Aryl hydrocarbon receptor (AhR) modifiers as novel cancer therapeutics
Provided herein are novel agents that modulate AhR activity for use in therapeutic compositions and methods thereof for inhibiting cancer cell proliferation and tumor cell invasion and metastasis. The agents comprise AhR inhibitors or non-constitutive AhR agonists of Formula (I) and (II) for the inhibition of cancer cell growth and parameters that characterize tumor metastasis, such as tumor cell invasiveness.
1. A pharmaceutical composition comprising an aryl hydrocarbon receptor (AhR) modulator according to Formula (Ia) and a pharmaceutically acceptable excipient, carrier or stabilizer:
wherein:
X′ is H, unsubstituted alkyl, aminosulfonyl, acyl, aryl, or heteroaryl, where each of aminosulfonyl, acyl, aryl, or heteroaryl may be optionally substituted;
n is 0-6;
R 2 is H, alkyl, acyl, heteroaryl, arylalkyl, cycloalkyl, heteroarylalkyl, heterocyclyl, or haloalkyl, each of which may be optionally substituted;
R 3 , R 4 , R 5 and R 6 are independently H, alkyl, acyl, halo, aryl, or heteroaryl, each of which may be optionally substituted; or
a steroisomer or
pharmaceutically acceptable salt thereof; and
wherein the pharmaceutical composition is formulated as a capsule, pill, caplet or tablet.
2. A pharmaceutical composition comprising an aryl hydrocarbon receptor (AhR) modulator CB7993113 of the chemical structure
or a stereoisomer or pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable excipient, carrier or stabilizer,
wherein the pharmaceutical composition is formulated as a capsule, pill, caplet or tablet.
3. A pharmaceutical composition comprising an aryl hydrocarbon receptor (AhR) modulator according to Formula (Ia), which has the chemical structure
wherein:
X′ is optionally substituted amino,
n is 0-6,
R 2 is optionally substituted heteroaryl, and
R 3 , R 4 , R 5 and R 6 are independently H,
or a stereoisomer or pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable excipient, carrier or stabilizer,
wherein the pharmaceutical composition is formulated as a capsule, pill, caplet or tablet.
4. The pharmaceutical composition of claim 1 or claim 2 or claim 3 , wherein the pharmaceutical composition is free of lactose.