IP Library Granted Patent US 12,275,715
Granted Patent B2
US 12,275,715 · App. 18/506,060 · Granted Apr 15, 2025

Pyridin-2(1H)-one quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors

Inventors: Jian Lin (Acton, MA); Anna Ericsson (Shrewsbury, MA); Ann-Marie Campbell (Monroe, CT); Gary Gustafson (Ridgefield, CT); Zhongguo Wang (Lexington, MA); R. Bruce Diebold (Waltham, MA); Susan Ashwell (Carlisle, MA); David R. Lancia, Jr. (Boston, MA); Justin Andrew Caravella (Cambridge, MA); Wei Lu (Newton, MA)
Assignee: FORMA Therapeutics, Inc.
C07D401/12A61P35/00C07D401/14C07D471/04A61K31/47
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,275,715
App. No.
18/506,060
Granted
Apr 15, 2025
Kind
B2
Abstract

The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: where A, U, W 1 , W 2 , W 3 , R 1 -R 6 , and R 9 are described herein.

Claims (110)

1. A compound of Formula I:

or pharmaceutical salt thereof,

wherein:

each W 1 and W 2 is independently CH, CF or N;

W 3 is independently, CR 2 or N;

U is N or CR 6 ;

A is selected from the group consisting of H, D, halogen, CN, —CHO, —COOH, —COOR, —C(O)NH 2 , —C(O)NHR, R′S(O) 2 —, —O(CH 2 ) n C(O)R′, R′S(O)—, heteroaryl, —SOMe, —SO 2 Me,

wherein X and Y are independently in each occurrence C, N, NR′, S, and O, provided that the ring containing X and Y cannot have more than 4 N or NH atoms or more than one S or O atoms, and wherein the S and O are not contiguous;

R and R′ at each occurrence are independently selected from the group consisting of H, OH, CN, —CH 2 CN, halogen, —NR 7 R 8 , CHCF 2 , CF 3 , C 1 -C 6 alkyl, R 7 S(O) 2 —, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkylalkyl, 3- to 8-membered heterocyclyl, aryl, and heteroaryl, wherein each R and R′ are optionally substituted with one or more substituents selected from the group consisting of OH, halogen, C 1 -C 6 alkoxy, NH 2 , R 7 S(O) 2 —, CN, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, heteroaryl, and R 7 S(O)—;

R 1 is independently OH, CN, halogen, CHCF 2 , CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl, wherein each C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl is optionally substituted one or more times with substituents selected from the group consisting of halogen, OH, NH 2 , CN, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

each R 2 is independently H, OH, CN, halogen, CF 3 , CHF 2 , benzyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, NH 2 , —O(CH 2 ) n R′, —O(CH 2 ) n C(O)NHR′, —O(CH 2 ) n C(O)R′, NHR 7 , —N(R 7 )(R 8 ), NHC(O)R 7 , NHS(O)R 7 , NHS(O) 2 R 7 , NHC(O)OR 7 , NHC(O)NHR 7 , —S(O) 2 NHR 7 , NHC(O)N(R 8 )R 7 , OCH 2 R 7 , CHRR′ or OCHR′R 7 , wherein C 1 -C 6 alkyl, C 1 -C 6 alkoxy is optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl substituted with one or more halogen, 3- to 8-membered heterocyclyl, aryl, -heteroaryl-C(O)NH 2 , and heteroaryl;

or R 1 and R 2 can combine to form a C 4 -C 6 cycloalkyl or a 3- to 8-membered heterocyclyl containing at least one atom selected from the group consisting of N, O, and S;

R 3 is H, C 1 -C 6 alkyl, or —OH;

R 4 and R 5 are independently H, halogen, CH 2 OH, C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with halogen, or R 4 and R 5 when combined can form a C 3 -C 6 cycloalkyl or C 3 -C 6 heterocyclyl;

each R 6 is H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkoxy substituted with one or more halogen, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl, or C 1 -C 6 alkyl substituted with one or more of halogen, oxo, or C 1 -C 6 alkoxy;

R 7 and R 8 are independently H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, 3- to 8-membered heterocyclyl, aryl, and heteroaryl; or when combined R 7 and R 8 can form a 3- to 8-membered heterocyclyl or heteroaryl ring, wherein each of R 7 and R 8 are optionally substituted with halogen;

R 9 is independently H, D, CD3, CF 3 , C 1 -C 6 alkyl, C 2 -6 alkenyl, C 3 -6 alkynyl, C 3 -C 8 cycloalkyl, wherein the alkyl, alkenyl, alkynyl, and cycloalkyl is optionally substituted with amino, OH, halo, or alkoxy;

n is 0, 1, or 2; and

r is 0, 1, or 2;

with the proviso that when A is H, then R 1 is not C 1 -C 6 alkyl or C 1 -C 6 alkoxy and R 1 and R 2 cannot combine to form a 3- to 8-membered heterocyclyl.

2. A pharmaceutical composition comprising the compound according to claim 1 and pharmaceutically acceptable carrier.

3. A method of treating a disease or disorder associated with mutant isocitrate dehydrogenase, wherein the disease or disorder is glioma, glioblastoma multiforme (GBM), acute myeloid leukemia (AML), chondrosarcoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), or a solid tumor, comprising administering to a patient in need thereof a compound of claim 1 .

4. A method of treating glioma, glioblastoma multiforme (GBM), acute myeloid leukemia (AML), chondrosarcoma, intrahepatic cholangiocarcinoma (IHCC), myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), or a solid tumor, comprising administering to a patient in need thereof a compound of claim 1 .

5. The method of claim 4 , wherein the compound is of the Formula Ia:

6. The method of claim 4 , wherein the compound is of the Formula Ia-1:

7. The method of claim 4 , wherein the compound is of the Formula Ia-2:

8. The method of claim 4 , wherein the compound is of the Formula Ib:

9. The method of claim 4 , wherein the compound is of the Formula Ib-1:

10. A compound of claim 1 selected from:

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-6-oxo-1-(trifluoromethyl)-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[6-chloro-7-(2-hydroxypropan-2-yl)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-7-cyclopropyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-{6-chloro-7-[(2-hydroxy-2-methylpropyl)amino]-2-oxo-1,2-dihydroquinolin-3-yl}ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[7-(azetidin-1-yl)-6-chloro-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[7-(azetidin-1-yl)-6-chloro-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[6-chloro-7-(3,3-difluoroazetidin-1-yl)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

6-chloro-3-[(1S)-1-{[1-methyl-2-oxo-6-(1H-1,2,3,4-tetrazol-1-yl)-1,2-dihydropyridin-3-yl]amino}ethyl]-1,2-dihydroquinolin-2-one;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carboxamide;

5-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

6-chloro-3-{[(1-ethyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

5-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-6-oxo-1,6-dihydropyridine-2-carbonitrile;

6-chloro-3-{[(1-cyclopropyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(1,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

3-{[(6-bromo-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-6-chloro-1,2-dihydroquinolin-2-one;

6-chloro-3-({[2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl]amino}methyl)-1,2-dihydroquinolin-2-one;

6-chloro-3-({[1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl]amino}methyl)-1,2-dihydroquinolin-2-one;

methyl 5-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-6-oxo-1,6-dihydropyridine-3-carboxylate;

6-chloro-7-methoxy-3-{[(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1R)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyrazine-2-carbonitrile;

5-{[(1R)-1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[1-(6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1R)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1R)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-({1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl}amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-{6-chloro-2-oxo-7-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-dihydroquinolin-3-yl}ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[6-chloro-7-(cyclopropylmethoxy)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-[(1-{6-chloro-7-[(3,3-difluorocyclobutyl)methoxy]-2-oxo-1,2-dihydroquinolin-3-yl}ethyl)amino]-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[6-chloro-2-oxo-7-(propan-2-yloxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-8-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1R)-1-(7-chloro-3-oxo-3,4-dihydroquinoxalin-2-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile; or

5-{[(1S)-1-(7-chloro-3-oxo-3,4-dihydroquinoxalin-2-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile.

11. The compound of claim 10 selected from:

5-{[(1S)-1-[6-chloro-7-(3,3-difluoroazetidin-1-yl)-2-oxo-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-[(1-{6-chloro-7-[(3,3-difluorocyclobutyl)methoxy]-2-oxo-1,2-dihydroquinolin-3-yl}ethyl)amino]-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile; or

methyl 5-{[(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)methyl]amino}-6-oxo-1,6-dihydropyridine-3-carboxylate.

12. A pharmaceutical composition comprising the compound according to claim 10 and pharmaceutically acceptable carrier.

13. A method of treating a cell proliferative disease comprising administering to a patient in need thereof a compound of claim 10 , wherein the disease is acute myeloid leukemia (AML).

14. A method of treating a cancer comprising administering to a patient in need thereof a compound of claim 10 , wherein the cancer is acute myeloid leukemia (AML).

15. A method of inhibiting mutant isocitrate dehydrogenase comprising administering to a patient in need thereof a compound of claim 10 .

16. A method of reducing 2-hydroxyglutarate comprising administering to a patient in need thereof a compound of claim 10 .

17. A method of inhibiting mutant isocitrate dehydrogenase comprising administering to a patient in need thereof a compound of claim 1 , wherein the compound is selected from:

6-chloro-7-methoxy-3-{[(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1R)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyrazine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-{6-chloro-2-oxo-7-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-dihydroquinolin-3-yl}ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile; or

5-{[(1S)-1-(6-chloro-8-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile.

18. A method of reducing 2-hydroxyglutarate comprising administering to a patient in need thereof a compound of claim 10 , wherein the compound is selected from:

6-chloro-7-methoxy-3-{[(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-1,2-dihydroquinolin-2-one;

6-chloro-3-{[(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)amino]methyl}-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-2-one;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1R)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyrazine-2-carbonitrile;

5-{[(1S)-1-(6-chloro-7-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-[6-chloro-2-oxo-7-(pyridin-2-ylmethoxy)-1,2-dihydroquinolin-3-yl]ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile;

5-{[(1S)-1-{6-chloro-2-oxo-7-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-dihydroquinolin-3-yl}ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile; or

5-{[(1S)-1-(6-chloro-8-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile.

19. A method of treating chondrosarcoma comprising administering to a patient in need thereof a therapeutically effective amount of 5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile

or a pharmaceutically acceptable salt, an enantiomer, a hydrate, a solvate, a prodrug, an isomer, or a tautomer thereof.

20. The method of claim 19 , wherein the method comprises administering 5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile

or a pharmaceutically acceptable salt thereof.

21. The method of claim 19 , wherein the method comprises administering 5-{[(1S)-1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl]amino}-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile

22. The method of claim 19 , wherein the chondrosarcoma is characterized by the presence of an IDH1 mutation.

23. The method of claim 22 , wherein the IDH1 mutation is selected from R132H mutation, 132C mutation, R132G mutation, R132S mutation and R132L mutation.

Assignments (4)
SECURITY INTEREST Recorded May 8, 2026
From: RIGEL PHARMACEUTICALS, INC.
To: MIDCAP FUNDING IV TRUST
Reel/Frame 075576/0880 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 8, 2024
From: LIN, JIAN; ERICSSON, ANNA; CAMPBELL, ANN-MARIE; GUSTAFSON, GARY; WANG, ZHONGGUO; DIEBOLD, R. BRUCE; ASHWELL, SUSAN; LANCIA, DAVID R., JR.; CARAVELLA, JUSTIN ANDREW; LU, WEI
To: FORMA THERAPEUTICS, INC.
Reel/Frame 067353/0327 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 8, 2024
From: FORMA THERAPEUTICS, INC.
To: FORMA TM2, INC.
Reel/Frame 067353/0344 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 8, 2024
From: FORMA TM2, INC.
To: FORMA THERAPEUTICS, INC.
Reel/Frame 067353/0362 →
Continuity (11)
Continuation 17984069 · Nov 9, 2022
Continuation 17101018 · Nov 23, 2020
Continuation 16712951 · Dec 12, 2019
Continuation 16290240 · Mar 1, 2019
Continuation 15964844 · Apr 27, 2018
Continuation 15452256 · Mar 7, 2017
Continuation 14858167 · Sep 18, 2015
Provisional Application 62150812 · Apr 21, 2015
Provisional Application 62128089 · Mar 4, 2015
Provisional Application 62053006 · Sep 19, 2014
Related Publication 20240150319A1 · May 9, 2024
References Cited (177)
US 5262564A · Kun et al. · 1993 [cited by applicant]
US 9073941B2 · Wong et al. · 2015 [cited by applicant]
US 9624175B2 · Lin et al. · 2017 [cited by applicant]
US 9624216B2 · Lin et al. · 2017 [cited by applicant]
US 9771349B2 · Lin · 2017 [cited by examiner]
US 9815817B2 · Lin et al. · 2017 [cited by applicant]
US 9834539B2 · Lin · 2017 [cited by examiner]
US 10005734B2 · Lin et al. · 2018 [cited by applicant]
US 10253015B2 · Lin · 2019 [cited by examiner]
US 10266495B2 · Lin et al. · 2019 [cited by applicant]
US 10280150B2 · Lin et al. · 2019 [cited by applicant]
US 10294206B2 · Lin et al. · 2019 [cited by applicant]
US 10407419B2 · Lin et al. · 2019 [cited by applicant]
US 10414752B2 · Lin · 2019 [cited by examiner]
US 10550098B2 · Lin · 2020 [cited by examiner]
US 10550099B2 · Lin et al. · 2020 [cited by applicant]
US 10577329B2 · Lin et al. · 2020 [cited by applicant]
US 10807976B2 · Lin et al. · 2020 [cited by applicant]
US 10889567B2 · Lin · 2021 [cited by examiner]
US 11498913B2 · Lin · 2022 [cited by examiner]
US 20030105124A1 · Sobolov-Jaynes · 2003 [cited by applicant]
US 20040106645A1 · Blackburn et al. · 2004 [cited by applicant]
US 20120184548A1 · Dominique et al. · 2012 [cited by applicant]
US 20120184562A1 · Luk · 2012 [cited by applicant]
US 20140235620A1 · Caferro et al. · 2014 [cited by applicant]
US 20160083349A1 · Lin et al. · 2016 [cited by applicant]
US 20160083365A1 · Lin et al. · 2016 [cited by applicant]
US 20160083366A1 · Lin et al. · 2016 [cited by applicant]
US 20160083367A1 · Lin et al. · 2016 [cited by applicant]
US 20160311774A1 · Lin et al. · 2016 [cited by applicant]
US 20160311818A1 · Lin et al. · 2016 [cited by applicant]
US 20170174658A1 · Lin et al. · 2017 [cited by applicant]
US 20180086733A1 · Lin et al. · 2018 [cited by applicant]
US 20180118732A1 · Lin et al. · 2018 [cited by applicant]
US 20180134682A1 · Lin et al. · 2018 [cited by applicant]
US 20180141910A1 · Lin et al. · 2018 [cited by applicant]
US 20180312487A1 · Lin et al. · 2018 [cited by applicant]
US 20180327361A1 · Lin et al. · 2018 [cited by applicant]
US 20180327382A1 · Lin et al. · 2018 [cited by applicant]
US 20190135781A1 · Lin et al. · 2019 [cited by applicant]
US 20190202790A1 · Lin et al. · 2019 [cited by applicant]
US 20190210970A1 · Lin et al. · 2019 [cited by applicant]
US 20190210995A1 · Lin et al. · 2019 [cited by applicant]
US 20190263778A1 · Lin et al. · 2019 [cited by applicant]
US 20190263779A1 · Lin et al. · 2019 [cited by applicant]
US 20200010464A1 · Lin et al. · 2020 [cited by applicant]
US 20200115343A1 · Lin et al. · 2020 [cited by applicant]
US 20200223822A1 · Lin et al. · 2020 [cited by applicant]
CN 102558049A · 2012 [cited by applicant]
CN 103814020A · 2014 [cited by applicant]
EP 0481802A1 · 1992 [cited by applicant]
JP 2013513613A · 2013 [cited by applicant]
JP 2017528487A · 2017 [cited by applicant]
JP 2017528491A · 2017 [cited by applicant]
JP 2017528492A · 2017 [cited by applicant]
RU 2284325C2 · 2006 [cited by applicant]
WO WO2004043936A1 · 2004 [cited by applicant]
WO WO200595382A1 · 2005 [cited by applicant]
WO WO2006054912A1 · 2006 [cited by applicant]
WO WO2007117778A2 · 2007 [cited by applicant]
WO WO2008010964A1 · 2008 [cited by applicant]
WO WO2008069242A1 · 2008 [cited by applicant]
WO WO2008131547A1 · 2008 [cited by applicant]
WO WO2010144338A1 · 2010 [cited by applicant]
WO WO2011072174A1 · 2011 [cited by applicant]
WO WO2012079532A1 · 2012 [cited by applicant]
WO WO2012129562A2 · 2012 [cited by applicant]
WO WO2012171506A1 · 2012 [cited by applicant]
WO WO2013046136A1 · 2013 [cited by applicant]
WO WO2013096820A1 · 2013 [cited by applicant]
WO WO2013102431A1 · 2013 [cited by applicant]
WO WO2014141153A1 · 2014 [cited by applicant]
WO WO2015003146A1 · 2015 [cited by applicant]
WO WO2015121210A1 · 2015 [cited by applicant]
WO WO2016044781A1 · 2016 [cited by applicant]
WO WO2016044782A1 · 2016 [cited by applicant]
WO WO2016044787A1 · 2016 [cited by applicant]
WO WO2016044789A1 · 2016 [cited by applicant]
WO WO2016106331A1 · 2016 [cited by applicant]
WO WO2016108045A2 · 2016 [cited by applicant]
WO WO2016171755A1 · 2016 [cited by applicant]
WO WO2016171756A1 · 2016 [cited by applicant]
WO WO2017019429A1 · 2017 [cited by applicant]
WO WO2017146795A1 · 2017 [cited by applicant]
WO WO2017213910A1 · 2017 [cited by applicant]
WO WO2017223202A1 · 2017 [cited by applicant]
WO WO2018111707A1 · 2018 [cited by applicant]
Abbas, S. et al., Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value, Blood, 116(12): 2122-2126 (2010). [cited by applicant]
Amary, M.F. et al., IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours, J Pathol, 224: 334-343 (2011). [cited by applicant]
Asteian, A. et al., Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPAR? Antagonists, ACS Med. Chem. Lett., 6: 998-1003 (2015). [cited by applicant]
Badr, M.Z.A. et al., Reaction of Quinoxaline Derivatives with Nucleophilic Reagents, , Bull Chem Soc Jpn, 56(1): 326-330 (1983). [cited by applicant]
Balss, J. et al., Analysis of the [cited by applicant]
Bertus, P. and Szymoniak, J., A direct synthesis of 1-aryl- and 1-alkenylcyclopropylamines from aryl and alkenyl Nitriles Journal of Organic Chemistry, 68(18): 7133-7136 (2003). [cited by applicant]
Blackburn, C. et al., Identification and characterization of amino-piperidinequinolones and quinazolinones as MCHr1 antagonists, Bio. and Med. Chem. Letters, 16(10):2621-2627 (2006). [cited by applicant]
Boddu, P. and Borthakur, G., Therapeutic targeting of isocitrate dehydrogenase mutant AML, Expert Opinion on Investigational Drugs, 26(5): 525-529 (2017). [cited by applicant]
Borg, G. et al., One-pot asymmetric synthesis of tert-butanesulfinyl-protected amines from ketones by the in situ reduction of tert-butanesulfinyl ketimines, Tetrahedron Letters, 40: 6709-6712 (1999). [cited by applicant]
Borger, D.R., et al., Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping, The Oncologist 17, 72-79 (2012). [cited by applicant]
Cairns, R.A. and Mak, T.W., Oncogenic Isocitrate Dehydrogenase Mutations: Mechanisms, Models, and Clinical Opportunities, Cancer Discovery, 730-741 (2013). [cited by applicant]
Caravella, J. A. et al., Structure-based design and identification of FT-2102 (olutasidenib), a potent mutant-selective IDH1 inhibitor, J Med Chem, doi: 10.1021/acs.jmedchem.9b01423, Epub ahead of print (2020). [cited by applicant]
Chaturvedi, A. et al., Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo, Leukemia, 31: 2020-2028 (2017). [cited by applicant]
Cho, Y.S. et al., Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor, ACS Med Chem Lett., 8(10): 1116-1121 (2017). Supporting Information, 31 pages. [cited by applicant]
Chowdhury, R. et al., The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases, EMBO Rep., 12: 463-469 (2011). [cited by applicant]
Cui, Z. et al., Structure and properties of N-heterocycle-containing benzotriazoles as UV absorbers, Journal of Molecular Structure, 1054: 94-99 (2013). [cited by applicant]
Damato, S. et al., IDH1 mutations are not found in cartilaginous tumours other than central and perlosteal chondrosarcomas and enchondromas, Histopathology, 60: 357-376 (2011). [cited by applicant]
Dang, L. et al., Cancer-associated IDH1 mutations produce 2-hydroxyglutarate, Nature, 462: 739-744 (2009). [cited by applicant]
Dang, L. et al., IDH mutations in glioma and acute myeloid leukemia, Trends Mol. Med., 16(9): 387-397 (2010). [cited by applicant]
Database Caplus (Online) Chemical Abstracts Service, Columbus, Ohio, US; retrieved from STN Database accession No. 1987: 407040 abstract, Prostakov, N.S. et al., Synthesis of substituted 2-pyridones and 4-aza-3-fluoreno… [cited by applicant]
Database Registry (Online) Chemical Abstracts Service, Columbus, Ohio, US; Database accession No. 1434379-53-9 (Jun. 5, 2013). [cited by applicant]
Database Registry (Online) Chemical Abstracts Service, Columbus, Ohio, US; Database accession No. 1497653-96-9 (Dec. 18, 2013). [cited by applicant]
Database Registry (Online) Chemical Abstracts Service, Columbus, Ohio, US; Database accession No. 1567357-55-4 (Mar. 12, 2014). [cited by applicant]
Database Registry (Online) Chemical Abstracts Service, Columbus, Ohio, US; Database accession No. 1567456-94-3 (Mar. 12, 2014). [cited by applicant]
De Botton, S. et al., Clinical Safety and Activity of AG-120, a First-in-Class, Potent Inhibitor of the IDH1-Mutant Protein, in a Phase 1 Study of Patients with Advanced IDH-Mutant Hematologic Malignancies. European Hem… [cited by applicant]
Deng, G. et al., Selective Inhibition of Mutant Isocitrate Dehydrogenase 1 (IDH1) via Disruption of a Metal Binding Network by an Allosteric Small Molecule, The Journal of Biological Chemistry, 290: 762-774 (2014). [cited by applicant]
Dinardo, C.D. et al., Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia, Blood, 121(24): 4917-1924 (2013). [cited by applicant]
Fatima, S., Molecular docking and 3D-QSAR studies on inhibitors of DNA damage signaling enzyme human PARP-1, J Receptors and Signal Transduction, 32(4) 214-224 (2012). [cited by applicant]
Figueroa, M.E et al., Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation, Cancer Cell, 18:553-567 (2010). [cited by applicant]
Flavahan, W.A. et al., Insulator dysfunction and oncogene activation in IDH mutant gliomas, Nature, 1-16 (2015). [cited by applicant]
FORMA Therapeutics, Discovery and Optimization of a Novel Series of Inhibitors of mt-IDH1, 7th Annual Advances in Chemical Sciences Symposium, Presentation, 21 slides (May 4, 2018). [cited by applicant]
Gaal, J. et al., Isocitrate Dehydrogenase Mutations are Rare in Pheochromocytomas and Paragangliomas, J. Clin. Endocrinol. Metab., 95(3): 1274-1278 (2010). [cited by applicant]
Gross, S. et al., Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations, J. Exp. Med., 207(2): 339-344 (2010). [cited by applicant]
Hayden, J.T. et al., Frequent IDH1 mutations in supratentorial primitive neuroectodermal tumors (sPNET) of adults but not children, Cell Cycle, 8(11): 1806-1807 (2009). [cited by applicant]
He, Y. et al., Asperspiropene A, a novel fungal metabolite as an inhibitor of cancer-associated mutant isocitrate dehydrogenase 1, Org. Chem. Front., 1-8 (2017). [cited by applicant]
International Search Report for PCT/US2015/051044, 4 pages (mailed Nov. 23, 2015). [cited by applicant]
International Search Report for PCT/US2015/051046, 3 pages (mailed Oct. 30, 2015). [cited by applicant]
International Search Report for PCT/US2015/051053, 4 pages (mailed Oct. 28, 2015). [cited by applicant]
International Search Report for PCT/US2015/051055, 3 pages (mailed Nov. 13, 2015). [cited by applicant]
International Search Report for PCT/US2015/051056, 4 pages (mailed Nov. 20, 2015). [cited by applicant]
International Search Report for PCT/US2015/051059, 3 pages (mailed Oct. 30, 2015). [cited by applicant]
Jones, S.; et al., Discovery and Optimization of Allosteric Inhibitors of Mutant Isocitrate Dehydrogenase 1 (R132H IDH1) Displaying Activity in Human Acute Myeloid Leukemia Cells, J. Med. Chem., 59(24): 11120-11137 (201… [cited by applicant]
Kombarov, R.V. et al., CA Accession No. 138:368869, abstract only of Chem of Het Compounds, 38(9): 1154-1155 (2002). [cited by applicant]
Law, J. M.; et al., Discovery of 8-Membered Ring Sulfonamides as Inhibitors of Oncogenic Mutant Isocitrate Dehydrogenase 1. ACS Medicinal Chemistry Letters, 7(10): 944-949 (2016). [cited by applicant]
Leese, C. L. and Rydon, H.N., Polyazanaphthalenes. Part I. Some derivatives of 1:4:5-triazanaphthalene and quinoxaline, PolyJournal of the Chemical Society, 303-309 (1995). [cited by applicant]
Levell, J. R. et al., Optimization of 3-pyrimidin-4-yl-oxazolidin-2-ones as allosteric and mutant specific inhibitors of IDH1, ACS Med. Chem. Lett., 8: 151-156 (2017). [cited by applicant]
Liu, G. et al., Synthesis of enantiomerically pure N-tert-butanesulfinyl imines (tertbutanesulfinimines) by the direct condensation of tert-butanesulfinamide with aldehydes and ketones. J. Org. Chem., 64(6): 1278-1284 (… [cited by applicant]
Liu, G.; et al., Catalytic asymmetric synthesis of tert-butane sulfinamide. Application to the asymmetric synthesis of amines. J. Am. Chem. Soc., 119(41): 9913-9914 (1997). [cited by applicant]
Liu, Z. et al., Inhibition of cancerassociated mutant isocitrate dehydrogenases: synthesis, structureactivity relationship, and selective antitumor activity. J. Med. Chem., 57: 8307-8318 (2014). [cited by applicant]
Losman, J-A. et al., (R)-2-Hydroxyglutarate is Sufficient to Promote Leukemogenesis and its Effects are Reversible, Science, 339 (6127): 1-9 (2013). [cited by applicant]
Lu, C., et al., IDH mutation impairs histone demethylation and results in a block to cell differentiation, Nature, 483:474-478 (2012). [cited by applicant]
Ma, R. and Yun, C. H., Crystal structures of pan-IDH inhibitor AG-881 in complex with mutant human IDH1 and IDH2, Biochem Biophys Res Commun, 503(4): 2912-2917 (2018). [cited by applicant]
Mamedov, V. A. et al., Synthesis and Functionalization of 3-Ethylquinoxalin-2(1H)-one, Russian Journal of Organic Chemistry, 41(4): 599-606 (2005). [cited by applicant]
Meth-Cohn, O. and Stanforth, S. P. The Vilsmeier-Haack reaction (Review), Compr. Org. Synth., 2: 777-779 (1991). [cited by applicant]
Mohamed, E.A. et al., CA Accession No. 122:160601, abstract only of Indian J Chem, Sect B: Org Chem Inc Med Chem, 34B(1): 21-26 (1995). [cited by applicant]
Morshed, M.N et al., Computational approach to the identification of novel Aurora-A inhibitors, Bloorg & Med Chem, 19: 907-916 (2011). [cited by applicant]
Okoye-Okafor , U.C et al., New IDH1 mutant inhibitors for treatment of acute myeloid leukemia, Nat. Chem. Biol., 11: 878-886 (2015). [cited by applicant]
Parsons, D. W.; et al., An integrated genomic analysis of human glioblastoma multiforme, Science, 321: 1807-1812 (2000). [cited by applicant]
Pelosi, E. et al., Isocitrate dehydrogenase mutations in human cancers: physiopathologie mechanisms and therapeutic Targeting. Journal of Exploratory Research in Pharmacology, 1: 20-34 (2016). [cited by applicant]
Penard-Lacronique, V. and, Bernard, O.A., IDH1, Histone Methylation, and So Forth, Cancer Cell, 30: 192-194 (2016). [cited by applicant]
Popovici-Muller, J. et al., Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancer, ACS Med. Chem. Lett., 9(4): 300-305 (2018). [cited by applicant]
Popovici-Muller, J. et al., Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo, ACS Med. Chem. Lett., 3(10): 850-855 (2012). [cited by applicant]
Prostakov, N.S. et al., Chemistry of Heterocyclic Compounds, Chocal, 22(7): 685-810 (1986). [cited by applicant]
Pusch, S. et al., Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 Mutant astrocytoma in vivo. Acta Neuropathologica, 133(4): 629-644 (2017). [cited by applicant]
Rohle, D., et al., An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells, Science, 340:626-630 (2013). [cited by applicant]
Schrader, F.C. et al., Novel Type II Fatty Acid Biosynthesis (Fas II) Inhibitors as Multistage Antimalarial Agents, Chem Med Chem, 8: 442-461 (2013). [cited by applicant]
Segall, M., Multi-parameter Optimisation in Drug Discovery: Quickly targeting compounds with a good balance of properties, Optibrium Ltd, ELRIG Drug Discovery 2011, 32 pages (Sep. 7, 2011). [cited by applicant]
Sellner, L. et al. Increased levels of 2-hydroxyglutarate in AML patients with IDH1-R132H and IDH2-R140Q mutations, Eur. J. Haematol., 85: 457-459 (2010). [cited by applicant]
Seltzer, M.J. et al., Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1, Cancer Research, 70(22): 8981-8987 (2010). [cited by applicant]
Shibata, T. et al., Mutant IDH1 Confers an in Vivo Growth in a Melanoma Cell Line with BRAF Mutation, Am. J. Pathol., 178(3): 1395-1402 (2011). [cited by applicant]
SRI Ramya, P.V et al., Curcumin inspired 2-chloro/phenoxy quinoline analogues: Synthesis and biological evaluation as potential anticancer agents, Bioorganic & Medicinal Chemistry Letters 28: 892-898 (2018). [cited by applicant]
Suman, P. et al., Synthesis and evaluation of functionalized aminobenzoboroxoles as potential anti-cancer agents, Journal of Organometallic Chemistry, 798(1): 125-131 (2015). [cited by applicant]
Tintori, C. et al., Identification of Hck Inhibitors as Hits for the Development of Antileukemia and Anti-HIV Agents, Chem Med Chem, 8: 1353-1360 (2013). [cited by applicant]
Turcan, S. et al., Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT Inhibitor Decitabine, Oncotarget, 4(10): 1729-1736 (2013). [cited by applicant]
Urban, D. J. et al., Assessing inhibitors of mutant isocitrate dehydrogenase using a suite of pre-clinical discovery assays, Scientific Reports 7(1): 12758 (2017). [cited by applicant]
Venkanna, P. et al., 2,4,6-Trichloro-1,3,5-triazine and N,N′-dimethylformamide as an effective Vilsmeier-Haack reagent for the synthesis of 2-chloro-3-formyl quinolines from acetanilides, Tetrahedron Letters, 56(37): 51… [cited by applicant]
Wager, T.T. et al., Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach to Enable Alignment of Druglike Properties. ACS Chem. Neurosci., 1(6): 435-449 (2010). [cited by applicant]
Wahl, D.R. et al., Glioblastoma Therapy Can be Augmented by Targeting IDH1-mediated NADPH Biosynthesis, Cancer Res, 77(4): 960-970 (2017). [cited by applicant]
Wai, J. et al., Synthesis and evaluation of 2-pyridinone derivatives as specific HIV-1 reverse transcriptase inhibitors. 3. Pyridyl and phenyl analogs of 3-aminopyridin-2(1 H)-one, J. Med. Chem., 36(2):249-255 (1993). [cited by applicant]
Wakayama, M. and Ellman, J.A., Recycling the tert-Butanesulfinyl Group in the Synthesis of Amines Using tert-Butanesulfinamide, J. Org. Chem., 74: 2646-2650 (2009). [cited by applicant]
Wang, F. et al., Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation, Science, 340: 622-626 (2013). [cited by applicant]
Wang, P. et al., Mutations in Isocitrate Dehydrogenase 1 and 2 Occur Frequently in Intrahepatic Cholangiocarcinomas and Share Hypermetylation Targets with Glioblastomas, Oncogene, 32(25): 3091-3100 (2013). [cited by applicant]
Wang, R. et al., Rapid Ti(OiPr)4 facilitated synthesis of a,a, a-trisubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions. Tetrahedron Letters, 50(50): 7070-7073 … [cited by applicant]
Ward, P.S. et al., The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzymatic activity that converts α-ketoglutarate to 2-hydroxyglutarate, Cancer Cell, 17(3): 225-234 (2010). [cited by applicant]
Wu, F. et al., Inhibition of cancer-associated mutant isocitrate dehydrogenases by 2-thiohydantoin compounds, J. Med. Chem., 58: 6899-6908 (2015). [cited by applicant]
Xu, X. et al., Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity, J Biol Chem., 279(32): 33946-33957 (2004). [cited by applicant]
Yan, H. et al., IDH1 and IDH2 mutations in gliomas, N. Engl. J. Med., 360: 765-773 (2009). [cited by applicant]
Yang, H. et al., and Clinical Perspectives IDH1 and IDH2 Mutations in Tumorigenesis: Mechanistic Insights, Clin Cancer Res, 18: 5562-5571 (2012). [cited by applicant]
Zhao, S. et al., Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1α, Science, 324(5924): 261-265 (2009). [cited by applicant]
Zheng, B. et al., Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase, ACS Medicinal Chemistry Letters, 4(6): 542-546 (2013). [cited by applicant]