeks of the administration, half of the rats in the first and second groups and the entire control group were sacrificed under deep ether anaesthesia and bilateral orchiectomy was made. The remainingrats were compared with the control group using a similar method at the end of 8 weeks of wash-off period. The orchiectomy materials were histopathologically evaluated under the light microscope for spermatogenesis according to parameters including spermatogenetic activity, spermatogenetic organization, seminiferous tubular diameter, interstitial Leydig cells and fibroblasts. In our study it was concluded that the standard and high doses of acitretin sodium do not have any effect on the spermatogenesis of threats [2].Clinical indications: PsoriasisFDA Approved Date: Toxicity: nausea; headache; itching; red or flaky skin; dry or red eyes; dry mouth; depression; hair loss
Adapalene sodium salt(CD 271; Differin), a synthetic retinoid, is a Retinoic acid receptor agonist (RAR).Target: Retinoic acid receptor agonist (RAR)Adapalene sodium salt is a third-generation topical retinoid primarily used in the treatment of mild-moderate acne and is also used (off-label) to treat keratosis pilaris as well as other skin conditions. Adapalene sodium salt is possibly more effective than tretinoin 0.025% gel in the treatment of acne vulgaris [1].Thirty-six rats of either sex were divided into six groups (two control groups, and an etodolac, indomethacin, tretinoin and adapalene sodium salt group) of six animals each. Each group was given different drugs or chemicals. The inhibitory activities of the drugs were determined on carrageenan-induced rat-paw oedema. The inhibition rate (53.48%) in the tretinoin group was found to be higher than adapalene sodium salt and controls (P < 0.05). Adapalene sodium salt was found to have an inhibition rate of 10.28%, and when compared with the other groups, was found to have no statistically significant anti-inflammatory activity [2].Clinical indications: Acne; Purpura; SunburnFDA Approved Date: 1996Toxicity: Skin redness; dryness; itching; scaling; mild burning
XS-060 is a potent anticancer agent and RXRα antagonist. XS-060 significantly induces RXRα-dependent mitotic arrest by inhibiting pRXRα-PLK1 interaction[1].
NBD-125 (B-12), a berberine analogue, is an RXRα activator, with an IC50 of 31.10 μM in KM12C cell[1].
AGN 195183 is a potent and selective agonist of RARα(Kd=3 nM) with improved binding selectivity relative to AGN 193836; no activity on RARβ/γ.IC50 value: 3 nM (Kd); 200 nM (EC80, RAR Trans.)Target: RARα agonistCompound 4(AGN-195183) inhibited the growth of breast cancer cell lines, and was inactive in an in vivo model of topical irritation.Compound 4 and ATRA inhibit growth of the human breast cancer cell lines, T-47D and SK-BR-3, compound 4 does not cause the topical irritation induced by the RARa-selective retinoid, Am-580. Compound 4 (AGN 195183) is currently in Phase I/IIA clinical trials in cancer patients.
HX600 is a synthetic agonist for RXR (Retinoid X Receptor) heterodimer complex. HX600 prevents ischemia-induced neuronal damage. HX600 has orally bioactivity[1].
Fluorobexarotene (compound 20) is a potent retinoid-X-receptor (RXR) agonist, with a Ki value of 12 nM and an EC50 value of 43 nM for RXRα receptor. Fluorobexarotene possesses an apparent RXR binding affinity that is 75% greater than Bexarotene[1].
AGN 205728 is a potent and selective RARγ antagonist with Ki/IC95 values of 3 nM/ 0.6 nM; no inhibiton on RARα and RARβ.IC50 value: 3 nM/ 0.6 nM(Ki/IC95)Target: RARγ antagonistMore information can be found in the following patent, Compound 7a.Preparation of disubstituted chalcone oximes having RARγ retinoid receptor antagonist activityBy Tsang, Kwok Yin; Sinha, Santosh; Liu, Xiaoxia; Bhat, Smita; Chandraratna, Roshantha A.From PCT Int. Appl. (2005), WO 2005066115 A2 20050721.