MYCi361 (NUCC0196361) is a novel and potent MYC inhibitor (Kd = 3.2 μM) with potential anticancer activity, it demonstrated a narrow therapeutic index. MYCi361 phosphorylated MYC within cells, shattered MYC/MAX dimers, and reduced MYC-stimulated transcription. Additionally, it increased the phosphorylation of MYC on threonine-58, which increased the degradation of MYC by proteasomes. MYCi361 has the ability to improve anti-PD1 immunotherapy and inhibit tumor growth.

Physicochemical Properties

Molecular Formula	C26H16CLF9N2O2
Molecular Weight	594.8561
Exact Mass	594.075
Elemental Analysis	C, 52.50; H, 2.71; Cl, 5.96; F, 28.74; N, 4.71; O, 5.38
CAS #	2289690-31-7
Related CAS #	2289690-31-7;
PubChem CID	139600319
Appearance	White to off-white solid powder
LogP	7.9
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	5
Heavy Atom Count	40
Complexity	813
Defined Atom Stereocenter Count	0
InChi Key	CKLCWLSEYDDTCN-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H16ClF9N2O2/c1-38-19(11-21(37-38)26(34,35)36)18-6-7-20(40-12-13-2-4-17(27)5-3-13)22(23(18)39)14-8-15(24(28,29)30)10-16(9-14)25(31,32)33/h2-11,39H,12H2,1H3
Chemical Name	2-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-chlorophenyl)methoxy]-6-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]phenol
Synonyms	NUCC-0196361; NUCC0196361; NUCC 0196361; MYC i361; MYCi361; MYC-i361
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

Targets	MYC (Kd = 3.2 μM)
ln Vitro	MYCi361 inhibits MYC-driven gene expression, breaks down MYC/MAX dimers, and activates MYC inside of cells. MYCi361 increases MYC phosphorylation on threonine-58, which in turn increases MYC degradation by the proteasome.[1]
ln Vivo	MYCi361 upregulates PD-L1 on tumors, enhances tumor immune cell infiltration, inhibits in vivo tumor growth in mice, and makes tumors more susceptible to anti-PD1 immunotherapy.[1]
Cell Assay	The supernatants are obtained after treating MycCaP cells with 4 μM MYCi361 for a duration of 72 hours. To quantify high mobility group protein B1 (HMGB1) and secreted ATP, cell counts are carried out. After incubating cells with rabbit anti-Calreticulin for 60 minutes, they are subjected to an analysis by flow cytometry using Alexa Flour 488 anti-rabbit secondary antibody to detect the presence of surface Calreticulin.
Animal Protocol	6-8 week old FVB mice, prostate PDX model, NSG mice, C57BL/6 mice, CB17/Icr-Prkdcscid/IcrIcoCrl mice, CD-1 mice 55 mg/kg, 50 mg/kg IP, Oral gavage
References	[1]. Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy. Cancer Cell. 2019 Nov 11;36(5):483-497.e15.

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~168.1 mM) Ethanol: ~14 mg/mL (~23.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6811 mL	8.4053 mL	16.8107 mL
	5 mM	0.3362 mL	1.6811 mL	3.3621 mL
	10 mM	0.1681 mL	0.8405 mL	1.6811 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.