Bexarotene | LGD1069 | CAS#153559-49-0 | retinoid X receptor

MedKoo Cat#: 100080 | Name: Bexarotene

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Bexarotene, also known as LGD-1069, is a synthetic retinoic acid agent with potential antineoplastic, chemopreventive, teratogenic and embryotoxic properties. Bexarotene selectively binds to and activates retinoid X receptors (RXRs), thereby inducing changes in gene expression that lead to cell differentiation, decreased cell proliferation, apoptosis of some cancer cell types, and tumor regression.

Chemical Structure

Bexarotene

CAS#153559-49-0

Theoretical Analysis

MedKoo Cat#: 100080

Name: Bexarotene

CAS#: 153559-49-0

Chemical Formula: C24H28O2

Exact Mass: 348.2089

Molecular Weight: 348.48

Elemental Analysis: C, 82.72; H, 8.10; O, 9.18

Price and Availability

Size	Price	Availability
100mg	USD 90.00	Ready to ship
200mg	USD 150.00	Ready to ship
500mg	USD 250.00	Ready to ship
1g	USD 450.00	Ready to ship
2g	USD 650.00	Ready to ship
5g	USD 1,150.00	Ready to ship
10g	USD 1,950.00	Ready to ship
20g	USD 3,450.00	2 weeks

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Related CAS #

No Data

Synonym

LGD1069; LGD 1069; LGD-1069; LG 100069; Ro 26-445; SR 11247; 3-methyl TTNEB. Bexarotene; US brand name: Targretin.

IUPAC/Chemical Name

4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid

InChi Key

NAVMQTYZDKMPEU-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H28O2/c1-15-13-20-21(24(5,6)12-11-23(20,3)4)14-19(15)16(2)17-7-9-18(10-8-17)22(25)26/h7-10,13-14H,2,11-12H2,1,3-6H3,(H,25,26)

SMILES Code

O=C(O)C1=CC=C(C(C2=C(C)C=C3C(C)(C)CCC(C)(C)C3=C2)=C)C=C1

Appearance

Off-white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Bexarotene (Targretin) is an oral antineoplastic agent indicated by the FDA (in 2000) for cutaneous T cell lymphoma. It has been used off-label for lung cancer, breast cancer, and Kaposi's sarcoma. Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy (oral) and for the topical treatment of cutaneous lesions in patients with CTCL (Stage IA and IB) who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical). Bexarotene is an off-white to white powder with a molecular weight of 348.48 and a molecular formula of C24H28O2. It is insoluble in water and slightly soluble in vegetable oils and ethanol, USP. Each TargretinÂ® (bexarotene) capsule also contains the following inactive ingredients: polyethylene glycol 400, NF, polysorbate 20, NF, povidone, USP, and butylated hydroxyanisole, NF. The capsule shell contains gelatin, NF, sorbitol special-glycerin blend, and titanium dioxide, USP. Mechanism of Action: Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models. The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown. Mechanism of Action: Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models. The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC50513

QC Data

View QC data: current batch, Lot#TZC50513

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Bexarotene (LGD1069) is a selective retinoid X receptors (RXR) agonist for the treatment of cutaneous T-cell lymphoma.

In vitro activity:

Since CD163+ TAMs produced CCL22 in the lesional skin of MF, it was hypothesized that bexarotene might decrease the production of CCL22 from CD163+ M2 macrophages. To test this, this study evaluated the production of chemokines from CD163+ M2 macrophages using M2 macrophages generated from peripheral blood mononuclear cells (PBMCs) in healthy donors. Production of CCL22 was significantly decreased by bexarotene in a dose-dependent manner (Figure 5A). The purity of cultured CD163+ M2 macrophages is >90% as assessed by FACS analysis (Figure 5B). Reference: Front Oncol. 2019; 9: 907. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763730/

In vivo activity:

Mice were subjected to ICH induction by autologous injection of fluorescently-labelled erythrocytes followed by bexarotene or vehicle treatment beginning at 3 hours and continuing daily. At day 3 after ICH, the MDMs from the perihematomal brains were analyzed by flow cytometry for phagocytosis of labelled erythrocytes. Treatment with bexarotene resulted in increased MDM phagocytosis of erythrocytes compared to the vehicle-treated mice (41.9 ± 5.6 % vs. 24.7 ± 10.0 % positive MDMs, p<0.05; Figure 2A). Consistent with the flow cytometry results, bexarotene administration reduced hematoma volume compared with that of vehicle-treated mice on day 3 post-ICH (2.9 ± 0.7 mm3 vs. 1.4 ± 0.6 mm3 of hematoma; Figure 2B). Additionally, bexarotene-treated mice exhibited better functional performance on the cylinder test on day 3 after ICH (Figure 2C). Reference: Stroke. 2020 Feb; 51(2): 612–618. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135897/

	Solvent	mg/mL	mM
Solubility
	DMSO	43.5	124.71
	DMF	20.0	57.39
	DMF:PBS (pH 7.2) (1:3)	0.3	0.72
	Ethanol	3.7	10.73

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 348.48 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Kamp F, Scheidt HA, Winkler E, Basset G, Heinel H, Hutchison JM, LaPointe LM, Sanders CR, Steiner H, Huster D. Bexarotene Binds to the Amyloid Precursor Protein Transmembrane Domain, Alters Its α-Helical Conformation, and Inhibits γ-Secretase Nonselectively in Liposomes. ACS Chem Neurosci. 2018 Jul 18;9(7):1702-1713. doi: 10.1021/acschemneuro.8b00068. Epub 2018 May 11. PMID: 29717863; PMCID: PMC6051911. 2. Tanita K, Fujimura T, Sato Y, Lyu C, Kambayashi Y, Ogata D, Fukushima S, Miyashita A, Nakajima H, Nakamura M, Morita A, Aiba S. Bexarotene Reduces Production of CCL22 From Tumor-Associated Macrophages in Cutaneous T-Cell Lymphoma. Front Oncol. 2019 Sep 20;9:907. doi: 10.3389/fonc.2019.00907. PMID: 31616630; PMCID: PMC6763730. 3. Chang CF, Massey J, Osherov A, Angenendt da Costa LH, Sansing LH. Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage. Stroke. 2020 Feb;51(2):612-618. doi: 10.1161/STROKEAHA.119.027037. Epub 2019 Dec 12. PMID: 31826730; PMCID: PMC7135897.v 4. Huuskonen MT, Loppi S, Dhungana H, Keksa-Goldsteine V, Lemarchant S, Korhonen P, Wojciechowski S, Pollari E, Valonen P, Koponen J, Takashima A, Landreth G, Goldsteins G, Malm T, Koistinaho J, Kanninen KM. Bexarotene targets autophagy and is protective against thromboembolic stroke in aged mice with tauopathy. Sci Rep. 2016 Sep 14;6:33176. doi: 10.1038/srep33176. PMID: 27624652; PMCID: PMC5021977.

In vitro protocol:

In vivo protocol:

1. Chang CF, Massey J, Osherov A, Angenendt da Costa LH, Sansing LH. Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage. Stroke. 2020 Feb;51(2):612-618. doi: 10.1161/STROKEAHA.119.027037. Epub 2019 Dec 12. PMID: 31826730; PMCID: PMC7135897.v 2. Huuskonen MT, Loppi S, Dhungana H, Keksa-Goldsteine V, Lemarchant S, Korhonen P, Wojciechowski S, Pollari E, Valonen P, Koponen J, Takashima A, Landreth G, Goldsteins G, Malm T, Koistinaho J, Kanninen KM. Bexarotene targets autophagy and is protective against thromboembolic stroke in aged mice with tauopathy. Sci Rep. 2016 Sep 14;6:33176. doi: 10.1038/srep33176. PMID: 27624652; PMCID: PMC5021977.

1: Chang CF, Massey J, Osherov A, Angenendt da Costa LH, Sansing LH. Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage. Stroke. 2020 Feb;51(2):612-618. doi: 10.1161/STROKEAHA.119.027037. Epub 2019 Dec 12. PMID: 31826730; PMCID: PMC7135897. 2: Lowe MN, Plosker GL. Bexarotene. Am J Clin Dermatol. 2000 Jul- Aug;1(4):245-50; discussion 251-2. doi: 10.2165/00128071-200001040-00006. PMID: 11702369. 3: Bexarotene. Am J Health Syst Pharm. 2000 Dec 1;57(23):2167. doi: 10.1093/ajhp/57.23.2167. PMID: 11127695. 4: Farol LT, Hymes KB. Bexarotene: a clinical review. Expert Rev Anticancer Ther. 2004 Apr;4(2):180-8. doi: 10.1586/14737140.4.2.180. PMID: 15056048. 5: Qu L, Tang X. Bexarotene: a promising anticancer agent. Cancer Chemother Pharmacol. 2010 Jan;65(2):201-5. doi: 10.1007/s00280-009-1140-4. Epub 2009 Sep 24. PMID: 19777233. 6: Wong SF. Oral bexarotene in the treatment of cutaneous T-cell lymphoma. Ann Pharmacother. 2001 Sep;35(9):1056-65. doi: 10.1177/106002800103500903. PMID: 11573857. 7: Shen D, Yu X, Wu Y, Chen Y, Li G, Cheng F, Xia L. Emerging roles of bexarotene in the prevention, treatment and anti-drug resistance of cancers. Expert Rev Anticancer Ther. 2018 May;18(5):487-499. doi: 10.1080/14737140.2018.1449648. Epub 2018 Mar 20. PMID: 29521139. 8: Kobayashi T, Mitsuhashi A, Hongying P, Shioya M, Kojima K, Nishikimi K, Yahiro K, Shozu M. Bexarotene-induced cell death in ovarian cancer cells through Caspase-4-gasdermin E mediated pyroptosis. Sci Rep. 2022 Jul 1;12(1):11123. doi: 10.1038/s41598-022-15348-7. PMID: 35778597; PMCID: PMC9249775. 9: Wang W, Lu Z, Wang M, Liu Z, Wu B, Yang C, Huan H, Gong P. The cuproptosis- related signature associated with the tumor environment and prognosis of patients with glioma. Front Immunol. 2022 Aug 30;13:998236. doi: 10.3389/fimmu.2022.998236. PMID: 36110851; PMCID: PMC9468372. 10: Hurst RE. Bexarotene ligand pharmaceuticals. Curr Opin Investig Drugs. 2000 Dec;1(4):514-23. PMID: 11249708. 11: Martin AG. Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas. J Drugs Dermatol. 2003 Apr;2(2):155-67. PMID: 12852367. 12: Duvic M. Bexarotene and DAB(389)IL-2 (denileukin diftitox, ONTAK) in treatment of cutaneous T-cell lymphomas: algorithms. Clin Lymphoma. 2000 Nov;1 Suppl 1:S51-5. doi: 10.3816/clm.2000.s.010. PMID: 11707865. 13: Beylot-Barry M. Bexarotène: targretin [Bexarotene: targretin]. Ann Dermatol Venereol. 2007 Dec;134(12):987-91. French. doi: 10.1016/s0151-9638(07)78263-7. PMID: 18166923. 14: Toi N, Kurajoh M, Miyaoka D, Nagata Y, Yamada S, Imanishi Y, Hayashi D, Tateishi C, Inaba M, Tsuruta D, Morita A, Emoto M. Bexarotene-induced central hypothyroidism assessed by TRH stimulation test in cutaneous T-cell lymphoma patients. Endocr J. 2022 Jan 28;69(1):101-105. doi: 10.1507/endocrj.EJ21-0313. Epub 2021 Aug 25. PMID: 34433736. 15: Makita N, Manaka K, Sato J, Mitani K, Nangaku M, Iiri T. Bexarotene-induced hypothyroidism: Characteristics and therapeutic strategies. Clin Endocrinol (Oxf). 2019 Jul;91(1):195-200. doi: 10.1111/cen.13975. Epub 2019 Apr 11. PMID: 30903705. 16: Gniadecki R, Assaf C, Bagot M, Dummer R, Duvic M, Knobler R, Ranki A, Schwandt P, Whittaker S. The optimal use of bexarotene in cutaneous T-cell lymphoma. Br J Dermatol. 2007 Sep;157(3):433-40. doi: 10.1111/j.1365-2133.2007.07975.x. Epub 2007 Jun 6. PMID: 17553039. 17: Qi L, Guo Y, Zhang P, Cao X, Luan Y. Preventive and Therapeutic Effects of the Retinoid X Receptor Agonist Bexarotene on Tumors. Curr Drug Metab. 2016;17(2):118-28. doi: 10.2174/138920021702160114121706. PMID: 26806040. 18: Pileri A, Delfino C, Grandi V, Pimpinelli N. Role of bexarotene in the treatment of cutaneous T-cell lymphoma: the clinical and immunological sides. Immunotherapy. 2013 Apr;5(4):427-33. doi: 10.2217/imt.13.15. PMID: 23557425. 19: Valipour A, Jäger M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3. PMID: 32632956; PMCID: PMC7389258. 20: Sethi TK, Montanari F, Foss F, Reddy N. How we treat advanced stage cutaneous T-cell lymphoma - mycosis fungoides and Sézary syndrome. Br J Haematol. 2021 Nov;195(3):352-364. doi: 10.1111/bjh.17458. Epub 2021 May 14. PMID: 33987825.