Chromeceptin (94G6) is an inhibitor (blocker/antagonist) of the IGF signaling pathway. Chromeceptin inhibits IGF2 mRNA and protein levels in hepatocytes and HCC cells. Chromeceptin inhibits the phosphorylation levels of AKT and mTOR.

Physicochemical Properties

Molecular Formula	C19H16F3N3O
Molecular Weight	359.3522
Exact Mass	359.125
Elemental Analysis	C, 63.51; H, 4.49; F, 15.86; N, 11.69; O, 4.45
CAS #	331859-86-0
Related CAS #	331859-86-0
PubChem CID	3113922
Appearance	White to light yellow solid powder
LogP	4.689
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	2
Heavy Atom Count	26
Complexity	607
Defined Atom Stereocenter Count	0
SMILES	NC1=C(C#N)C(C2C=CC=C(C(F)(F)F)C=2)C2C=CC(N(C)C)=CC=2O1
InChi Key	GVINXTXGDDSXFQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H16F3N3O/c1-25(2)13-6-7-14-16(9-13)26-18(24)15(10-23)17(14)11-4-3-5-12(8-11)19(20,21)22/h3-9,17H,24H2,1-2H3
Chemical Name	2-amino-7-(dimethylamino)-4-[3-(trifluoromethyl)phenyl]-4H-chromene-3-carbonitrile
Synonyms	94G6; Chromeceptin
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	Chromeceptin (94G6) is described as a synthetic small benzochrome derivative that inhibits the IGF (Insulin-like Growth Factor) signaling pathway in cancer, including hepatocellular carcinoma (HCC). [1]
ln Vitro	Time-blocked inhibition of IGF2 expression in Hep3B TS cells is observed with chromeceptin (94G6) (5 μM) [1]. Rapamycin (mTOR) and protein regulatory B (AKT, Ser463 of AKT, TS cells) are both decreased by chromececeptin. The phosphorylation of the ser371 site in the mTOR effector ribosomal protein S6 rest (p70S6K) is inhibited by chromeceptin [1]. Treatment of Hep3B-derived tumorsphere (TS) cells with Chromeceptin inhibited IGF2 expression in a time-dependent manner. [1] Chromeceptin treatment decreased the number of spheres formed by Hep3B cells in a dose-dependent manner. [1] Chromeceptin treatment decreased the viability of Hep3B-derived TS cells in a dose-dependent manner. [1] In Hep3B-derived TS cells, Chromeceptin treatment decreased the phosphorylation levels of downstream signaling molecules: protein kinase B (AKT at Ser473) and mammalian target of rapamycin (mTOR at Ser2481 and Ser2448). It also repressed phosphorylation at Ser371 in the mTOR effector ribosomal protein S6 kinase (p70S6K). [1] Chromeceptin treatment suppressed the viability of TS cells derived from primary hepatocellular carcinoma cells of four HCC patients. [1]
Cell Assay	Tumorsphere Formation Assay: Hep3B cells were cultured under tumorsphere (TS) culture conditions (in ultra-low attachment dishes with CSC culture medium) to enrich cancer stem cells. The sphere-forming ability was assessed after treatment with different concentrations of Chromeceptin. The number of spheres was enumerated by microscopic examination. [1] Cell Viability Assay: The viability of tumorsphere (TS) cells after Chromeceptin treatment was estimated using a luminescent cell viability assay kit. Luminescence, proportional to the amount of ATP present (an indicator of metabolically active cells), was measured using a multilabel counter. [1] Immunoblot Analysis: Cells (2D adherent or TS cultures) treated with Chromeceptin were lysed. Proteins were resolved by SDS-PAGE, transferred to a membrane, and probed with specific antibodies against target proteins (e.g., IGF2, p-AKT, total AKT, p-mTOR, total mTOR, p-p70S6K). Beta-actin was used as a loading control. Proteins were visualized using enhanced chemiluminescence. This method was used to detect changes in IGF2 expression and phosphorylation status of signaling pathway components. [1]
References	[1]. Loss of miR-100 and miR-125b results in cancer stem cell properties through IGF2 upregulation in hepatocellular carcinoma. Sci Rep. 2020 Dec 8;10(1):21412.
Additional Infomation	Chromeceptin (94G6) is cited as a compound previously reported to suppress IGF2 at both mRNA and protein levels in hepatocyte and HCC cells. [1] In this study, Chromeceptin was used as a pharmacological tool to inhibit the IGF2 pathway. The data suggested that IGF2 plays a role in maintaining cancer stem cell properties and tumorsphere viability through the pAKT and p-mTOR pathway in Hep3B cells. [1]

Solubility Data

Solubility (In Vitro)	DMSO: ~100 mg/mL (~278.3 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 10 mg/mL (27.83 mM) in 50% PEG300 +50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7828 mL	13.9140 mL	27.8280 mL
	5 mM	0.5566 mL	2.7828 mL	5.5656 mL
	10 mM	0.2783 mL	1.3914 mL	2.7828 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.