MEK INHIBITORS AND USES THEREOF

1 .- 22 . (canceled)

23 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

each is independently a single or double bond;

each A is independently

 or optionally substituted 5-6 membered heteroaryl;

X 1 , X 2 , X 3 , and X 5 are independently CR 1 or N;

X 6 is C(O), O or NH;

X 7 is CH or N;

X 8 is N or O; or when X 8 is N, R 3 and R 8 , taken together with the N atom to which they attach form an optionally substituted 3-7 membered hetercycloalkyl ring;

each R 1 is independently hydrogen, deuterium, halo, —CN, optionally substituted C 1 -C 6 aliphatic, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 6 -C 10 heterocycloalkyl, or optionally substituted C 6 -C 10 aryl;

R 2 , R 3 , R 4 , and R 5 are independently hydrogen, C( 2 D) 3 , OC( 2 D) 3 , optionally substituted C 1 -C 6 aliphatic, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 6 -C 10 heterocycloalkyl, or optionally substituted C 6 -C 10 aryl; or R 5 is absent when X 7 is N forming a double bond with the sulfur atom;

each R 6 is independently hydrogen, deuterium, C( 2 D) 3 , optionally substituted C 1 -C 6 aliphatic, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 6 -C 10 heterocycloalkyl, optionally substituted C 6 -C 10 aryl, or both R 6 taken together with the atom to which they attach form an optionally substituted 3-7 membered hetercycloalkyl ring, or

R 5 and R 6 taken together with the atoms to which they attach form a 5-6 membered heterocycloalkyl ring; or

R 5 and X 5 or X 3 taken together with the atoms to which they attach form a 5-6 membered fused heterocycloalkyl or heteroaromatic ring; or

R 6 and X 5 or X 3 taken together with the atoms to which they attach form a 5-6 membered fused heterocycloalkyl ring;

R 7 is O or optionally substituted C 1 -C 6 aliphatic; and

R 8 is absent, hydrogen, deuterium, or optionally substituted C 1 -C 6 aliphatic.

24 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein X 1 , X 2 , X 3 , and X 5 are independently CR 1 .

25 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein X 6 is O.

26 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein X 7 is N.

27 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein A is

28 . The compound of claim 27 , or a pharmaceutically acceptable salt thereof, wherein X 8 is N.

29 . The compound of claim 27 , or a pharmaceutically acceptable salt thereof, wherein R 3 is optionally substituted C 3 -C 10 cycloalkyl.

30 . The compound of claim 27 , or a pharmaceutically acceptable salt thereof, wherein R 8 is hydrogen or optionally substituted C 1 -C 6 aliphatic.

31 . The compound of claim 24 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently hydrogen, halo, —CN, optionally substituted C 1 -C 6 aliphatic, optionally substituted C 1 -C 6 alkoxy, or optionally substituted C 3 -C 10 cycloalkyl.

32 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently hydrogen, halo, or optionally substituted C 1 -C 6 alkoxy.

33 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein R 2 is optionally substituted C 1 -C 6 aliphatic.

34 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein R 7 is O.

35 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein R 4 is optionally substituted C 1 -C 6 aliphatic.

36 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein R 5 is hydrogen.

37 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein each R 6 is independently hydrogen or optionally substituted C 1 -C 6 aliphatic.

38 . The compound of claim 23 , wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

39 . A pharmaceutical composition comprising the compound of claim 23 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

40 . A method of treating a disorder mediated by MEK, comprising administering a therapeutically effective amount of the compound of claim 23 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, to a subject in need thereof.

41 . A method for treating a cancer in a patient, comprising administering the compound of claim 23 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, to the patient.

42 . A method of inhibiting MEK activity, comprising contacting MEK or a KSR-MEK complex or a RAF-MEK complex with an effective amount of the compound of claim 23 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, to inhibit MEK activity.