IP Library Granted Patent US 12,662,488
Granted Patent B2
US 12,662,488 · App. 18/117,978 · Granted Jun 23, 2026

Spirocyclic compounds

Inventors: Christopher G. Nasveschuk (Stoneham, MA); Fabian Dey (Basel, CH); Annick Goergler (Colmar, FR); Roger Norcross (Basel, CH); Philipp Schmid (Basel, CH)
Assignee: C4 Therapeutics, Inc.
C07D487/10A61P35/00C07D519/00
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Quick Facts
Patent No.
US 12,662,488
App. No.
18/117,978
Filed
Mar 6, 2023
Granted
Jun 23, 2026
Kind
B2
Art Unit
1629
USPC
514/300
Abstract

The present invention provides compounds and intermediates. The present invention also provides compounds which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and their use for the treatment of abnormal cellular proliferation. The present invention also provides compounds that may be used as synthetic intermediates in the synthesis of bifunctional compounds used for targeted protein degradation.

Claims (32)

1 . A method of treating cancer in a subject in need thereof comprising administering an effective amount of a compound of formula:

or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutical composition,

wherein:

Y is NH or CH 2 ;

n is 0 or 1;

A is selected from the group consisting of

i.) aryl;

ii.) aryl substituted by R 1 ;

iii.) heteroaryl; and

iv.) heteroaryl substituted by R 2 ;

R 1 is selected from the group consisting of

i.) —C(═O)—O—C 1-6 -alkyl;

ii.) —COOH;

iii.) —NH—C(═O)—C 1-6 -alkyl;

iv.) —NH 2 ; and

v.) —NO 2 ;

R 2 is selected from the group consisting of

i.) —COOH;

ii.) —C(═O)—O—C 1-6 -alkyl;

iii.) —NH 2 ; and

iv.) —NO 2 .

2 . The method of claim 1 , wherein the subject is a human.

3 . The method of claim 2 , wherein A is aryl.

4 . The method of claim 2 , wherein A is heteroaryl.

5 . The method of claim 3 , wherein Y is NH and n is 0.

6 . The method of claim 3 , wherein Y is NH and n is 1.

7 . The method of claim 3 , wherein Y is CH 2 and n is 0.

8 . The method of claim 3 , wherein Y is CH 2 and n is 1.

9 . The method of claim 4 , wherein Y is NH and n is 0.

10 . The method of claim 4 , wherein Y is NH and n is 1.

11 . The method of claim 4 , wherein Y is CH 2 and n is 0.

12 . The method of claim 4 , wherein Y is CH 2 and n is 1.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 1, 2026
From: NORCROSS, ROGER; GOERGLER, ANNICK; SCHMID, PHILIPP; DEY, FABIAN
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 074545/0321 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 1, 2026
From: NASVESCHUK, CHRISTOPHER G.
To: C4 THERAPEUTICS, INC.
Reel/Frame 074545/0338 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 1, 2026
From: F. HOFFMANN-LA ROCHE AG
To: HOFFMANN-LA ROCHE INC.
Reel/Frame 074545/0372 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 1, 2026
From: HOFFMANN-LA ROCHE INC.
To: C4 THERAPEUTICS, INC.
Reel/Frame 074545/0404 →
Priority Claims (1)
EP 18175701 · Jun 4, 2018 · regional
Continuity (3)
Continuation 17103621 · Nov 24, 2020
Continuation PCTUS2019035223 · Jun 3, 2019
Related Publication 20240018156A1 · Jan 18, 2024
References Cited (185)
US 5635517A · Muller et al. · 1997 [cited by applicant]
US 6306663B1 · Kenten et al. · 2001 [cited by applicant]
US 7041298B2 · Deshaies et al. · 2006 [cited by applicant]
US 7208157B2 · Deshaies et al. · 2007 [cited by applicant]
US 20140302523A1 · Crews et al. · 2014 [cited by applicant]
US 20140356322A1 · Crews et al. · 2014 [cited by applicant]
US 20150025058A1 · Deutsch et al. · 2015 [cited by applicant]
US 20150119435A1 · Crews et al. · 2015 [cited by applicant]
US 20150274738A1 · Gray et al. · 2015 [cited by applicant]
US 20150291562A1 · Crew et al. · 2015 [cited by applicant]
US 20160022642A1 · Crews et al. · 2016 [cited by applicant]
US 20160045607A1 · Crew et al. · 2016 [cited by applicant]
US 20160046661A1 · Gray et al. · 2016 [cited by applicant]
US 20160058872A1 · Crew et al. · 2016 [cited by applicant]
US 20160176916A1 · Bradner et al. · 2016 [cited by applicant]
US 20160214972A1 · Jin et al. · 2016 [cited by applicant]
US 20160272639A1 · Crew et al. · 2016 [cited by applicant]
US 20170008904A1 · Crew et al. · 2017 [cited by applicant]
US 20170037004A1 · Crew et al. · 2017 [cited by applicant]
US 20180085465A1 · Bradner et al. · 2018 [cited by applicant]
US 20180134684A1 · Bradner et al. · 2018 [cited by applicant]
WO WO2002059106A1 · 2002 [cited by applicant]
WO WO2008027542A2 · 2008 [cited by applicant]
WO WO2008033567A1 · 2008 [cited by applicant]
WO WO2008039489A2 · 2008 [cited by applicant]
WO WO2008115516A2 · 2008 [cited by applicant]
WO WO2009042177A1 · 2009 [cited by applicant]
WO WO2009139880A1 · 2009 [cited by applicant]
WO WO2009145899A1 · 2009 [cited by applicant]
WO WO2010053732A1 · 2010 [cited by applicant]
WO WO2010107485A1 · 2010 [cited by applicant]
WO WO2013106646A2 · 2013 [cited by applicant]
WO WO2013124026A1 · 2013 [cited by applicant]
WO WO2013170147A1 · 2013 [cited by applicant]
WO WO2016065139A1 · 2016 [cited by applicant]
WO WO2016105518A1 · 2016 [cited by applicant]
WO WO2016146985A1 · 2016 [cited by applicant]
WO WO2016169989A1 · 2016 [cited by applicant]
WO WO2016191178A1 · 2016 [cited by applicant]
WO WO2016197032A1 · 2016 [cited by applicant]
WO WO2016197114A1 · 2016 [cited by applicant]
WO WO2017007612A1 · 2017 [cited by applicant]
WO WO2017024317A2 · 2017 [cited by applicant]
WO WO2017024318A1 · 2017 [cited by applicant]
WO WO2017024319A1 · 2017 [cited by applicant]
WO WO2017079267A1 · 2017 [cited by applicant]
WO WO2017161119A1 · 2017 [cited by applicant]
WO WO2017176708A1 · 2017 [cited by applicant]
WO WO2017176957A1 · 2017 [cited by applicant]
WO WO2017176958A1 · 2017 [cited by applicant]
WO WO2017180417A1 · 2017 [cited by applicant]
WO WO2017201069A1 · 2017 [cited by applicant]
WO WO2017201449A1 · 2017 [cited by applicant]
WO WO2018051107A1 · 2018 [cited by applicant]
WO WO2018052945A1 · 2018 [cited by applicant]
WO WO2018052949A1 · 2018 [cited by applicant]
WO WO2018053354A1 · 2018 [cited by applicant]
WO WO2018071606A1 · 2018 [cited by applicant]
WO WO2018085247A1 · 2018 [cited by applicant]
WO WO2018102067A2 · 2018 [cited by applicant]
WO WO2018102725A1 · 2018 [cited by applicant]
WO WO2018118598A1 · 2018 [cited by applicant]
WO WO2018118947A1 · 2018 [cited by applicant]
WO WO2018119357A1 · 2018 [cited by applicant]
WO WO2018119441A1 · 2018 [cited by applicant]
WO WO2018119448A1 · 2018 [cited by applicant]
WO WO2018140809A1 · 2018 [cited by applicant]
WO WO2018144649A1 · 2018 [cited by applicant]
WO WO2018169777A1 · 2018 [cited by applicant]
WO WO2018189554A1 · 2018 [cited by applicant]
WO WO2019032632A1 · 2019 [cited by applicant]
Registry Entry for 908105-74-8 published Sep. 21, 2016. (Year: 2016). [cited by examiner]
Registry Entry for 1394538-03-4 published Jan. 6, 2014 (Year: 2014). [cited by examiner]
Registry Entry for 1413479-09-0 published Dec. 11, 2012. (Year: 2012). [cited by examiner]
U.S. Pat. No. 10,646,575 B2, U.S. Appl. No. 16/186,339, Philips et al., May 12, 2020. [cited by applicant]
U.S. Pat. No. 10,660,968 B2, U.S. Appl. No. 16/186,334, Philips et al., May 26, 2020. [cited by applicant]
U.S. Pat. No. 10,849,982 B2, U.S. Appl. No. 16/186,341, Phillips et al., Dec. 1, 2020. [cited by applicant]
U.S. Pat. No. 10,905,768 B2, U.S. Appl. No. 16/872,225, Phillips et al., Feb. 2, 2021. [cited by applicant]
U.S. Pat. No. 11,185,592 B2, U.S. Appl. No. 16/882,236, Phillips et al., Nov. 30, 2021. [cited by applicant]
U.S. Pat. No. 11,254,672 B2, U.S. Appl. No. 16/809,325, Norcross et al., Feb. 22, 2022. [cited by applicant]
U.S. Pat. No. 11,401,256 B2, U.S. Appl. No. 16/809,345, Norcross et al., Aug. 2, 2022. [cited by applicant]
U.S. Pat. No. 11,407,732 B2, U.S. Appl. No. 17/498,617, Henderson et al., Aug. 9, 2022. [cited by applicant]
U.S. Pat. No. 11,459,335 A1, U.S. Appl. No. 16/721,650, Phillips et al., Oct. 4, 2022. [cited by applicant]
U.S. Pat. No. 11,524,949 A1, U.S. Appl. No. 16/874,475, Phillips et al., Dec. 13, 2022. [cited by applicant]
U.S. Pat. No. 11,584,748 A1, U.S. Appl. No. 17/072,896, Nasveschuk et al., Feb. 21, 2023. [cited by applicant]
U.S. Pat. No. 11,623,929 A1, U.S. Appl. No. 17/103,621, Nasveschuk et al., Apr. 11, 2023. [cited by applicant]
U.S. Pat. No. 11,673,902 B2, U.S. Appl. No. 17/843,769, Nasveschuk et al., Jun. 13, 2023. [cited by applicant]
U.S. Pat. No. 11,691,972 A1, U.S. Appl. No. 17/541,035, Nasveschuk et al., Jul. 4, 2023. [cited by applicant]
U.S. Pat. No. 11,753,397 A1, U.S. Appl. No. 17/031,550, Henderson et al., Sep. 12, 2023. [cited by applicant]
U.S. Pat. No. 11,787,802 A1, U.S. Appl. No. 17/576,582, Norcross et al., Oct. 17, 2023. [cited by applicant]
U.S. Pat. No. 11,802,131 A1, U.S. Appl. No. 16/809,336, Norcross et al., Oct. 31, 2023. [cited by applicant]
US 2020/0308171 A1, U.S. Appl. No. 16/903,237, Jaeschke et al., Oct. 1, 2020. [cited by applicant]
US 2021/0198256 A1, U.S. Appl. No. 17/192,634, Nasveschuk et al., Jul. 1, 2021. [cited by applicant]
US 2022/0313826 A1, U.S. Appl. No. 17/107,781, Phillips et al., Oct. 6, 2022. [cited by applicant]
US 2022/0313827 A1, U.S. Appl. No. 17/121,389, Phillips et al., Oct. 6, 2022. [cited by applicant]
US 2022/0372016 A1, U.S. Appl. No. 17/351,935, Phillips et al., Nov. 24, 2022. [cited by applicant]
US 2023/0014124 A1, U.S. Appl. No. 17/164,446, Phillips et al., Jan. 19, 2023. [cited by applicant]
US 2023/0019060 A1, U.S. Appl. No. 17/465,583, Nasveschuk et al., Jan. 19, 2023. [cited by applicant]
US 2023/0060334 A1, U.S. Appl. No. 17/901,775, Nasveschuk et al., Mar. 2, 2023. [cited by applicant]
US 2023/0082430 A1, U.S. Appl. No. 17/723,199, Henderson et al., Mar. 16, 2023. [cited by applicant]
US 2023/0095223 A1, U.S. Appl. No. 17/524,558, Phillips et al., Mar. 30, 2023. [cited by applicant]
US 2023/0145336 A1, U.S. Appl. No. 18/084,380, Nasveschuk et al., May 11, 2023. [cited by applicant]
US 2023/0190760 A1, U.S. Appl. No. 18/106,893, Proia et al., Jun. 22, 2023. [cited by applicant]
US 2023/0192643 A1, U.S. Appl. No. 17/878,753, Norcross et al., Jun. 22, 2023. [cited by applicant]
UA 2023/0233692 A1, U.S. Appl. No. 18/105,735, Henderson et al., Jul. 27, 2023. [cited by applicant]
US 2023/0279023 A1, U.S. Appl. No. 17/959,144, Phillips et al., Sep. 7, 2023. [cited by applicant]
US 2023/0339902 A1, U.S. Appl. No. 18/134,985, Nasveschuk et al., Oct. 26, 2023. [cited by applicant]
US 2023/0357180 A1, U.S. Appl. No. 18/079,815, Phillips et al., Nov. 9, 2023. [cited by applicant]
U.S. Appl. No. 18/240,231, Henderson et al., filed Aug. 30, 2023. [cited by applicant]
U.S. Appl. No. 18/100,992, Nasveschuk et al., filed Jan. 24, 2023. [cited by applicant]
U.S. Appl. No. 18/144,800, Nasveschuk et al., filed May 8, 2023. [cited by applicant]
U.S. Appl. No. 18/134,971, Nasveschuk et al., filed Apr. 14, 2023. [cited by applicant]
U.S. Appl. No. 18/134,990, Nasveschuk et al., filed Apr. 14, 2023. [cited by applicant]
U.S. Appl. No. 17/965,199, Nasveschuk et al., filed Oct. 13, 2022. [cited by applicant]
U.S. Appl. No. 18/370,186, Norcross et al., filed Sep. 19, 2023. [cited by applicant]
U.S. Appl. No. 18/385,277, Norcross et al., filed Oct. 30, 2023. [cited by applicant]
Bartlett, et al. “The evolution of thalidomide and its IMiD derivatives as anticancer agents.” Nat Rev Cancer 2004, 4(4):312-322. [cited by applicant]
Berndsen et al. “New insights into ubiquitin E3 ligase mechanism” Nat. Struct. Mol. Biol. 2014, 21:301-307. [cited by applicant]
Bondeson et al. “Catalytic in vivo protein knockdown by small-molecule PROTACs” Nature Chemical Biology 2015, 11:611-617. [cited by applicant]
Buckley et al. “HaloPROTACS: Use of Small Molecule PROTACS to Induce Degradation of HaloTag Fusion Proteins” ACS Chemical Biology 2015, 10:1831-1837. [cited by applicant]
Buckley et al. “Small-Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System” Angewandte Reviews, 2014, 53:2312-2330. [cited by applicant]
Burkhard et al. “Synthesis and Stability of Oxetane Analogs of Thalidomide and Lenalidomide” Organic Letters 2013, 15(17):4312-4315. [cited by applicant]
C4 Therapeutics Presentation Patel—“Diverse Utility of Targeted Protein Degradation at C4 Therapeutics,” ChemBio, 1 page, Sep. 17, 2017. [cited by applicant]
C4 Therapeutics Presentation Patel—“Advances in the Medicinal Chemistry of Targeted Protein Degradation,” 24 pages, Sep. 27, 2018. [cited by applicant]
C4 Therapeutics Presentation Phillips—“Targeted Protein Degradation,” A new class of small-molecule drugs; applied pharmaceutical chemistry, Cambridge, MA, Apr. 5, 2018; 38 pages. [cited by applicant]
C4 Therapeutics Presentation Phillips—“Small Molecule Driven Targeted Protein Degradation”, ChemBio in the Hub 47, Cambridge, MA, 47 pages (Oct. 22, 2018). [cited by applicant]
C4 Therapeutics Presentation Chrissy Henderson, “Development of AchillesTAG degradation systems and their application to control CAR-T activity,” ChemBio in the Hub, Watertown, MA 1 page (Oct. 22, 2018). [cited by applicant]
C4 Therapeutics Presentation Austin Elam, et al.—“Application of Biophysical Techniques to the Targeted Protein Degradation Therapeutic Strategy” Gibbs BioChem, Cambridge, MA), 1 page, Sep. 24, 2017. [cited by applicant]
C4 Therapeutics Presentation Fisher—“Targeted Protein Degradation”, Targeted Protein Degradation Summit, Boston, MA, 39 pages, Oct. 24-25, 2018. [cited by applicant]
Chamberlain et al. “Structure of the human cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs” Nature Structural and Molecule Biology, 2014, 21(9):803-809. [cited by applicant]
Chang, X. and Stewart, K. A. “What is the functional role of the thalidomide binding protein cereblon?” Int J Biochem Mol Bio. 2011, 2(3):287-294. [cited by applicant]
Contino-Pepin, et al., “Preliminary biological evaluations of new thalidomide analogues for multiple sclerosis application”, Bioorganic & Medicinal Chemistry Letters, 2009, 19(3), 878-881. [cited by applicant]
Corson et al. “Design and applications of bifunctional small molecules: Why two heads are better than one” ACS Chemical Biology 2008, 3(11): 677-692. [cited by applicant]
Crews, C. M. “Targeting the undruggable proteome: the small molecules of my dreams” Chemistry and Biology 2010, 17(6):551-555. [cited by applicant]
Deshaies et al. “Ring domain E3 ubiquitin ligases.” Ann. Rev. Biochem. 2009, 78:399-434. [cited by applicant]
Faden et al. “Generic tools for conditionally altering protein abundance and phenotypes on domain” Biol. Chem. 2014, 395(7-8):737-762. [cited by applicant]
Fischer et al. “Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide” Nature 2014, 512:49-53. [cited by applicant]
Fischer et al. “The Molecular Basis of CRL4DDB2/CSA Ubiquitin Ligase Architecture, Targeting, and Activation,” Cell 2011, 147:1024-1039. [cited by applicant]
Gosink et al. “Redirecting the Specificity of Ubiquitination by Modifying Ubiquitin-Conjugating Enzymes” Proc. Natl. Acad. Sci. USA 1995, 92:9117-9121. [cited by applicant]
International Application No. PCT/US19/35223, filed Jun. 3, 2019; International Search Report and Written Opinion dated Oct. 31, 2019, 10 pages. [cited by applicant]
Ito et al., “Identification of a Primary Target of thalidomide teratogenicity”, Science, 2010, 327(5971), 1345-1350, XP0055062167. [cited by applicant]
Itoh et al. “Protein knockdown using methyl bestatin-ligand hybrid molecules: design and synthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins” Journal of the American C… [cited by applicant]
Jacques et al. “Differentiation of anti-inflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs” PNAS 2015, 112:E1471-E1479. [cited by applicant]
Kronke et al. “Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells” Science 2014, 343(6168):301-305. [cited by applicant]
Kronke et al. “Lenalidomide induces ubiquitination and degradation of CDK1 [alpha] in del(5q) MDS” Nature 2015, 523(7559):183-188. [cited by applicant]
Lai et al. “Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL” Angewandte Chemie International Edition 2016, 55:807-810. [cited by applicant]
Lee et al. “Targeted Degradation of the Aryl Hydrocarbon Receptor by the PROTAC Approach: A Useful Chemical Genetic Tool” ChemBioChem 2007, 8:2058-2062. [cited by applicant]
Liu et al. “Design and biological characterization of hybrid compounds of curcumin and thalidomide for multiple myeloma” Organic and Biomolecular Chemistry 2013, 11:4757. [cited by applicant]
Lu et al. “Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4” Chemistry and Biology 2015, 22(6):755-763. [cited by applicant]
Lu et al. “The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins” Science 2014, 343:305-309. [cited by applicant]
Nawaz et al. “Proteasome-Dependent Degradation of the Human Estrogen Receptor” Proc. Natl. Acad. Sci. USA 1999, 96:1858-1862. [cited by applicant]
Neklesa et al. “Small-molecule hydrophobic tagging-induced degradation of HaloTag fusion proteins.” Nat Chem Biol 2011, 7(8):538-543. [cited by applicant]
Prevet et al. “Microwave-assisted synthesis of functionalized spirohydantoins as 3-D privileged fragments for scouting the chemical space,” Tetrahedron Letters, May 18, 2016, vol. 57, pp. 2888-2894. [cited by applicant]
Pubmed Compound Summary for CID 51072057, Tert-butyl 4-[9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4,4]nonan-7-yl]benzoate, U.S. National Library of Medicine, 3/ May 2011; pp. 1-17; p.… [cited by applicant]
Pubmed Compound Summary for CID 45792656, '7-Cyclopropyl-1,3,7-triazaspiro[4,4]nonane-2m4-dione, U.S. National Library of Medicine, Jun. 21, 2010, pp. 1-13; (https://pubchem.ncbi.nlm.nih.gov/compound/45792656). [cited by applicant]
Pubmed Compound Summary for CID 70731020, '7-(1,2,4)Triazolo[4,3-a]pyridine-3-y1)-2,7-diazaspiro[4,4]nonane-1,3-dione, U.S. National Library of Medicine, Mar. 4, 2013, pp. 1-11; (https://pubchem.ncbi.nlm.nih.gov/compoun… [cited by applicant]
Raina et al. “Chemical Inducers of Targeted Protein Degradation” Journal of Biological Chemistry 2010, 285:11057-11060. [cited by applicant]
Rodriguez-Gonzalez et al. “Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer” Oncogene 2008, 27:7201-7211. [cited by applicant]
Ruchelman et al. “Isosteric analogs of lenalidomide and pomalidomide: Synthesis and biological activity” Bioorganic and Medicinal Chemistry Letters 2012, 23:360-365. [cited by applicant]
Sakamoto et al. “Development of Protacs to Target Cancer-Promoting Proteins for Ubiquitination and Degradation” Molecular and Cellular Proteomics 2003, 2(12):1350-1357. [cited by applicant]
Sakamoto et al. “Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation” PNAS 2001, 98(15):8554-8559. [cited by applicant]
Schneekloth et al. “Chemical approaches to controlling intracellular protein degradation” Chembiochem 2005, 6(1):40-46. [cited by applicant]
Schneekloth et al. “Chemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation” Journal of the American Chemical Society 2004, 126(12):3748-3754. [cited by applicant]
Schneekloth et al. “Targeted Intracellular Protein Degradation Induced by a Small Molecule: En Route to Chemical Proteomics” Bioorganic and Medicinal Chemistry Letters 2008, 18:5904-5908. [cited by applicant]
Shoji, et al., “Modified DNA Aptamer That Binds the (R)-Isomer of a Thalidomide Derivative with High Enantioselectivity”, J. Am. Chem. Soc., 2007, 129, 1456-1464. [cited by applicant]
Spratt et al. “RBR E3 ubiquitin ligases: new structures, new insights, new questions.” Biochem. 2014, 458:421-437. [cited by applicant]
Toure et al. “Small-Molecule PROTACs: New Approaches to Protein Degradation” Angewandte Chemie International Edition 2016, 55:1966-1973. [cited by applicant]
Wang et al. “Roles of F-box proteins in cancer.” Nat. Rev. Cancer 2014, 14:233-347. [cited by applicant]
Winter et al. “Phthalimide conjugation as a strategy for in vivo target protein degradation” Science 2015, 348(6241):1376-1381. [cited by applicant]
Zengerle et al. “Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4” ACS Chem. Biol. 2015, 10:1770-1777. [cited by applicant]
Zhou et al. “Harnessing the Ubiquitination Machinery to Target the Degradation of Specific Cellular Proteins” Molecular Cell 2000, 6:751-756. [cited by applicant]
Database Registry: RN 1413489-08-3, published Dec. 11, 2012. [cited by applicant]
Database Registry: RN 141387-70-3, published Dec. 11, 2012. [cited by applicant]
Database Registry: RN 1413479-09-0, published Dec. 11, 2012. [cited by applicant]
U.S. Pat. No. 11,992,531 B2, U.S. Appl. No. 17/107,781, Philips et al., May 28, 2024. [cited by applicant]
US 2023/0372496 A1, U.S. Appl. No. 18/134,971, Nasveschuk et al., Nov. 23, 2023. [cited by applicant]
US 2023/0416251 A1, U.S. Appl. No. 18/100,992, Nasveschuk et al., Dec. 28, 2023. [cited by applicant]
US 2024/0018118 A1, U.S. Appl. No. 18/134,990, Nasveschuk et al., Jan. 18, 2024. [cited by applicant]
US 2024/0051953 A1, U.S. Appl. No. 17/965,569, Nasveschuk et al., Feb. 15, 2024. [cited by applicant]
US 2024/0076300 A1, U.S. Appl. No. 18/144,800, Nasveschuk et al., Mar. 7, 2024. [cited by applicant]
US 2024/0109889 A1, U.S. Appl. No. 18/370,186, Norcross et al., Apr. 4, 2024. [cited by applicant]
US 2024/0158418 A1, U.S. Appl. No. 18/516,589, Nasveschuk et al., May 16, 2024. [cited by applicant]
U.S. Appl. No. 18/534,395, Nasveschuk et al., filed Dec. 8, 2023. [cited by applicant]
U.S. Appl. No. 18/600,097, Jackson et al., filed Mar. 8, 2024. [cited by applicant]
U.S. Appl. No. 18/642,602, Phillips et al., filed Apr. 22, 2024. [cited by applicant]