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Development of dual and selective degraders of cyclin-dependent kinases 4 and 6
Open accessAbstract
Cyclin‐dependent kinases 4 and 6 (CDK4/6) are key regulators of the cell cycle, and there are FDA‐approved CDK4/6 inhibitors for treating patients with metastatic breast cancer. However, due to conservation of their ATP‐binding sites, development of selective agents has remained elusive. Here, we report imide‐based degrader molecules capable of degrading both CDK4/6, or selectively degrading either CDK4 or CDK6. We were also able to tune the activity of these molecules against Ikaros (IKZF1) and Aiolos (IKZF3), which are well‐established targets of imide‐based degraders. We found that in mantle cell lymphoma cell lines, combined IKZF1/3 degradation with dual CDK4/6 degradation produced enhanced anti‐proliferative effects compared to CDK4/6 inhibition, CDK4/6 degradation, or IKZF1/3 degradation. In summary, we report here the first compounds capable of inducing selective degradation of CDK4 and CDK6 as tools to pharmacologically dissect their distinct biological functions.
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TL;DR
The paper reports imide-based bifunctional degraders that recruit CRBN to induce dual CDK4/6 degradation or selective degradation of either CDK4 or CDK6, while also tuning IKZF1/3 degradation. In mantle cell lymphoma cell lines, combined CDK4/6 and IKZF1/3 degradation showed enhanced anti-proliferative effects compared with CDK4/6 inhibition, CDK4/6 degradation alone, or IKZF1/3 degradation.
Key findings
- Palbociclib-, ribociclib-, and abemaciclib-based degraders were generated; most maintained biochemical IC50 values of 1–50 nM, and each inhibitor could be converted into active CDK4/6 degraders in Jurkat cells after 4 h treatment with 1 µM.
- Selective degraders were identified: BSJ-01–187 selectively degraded CDK4, YKL-06–102 selectively degraded CDK6, and BSJ-02–162 degraded both CDK4 and CDK6. Analogs BSJ-03–204, BSJ-04–132, and BSJ-03–123 retained dual CDK4/6, selective CDK4, or selective CDK6 degradation, respectively, without degrading IKZF1/3.
- Degradation was CRBN-dependent: in CRISPR/Cas9-generated Crbn−/− Jurkat cells, CDK4/6 and/or IKZF1/3 protein levels were unaffected, and 100 nM BSJ-02–162 induced G1 arrest in wildtype but not Crbn−/− Jurkat cells after 24 h, whereas 100 nM palbociclib induced G1 arrest in both.
- In MCL cells, 1 µM BSJ-02–162 for 1 day degraded CDK4/6 and IKZF1/3, while BSJ-03–204 degraded only CDK4/6; both reduced phosphorylated Rb and induced G1 arrest. BSJ-02–162 showed increased anti-proliferative effects versus BSJ-03–204 in many MCL cell lines. In Molt4 proteomics at 250 nM for 5 h, BSJ-04–132 reduced CDK4 by ~1.9-fold, below the 2-fold threshold, but more than CDK6, IKZF1, and IKZF3.
Methods
- Degraders were designed by attaching PEG or alkyl linkers to the piperazine 4-nitrogen of palbociclib, ribociclib, or abemaciclib, terminating at the 4- or 5-position of thalidomide as the CRBN-recruiting moiety.
- Cellular assays used Jurkat cells (wildtype and Crbn−/−), Molt4 cells, Granta-519 cells, and a panel of MCL cell lines; readouts included enzymatic CDK4/6 kinase inhibition, immunoblotting, propidium iodide cell-cycle analysis, multiplexed mass spectrometry-based proteomics, and anti-proliferative assays.
- Main analyses compared degrader-induced protein loss, CRBN dependence, cell-cycle effects, and proteome-wide selectivity, with a minimum 2-fold change threshold used for proteomic scatterplot depiction.
Limitations
- Stated: structural analysis of kinase-degrader-CRBN ternary complexes will be required to reveal the basis for the observed CDK4 versus CDK6 selectivity.
- Evident: all reported efficacy and degradation data are from cell lines; no in vivo animal or clinical data are reported.
- Evident: the proteomics analysis used a minimum 2-fold change threshold, and CDK4 reduction by BSJ-04–132 (~1.9-fold) did not meet this threshold, so its selective CDK4 degradation was inferred from Table S2 rather than the scatterplot.
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24 Own result · 17 Not checked yet · 6 Own interpretation
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that in mantle cell lymphoma cell lines, combined IKZF1/3 degradation with dual CDK4/6 degradation exhibited enhanced anti-proliferative effects compared to CDK4/6 inhibition, CDK4/6 degradation, or IKZF1/3 degradation.”
- Also stated in: § Abstract · boosted
“We also discovered that simultaneously degrading CDK4/6 and IKZF1/3 demonstrated enhanced anti-proliferation effect in MCL cell lines in comparison to palbociclib, lenalidomide, or a selective CDK4/6 degrader, similar to what was observed with a previously reported BTK degrader that also targeted IKZF1/3[13c].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“In contrast, BSJ-01–187, a ribociclib-based degrader with a 4-carbon alkyl linker, selectively degraded CDK4 (Figure 3C)”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“while the extended PEG-3 linker of the palbociclib-derived compound YKL-06–102 induced selective degradation of CDK6 (Figure 3E).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“For example, BSJ-02–162, which consists of an alkyl linker conjugated to palbociclib, degraded both CDK4 and CDK6 (Figure 3A).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“Here, by varying the linkers for CDK4/6-targeted degraders, we identified molecules capable of acutely and selectively degrading either CDK4 or CDK6.”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The ATP-binding pockets of CDK4 and CDK6 are highly conserved/homologous, and current CDK4/6 inhibitors are approximately equipotent for both proteins, making selective inhibition difficult.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, treatment of Granta-519 cells with these degraders also potently induced a G1 arrest (Figure 6B).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“As expected, BSJ-02–162 induced loss of CDK4/6, IKZF1/3, and other zinc finger proteins known to be recruited to CRBN by imides (Figure 5A)[16].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [16] a An J, Ponthier CM, Sack R, Seebacher J, Stadler MB, Donovan KA, Fischer ES, Nat Commun 2017, 8, 15398; 28530236 PMC5458144 b Sievers QL, Petzold G, Bunker RD, Renneville A, Slabicki M, Liddicoat BJ, Abdulrahman W, Mikkelsen T, Ebert BL, Thoma NH, Science 2018, 362. PMC6326779 30385546
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In the paper
“Subsequently, we found that acute exposure to some degraders differentially affected the abundance of CDK4 and CDK6, as a function of inhibitor, linker length, and linker composition.”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“its non-IKZF1/3-recruiting analog BSJ-03–204 was verified to be selective for CDK4/6 degradation (Figure 5B).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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“none of which induced IKZF1/3 degradation.”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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- Probably not a substantial claim. 6
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In the paper
“Finally, we found that treatment of isogenic Jurkat cells in which CRBN was deleted by CRISPR/Cas9 had no effect on the abundance of CDK4/6 and/or IKZF1/3 protein, demonstrating that that degradation was dependent on CRBN (Figure 3).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“Finally, treatment of Molt4 cells with BSJ-03–123 resulted in loss of CDK6, but not CDK4 or IKZF1/3 (Figure 5D).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“In cells treated with BSJ-04–132, CDK4 (~1.9-fold change) did not meet our minimum 2-fold change threshold to be depicted on the scatterplot (Figure 5C), but its level was reduced to a greater extent than those of CDK6, IKZF1 and IKZF3 (Table S2).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Treatment of Granta-519 cells with 1 µM BSJ-02–162 for 1d resulted in pronounced loss of CDK4/6 and IKZF1/3 protein, while treatment with BSJ-03–204 only resulted in degradation of CDK4/6 (Figure 6A).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, profiling confirmed that we could achieve both dual and selective degradation of CDK4/6 across the proteome after acute compound treatment, and that we could tune degradation of IKZF1/3.”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“found that BSJ-02–162, BSJ-01–187, and YKL-06–102 all induced degradation of IKZF1/3 (Figure 3).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Here, we report imide-based degrader molecules capable of degrading both CDK4/6, or selectively degrading either CDK4 or CDK6.”
- Also stated in: § Abstract · plain
“Here, we generated CRBN-recruiting degraders and identified molecules capable of inducing both dual CDK4/6 and selective CDK4 or CDK6 degradation.”
- Also stated in: § Abstract · plain
“Here, by varying the linkers for CDK4/6-targeted degraders, we identified molecules capable of acutely and selectively degrading either CDK4 or CDK6.”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The ATP-binding pockets of CDK4 and CDK6 are highly conserved/homologous, and current CDK4/6 inhibitors are approximately equipotent for both proteins, making selective inhibition difficult.
- Also stated in: § Abstract · plain
In the paper
“These agents are also currently under investigation in subsets of lung cancers, sarcomas, and lymphomas, such as mantle cell lymphoma (MCL), that exhibits aberrant cell cycle progression via activation of CDK4/6[3].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [3] Sherr CJ, Beach D, Shapiro GI, Cancer Discov 2016, 6, 353– 367. 26658964 PMC4821753 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“As such, CDK4/6 are attractive targets for cancer therapy, and the dual CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib have been FDA approved for treating patients with advanced or metastatic breast cancer, leading to prolonged progression-free-survival[2].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [2] Laderian B, Fojo T, Semin Oncol 2017, 44, 395– 403. 29935901 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, selective degradation of CDK9 was achieved by converting the non-selective CDK inhibitor SNS-032 into a degrader[9].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [9] Olson CM, Jiang B, Erb MA, Liang Y, Doctor ZM, Zhang Z, Zhang T, Kwiatkowski N, Boukhali M, Green JL, Haas W, Nomanbhoy T, Fischer ES, Young RA, Bradner JE, Winter GE, Gray NS, Nat Chem Biol 2018, 14, 163– 170. 29251720 PMC5912898 source
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The small molecule thalidomide, which binds to the ubiquitously expressed E3 ligase substrate adapter Cereblon (CRBN), has often been used as the E3 ligase-binding moiety in degraders[11].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [11] a An S, Fu L, EBioMedicine 2018, 36, 553– 562; 30224312 PMC6197674 b Cromm PM, Crews CM, Cell Chem Biol 2017, 24, 1181– 1190. 28648379 PMC5610075 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“On the other hand, CDK6-specific functions include participating as part of a transcription complex that regulates expression of p16INK4a and VEGF-A[5]”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [5] Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, Schafer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zochbauer-Muller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl R, Busslinger M, Malumbres M, Sexl V, Cancer Cell 2013, 24, 167– 181. 23948297 PMC3743049 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“and acting as a co-factor for NFκB-dependent gene expression[6].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [6] Handschick K, Beuerlein K, Jurida L, Bartkuhn M, Muller H, Soelch J, Weber A, Dittrich-Breiholz O, Schneider H, Scharfe M, Jarek M, Stellzig J, Schmitz ML, Kracht M, Molecular cell 2014, 53, 193– 208. 24389100 source
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These compounds may serve as selective probes for pharmacological dissection of the distinct CDK4 or CDK6 biological functions and as starting points for the development of therapeutic degrader molecules.”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: The ATP-binding pockets of CDK4 and CDK6 are highly conserved/homologous, and current CDK4/6 inhibitors are approximately equipotent for both proteins, making selective inhibition difficult.
In the paper
“CDK4/6 inhibitors are currently being evaluated for MCL, an incurable B cell non-Hodgkin lymphoma whose molecular hallmark is the t(11;14)(q13;q32) chromosomal translocation that juxtaposes CCND1 (encoding cyclin D1) with the Ig heavy chain gene locus, resulting in aberrant cell cycle progression via activation of CDK4/6[17].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [17] Jares P, Colomer D, Campo E, Nat Rev Cancer 2007, 7, 750– 762. 17891190 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“We also recently demonstrated that CDK6, but not CDK4, phosphorylates NFAT family transcription factors to promote T cell activation and enhance the anti-tumor immune response[7].”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [7] Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR, Ivanova E, Paweletz CP, Bowden M, Zhou CW, Herter-Sprie GS, Sorrentino JA, Bisi JE, Lizotte PH, Merlino AA, Quinn MM, Bufe LE, Yang A, Zhang Y, Zhang H, Gao P, Chen T, Cavanaugh ME, Rode AJ, Haines E, Roberts PJ, Strum JC, Richards WG, Lorch JH, Parangi S, Gunda V, Boland GM, Bueno R, Palakurthi S, Freeman GJ, Ritz J, Haining WN, Sharpless NE, Arthanari H, Shapiro GI, Barbie DA, Gray NS, Wong KK, Cancer Discov 2018, 8, 216– 233. 29101163 PMC5809273 source
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In the paper
“In contrast, treatment with 100 nM of BSJ-02–162 for 24h induced G1 arrest in wildtype but not Crbn−/− Jurkat cells, indicating that the cytostatic effect of CDK4/6 degraders required CRBN-dependent degradation of CDK4/6 (Figure 4).”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“High-resolution crystal structures of palbociclib [PDB ID: 5L2I], ribociclib [PDB ID: 5L2T], and abemaciclib [PDB ID: 5L2S] with CDK6 revealed similar binding modes where the aminopyrimidine moiety forms three hydrogen bonds with the backbones of Val101 and Asp163, and the piperazine ring is stabilized via direct interactions with a solvent-exposed ridge consisting of Asp104 and Thr107.”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites PDB ID: 5L2I
- Not checked yetcites PDB ID: 5L2T
- Not checked yetcites PDB ID: 5L2S
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As these effects required the presence of CRBN, they were dependent on target degradation rather than inhibition.”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
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In the paper
“As previous studies indicated that varying the thalidomide aryl amine nitrogen to an oxylamide could prevent recruitment of IKZF1/3 to CRBN[10, 13c]”
§ Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 > Abstract
What the sources say
- Not checked yetcites [10, 13c]
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
The paper relies on this without support.
The ATP-binding pockets of CDK4 and CDK6 are highly conserved/homologous, and current CDK4/6 inhibitors are approximately equipotent for both proteins, making selective inhibition difficult.
“However, due to conservation of their ATP-binding sites, development of selective agents has remained elusive.”
“As current CDK4/6 inhibitors target their highly conserved ATP-binding pockets and are approximately equipotent inhibitors of both proteins, we hypothesized that achieving selectivity would require exploiting selectivity determinants outside of the ATP-binding pocket.”
“The highly homologous ATP-binding pockets of CDK4 and CDK6 has hindered the development of selective CDK4 or CDK6 probes.”
Claims other papers make about this one
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In the citing paper
“Previous studies have shown that a nitrogen to oxygen modification on the thalidomide aryl attachment point can reduce or remove IMiD off-target effects in BTK and CDK4/6 targeted degraders (Dobrovolsky et al., 2019; Jiang et al., 2019).”
From Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development (2020) · cites this paper as Jiang et al., 2019
In the citing paper
“Whereas multiple studies have described numerous CRBN-recruiting dual-selective degraders and CDK6-selective degraders 70–73, none report CDK4-selective degraders; the only reported CDK4-selective degraders are built on a slightly different warhead, ribociclib 74.”
From Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta (2021) · cites this paper as [74]
In the citing paper
“some CRBN-based PROTACs have been shown to degrade the natural substrates of CRBN such as IKZF1 and IKZF3 [86, 87].”
From PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics (2020) · cites this paper as [87]
In the citing paper
“and some CRBNrecruiting PROTACs have been shown to catalyse the degradation of the IMiD targets IKFZ1 and IKFZ3 (refs 40,41 ).”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [41]
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BindingDB Entry 50017954: PROTACs to address the challenges facing small molecule inhibitors.
BindingDB (2023) · UC San Diego · doi:10.7270/q2p55sm1
BindingDB (2021) · UC San Diego · doi:10.7270/q2nz8c6f
BindingDB (2025) · UC San Diego · doi:10.7270/q2ws8zww
BindingDB Entry 50018659: Developments of CRBN-based PROTACs as potential therapeutic agents.
BindingDB (2024) · UC San Diego · doi:10.7270/q27948wc
BindingDB Entry 50008003: Discovery of Selective Small Molecule Degraders of BRAF-V600E.
BindingDB (2021) · UC San Diego · doi:10.7270/q2xd1511
BindingDB (2024) · UC San Diego · doi:10.7270/q26977r0
BindingDB (2021) · UC San Diego · doi:10.7270/q2jw8jf1
BindingDB Entry 50017151: Lessons Learned from Past Cyclin-Dependent Kinase Drug Discovery Efforts.
BindingDB (2023) · UC San Diego · doi:10.7270/q2bv7mpd
BindingDB Entry 50021732: Discovery of First-in-Class PROTAC Degraders of SARS-CoV-2 Main Protease.
BindingDB (2025) · UC San Diego · doi:10.7270/q2wd4563
BindingDB (2023) · UC San Diego · doi:10.7270/q2k93cjv
BindingDB (2022) · UC San Diego · doi:10.7270/q2ks6w6j
BindingDB Entry 50019179: Targeted Protein Degradation Induced by HEMTACs Based on HSP90.
BindingDB (2024) · UC San Diego · doi:10.7270/q2125z03
BindingDB Entry 50015437: Discovery of a Novel BCL-X
BindingDB (2023) · UC San Diego · doi:10.7270/q2nk3jx7
BindingDB Entry 50016327: Selectivity through Targeted Protein Degradation (TPD).
BindingDB (2023) · UC San Diego · doi:10.7270/q22n568r
BindingDB (2021) · UC San Diego · doi:10.7270/q23f4t3t
BindingDB (2021) · UC San Diego · doi:10.7270/q20p13kr
BindingDB (2024) · UC San Diego · doi:10.7270/q2db8660
BindingDB (2024) · UC San Diego · doi:10.7270/q2pv6qt5
BindingDB Entry 50019988: Development of potent and selective degraders of PI5P4Kγ.
BindingDB (2024) · UC San Diego · doi:10.7270/q2mk6j8j
Metadata
- Authors
- Jiang, B., Wang, E. S., Donovan, K. A., Liang, Y., Fischer, E. S., Zhang, T., & Gray, N. S.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Zhang, Tinghu
- Gray, Nathanael S.
- ORCID
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2019-03-29
- Volume
- 58
- Issue
- 19
- Pages
- 6321-6326
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- PMC
- PMC7678623
- OpenAlex
- W2917565897
- Semantic Scholar
- 453a25d8c1f9a6987f549b2e132dc50d712ec85d
- Cited by
- 272
- References
- 24
- Citations by year
- 2026: 19 · 2025: 46 · 2024: 39 · 2023: 26 · 2022: 38 · 2021: 47 · 2020: 43 · 2019: 14
- FWCI
- 12.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Damon Runyon Cancer Research Foundation (DRG-2270-16, DRR-50-18)
- National Institutes of Health (R01CA218278)
- Dana-Farber Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
- Keywords
- CDK4, CDK6, selective degradation, mantle cell lymphoma, metastatic breast cancer, cell cycle regulation, antiproliferative activity
- MeSH terms
- Humans, Imides, Piperazines, Pyridines, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Ikaros Transcription Factor, Cell Cycle Checkpoints
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