MSU-42011 is an orally bioactive retinoid X receptor (RXR) agonist. MSU-42011 can effectively inhibit the expression of iNOS and p-ERK protein levels. MSU-42011 displays immunomodulatory and anti-tumor activity. MSU-42011 may be used in cancer research.

Physicochemical Properties

Molecular Formula	C24H34N2O2
Molecular Weight	382.538966655731
Exact Mass	382.262
CAS #	2456434-36-7
PubChem CID	154656181
Appearance	White to off-white solid powder
LogP	7.1
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	7
Heavy Atom Count	28
Complexity	496
Defined Atom Stereocenter Count	0
InChi Key	VCRGDWUAXDMPKH-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H34N2O2/c1-16(2)15-26(21-10-9-17(14-25-21)22(27)28)20-12-18(23(3,4)5)11-19(13-20)24(6,7)8/h9-14,16H,15H2,1-8H3,(H,27,28)
Chemical Name	6-[3,5-ditert-butyl-N-(2-methylpropyl)anilino]pyridine-3-carboxylic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	MSU-42011 (0-1 μM) has an IC50 value of 158 nM and suppresses iNOS in RAW264.7 macrophage-like cells [1]. In HepG2 cells, MSU-42011 (300 nM; 8 h) exhibits a modest induction of SREBP [1]. In HepG2 cells, MSU-42011 (0-5000 nM; 24 h) activates RXRα [1].
ln Vivo	In the A/J mouse lung cancer model, MSU-42011 (25 mg/kg, PO) dramatically decreased the number, size, and overall burden of tumors. This effect lasted for 12 weeks. Less cells were actively proliferating and the amount of p-ERK was significantly lower than in the control group [1]. Combining MSU-42011 (25 mg/kg; oral; single dosage) with C/P in the A/J mouse lung cancer model resulted in the greatest reduction in tumor number, tumor size, and overall tumor burden. less macrophages in the lungs and more CD8+ T cell activation markers [1]. MSU42011 (PO; single dosage; 100 mg/kg) decreases tumor burden in a lung tumor model in mice [2].
Cell Assay	RT-PCR[1] Cell Types: HepG2 liver cancer cells Tested Concentrations: 300 nM Incubation Duration: 8 h Experimental Results: SREBP expression ranged from no change to a 1.49-fold induction compared to the vehicle control
Animal Protocol	Animal/Disease Models: A/J mice (intraperitoneal (ip)injected with the carcinogen ethyl carbamate (0.32 mg/injection) for 8 weeks)[1] Doses: 25 mg/ kg Route of Administration: Oral administration; One week after, ip every other week for a total of 6 injections with Carboplatin (HY-17393) (50 mg/kg) and paclitaxel (15 mg/kg); for 12 weeks Experimental Results: The number and size of detected lung surface tumors increased not in the treatment group Combines with C/P was most effective in reducing tumor number (67% vs. control), tumor size (76% vs. control), and overall tumor burden (92% vs. . control). Animal/Disease Models: A/J lung cancer model (intraperitoneal (ip)injected with the carcinogen ethyl carbamate (0.32 mg/injection) for 8 weeks)[2] Doses: 100 mg/kg Route of Administration: Oral administration; After 2 weeks, each mouse was intraperitoneally (ip) injected with anti-PD1 and anti-PDL1 antibodies at a rate of 50 μg/mouse, twice a week for a total of 22 times Experimental Results: demonstrated that an increase in the ratio of anti-tumor CD8 T cells to CD4,
References	[1]. The novel rexinoid MSU-42011 is effective for the treatment of preclinical Kras-driven lung cancer. Sci Rep. 2020 Dec 17;10(1):22244. [2]. The RXR Agonist MSU42011 Is Effective for the Treatment of Preclinical HER2+ Breast Cancer and Kras-Driven Lung Cancer. Cancers (Basel). 2021 Oct 6;13(19):5004.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~326.76 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6141 mL	13.0705 mL	26.1411 mL
	5 mM	0.5228 mL	2.6141 mL	5.2282 mL
	10 mM	0.2614 mL	1.3071 mL	2.6141 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.