Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs
Open accessAbstract
Thalidomide was first developed as a sedative around 60 years ago, but exhibited teratogenicity, leading to serious defects such as limb deformities. Nevertheless, thalidomide is now recognized as a therapeutic drug for the treatment of Hansen's disease and myeloma. Immunomodulatory drugs (IMiDs), a new class of anti-cancer drug derived from thalidomide, have also been developed and exert potent anti-cancer effects. Although the molecular mechanism of thalidomide and IMiDs remained unclear for a long time, cereblon, a substrate receptor of the CRL4 E3 ubiquitin ligase was identified as a primary direct target by a new affinity technique. A growing body of evidence suggests that the effect of IMiDs on myeloma and other cancer cells is mediated by CRBN. Each IMiD binds to CRBN and alters the substrate specificity of the CRBN E3 ubiquitin ligase complex, resulting in breakdown of intrinsic downstream proteins such as Ikaros and Aiolos. Here we give an overview of the current understanding of mechanism of action of IMiDs via CRBN and prospects for the development of new drugs that degrade protein of interest.
AI snapshot
Written from the paper’s full text.
TL;DR
This review summarizes how thalidomide and immunomodulatory drugs (IMiDs) act through cereblon (CRBN), a substrate receptor of the CRL4 E3 ubiquitin ligase, rather than through multiple direct targets. Binding of IMiDs to CRBN alters substrate specificity, leading to degradation of neo-substrates such as Ikaros, Aiolos, and, for lenalidomide specifically, Ck1α.
Key findings
- CRBN was identified as a primary direct thalidomide-binding protein using Handa bead affinity purification; only DDB1 and CRBN specifically bound thalidomide, with CRBN binding directly and DDB1 indirectly via complex formation.
- CRBN is a 442-amino-acid protein; thalidomide binds its C-terminal region (339–442), DDB1 binds the intermediate region (187–260), and the glutarimide moiety alone is sufficient for CRBN binding. The S enantiomer of thalidomide binds CRBN more strongly than the R enantiomer.
- IMiDs require CRBN for anti-myeloma effects; lenalidomide and pomalidomide bind CRBN more strongly than thalidomide, and IMiD-induced changes in c-myc, IRF4, and p21 are CRBN-mediated.
- IMiD binding induces degradation of Ikaros (IKZF1) and Aiolos (IKZF3); lenalidomide specifically induces ubiquitination and degradation of Ck1α, explaining its efficacy in del(5q) myelodysplastic syndrome. Human/mouse CRBN homology is 94%, but four amino acids near the thalidomide-binding region differ, and mouse I391 versus human V388 prevents Ck1α degradation in mice.
Methods
- Narrative review of thalidomide/IMiD mechanisms, integrating the authors’ prior biochemical, structural, zebrafish, and chick studies with cited literature.
- Data/sample: no new primary dataset; the review discusses affinity purification with Handa beads, mass spectrometry, recombinant proteins, cell lysates, zebrafish and chick embryos, X-ray crystallography, and published clinical/experimental reports.
- Main analysis: thematic synthesis of findings on CRBN as the direct target, IMiD-induced substrate specificity changes, structural determinants, and species specificity.
Limitations
- The paper states unresolved issues: the CRBN substrate responsible for thalidomide teratogenicity is unknown, as is CRBN’s role in thalidomide’s sedative effects; many questions remain about how IMiD binding induces specific substrates.
- The paper notes concerns for CRBN-based degradation drugs, including off-target protein degradation and interference by internal ligands.
- Evident from the text: this is a narrative review without systematic search criteria, quantitative synthesis, or new experimental data.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 23 cited sources checked · 0 supported · 0 flagged
- Findingcitation
Because the equivalent of V388 of humans is I391 in mice, Ck1α is not degraded in mice.
“it was demonstrated that because the equivalent of V388 of humans is I391 in mice, Ck1α is not degraded in mice [31].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] Jaras M, Miller PG, Chu LP, et al. Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia. J Exp Med. 2014;211:605–12. source
Not checked in the free run.
- Findingown data
CRBN binds to BPA and BPC of DDB1.
“CRBN binds to BPA and BPC.”
Quote in the paperNot a substantial claim - Findingcitation
When lenalidomide binds to CRBN, casein kinase 1a (Ck1α) is specifically ubiquitinated and degraded.
“Ebert and colleagues who previously identified Ikaros and Aiolos reported that when lenalidomide binds to CRBN, casein kinase 1a (Ck1α) is specifically ubiquitinated and degraded [30].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [30] Kronke J, Fink EC, Hollenbach PW, et al. Lenalidomide induces ubiquitination and degradation of Ck1αlpha in del(5q) MDS. Nature. 2015;523:183–8. source
Not checked in the free run.
- Findingown data
Cereblon (CRBN) was identified as a primary direct target of thalidomide by a new affinity technique.
“cereblon, a substrate receptor of the CRL4 E3 ubiquitin ligase was identified as a primary direct target by a new affinity technique.”
- Also stated in: § Cereblon, a direct target of thalidomide · plain
“We concluded that CRBN is a direct target of thalidomide.”
Quote in the paperSubstantial claim - Also stated in: § Cereblon, a direct target of thalidomide · plain
- Findingcitation
Upon binding of IMiDs to CRBN, original substrates (e.g. MEIS2) of CRBN are spared from ubiquitination and degradation, and accumulate.
“It was also found that upon the binding of IMiDs to CRBN, original substrates (e.g.MEIS2) of CRBN are spared from ubiquitination and degradation, and accumulate [32].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] Jadersten M, Saft L, Smith A, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol. 2011;29:1971–9. source
Not checked in the free run.
- Findingown data
The glutarimide moiety of thalidomide on its own is sufficient for its binding to CRBN.
“we demonstrated that the glutarimide moiety (Fig. 1) of thalidomide on its own is sufficient for its binding to CRBN.”
Quote in the paperSubstantial claim - Findingown data
Thalidomide inhibits the autoubiquitination of CRBN.
“we found that thalidomide inhibits the autoubiquitination of CRBN.”
Quote in the paperSubstantial claim - Findingcitation
When lenalidomide binds to CRBN, a new function of CRBN is induced, namely, to ubiquitinate and degrade Ikaros (IKZF1) and Aiolos (IKZF3).
“Ebert's gourp and Kaelin Jr's group independently demonstrated that when lenalidomide binds to CRBN, a new function of CRBN is induced, namely, to ubiquitinate and degrade Ikaros (IKZF1) and Aiolos (IKZF3), which are transcription factors that are known to be responsible for the maturation of B cells [25,26].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [25] Kronke J, Udeshi ND, Narla A, et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2013;343:301–5. source
Not checked in the free run.
- cites [26] Lu G, Middleton RE, Sun H, et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science. 2013;343:305–9. source
Not checked in the free run.
- Findingcitation
In T cells, the ubiquitination and degradation of Ikaros and Aiolos induced by IMiDs leads to enhanced expression of IL-2.
“our group, in collaboration with Celgene, demonstrated that in T cells, the ubiquitination and degradation of Ikaros and Aiolos induced by IMiDs leads to the enhanced expression of IL-2 [27].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Gandhi AK, Kang J, Havens CG, et al. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN). Br J Haematol. 2014;164:811–21. source
Not checked in the free run.
- Findingown data
DDB1 binds to the internal region of CRBN (amino acids 188-248).
“DDB1 was found to bind to the internal region of CRBN (amino acids 188-248), which was consistent with the region identified biochemically, as mentioned above.”
Quote in the paperNot a substantial claim - Findingown data
The S enantiomer of thalidomide binds more strongly to CRBN than the R enantiomer.
“found that the S enantiomer binds more strongly to CRBN than the R enantiomer.”
Quote in the paperNot a substantial claim - Findingcitation
RNAi knockdown of CRBN in multiple myeloma cells results in nearly complete cancellation of the anti-myeloma effects of IMiDs.
“Stewart and colleagues first reported that RNAi knockdown of CRBN in multiple myeloma cells results in nearly complete cancellation of the anti-myeloma effects of IMiDs [23].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Zhu YX, Braggio E, Shi CX, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood. 2011;118:4771–9. source
Not checked in the free run.
- Findingcitation
Lenalidomide and pomalidomide bind more strongly than thalidomide to CRBN.
“demonstrated that lenalidomide and pomalidomide bind more strongly than thalidomide to CRBN [24].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Lopez-Girona A, Mendy D, Ito T, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012;26:2326–35. source
Not checked in the free run.
- Findingcitation
IMiDs, via their glutarimide moiety, become inserted into the tri-Trp pocket composed of three tryptophan residues (W380, W386, and W400) located at the C-terminus of CRBN.
“Both groups concluded that IMiDs, via their glutarimide moiety, become inserted into the tripletryptophan (tri-Trp) pocket composed of three tryptophan residues (W380, W386, and W400) located at the C-teminus of CRBN.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [33] Fischer ES, Bohm K, Lydeard JR, et al. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature. 2014;512:49–53. source
Not checked in the free run.
- cites [34] Chamberlain PP, Lopez-Girona A, Miller K, et al. Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat Struct Mol Biol. 2014;21:803–9. source
Not checked in the free run.
- Findingcitation
Uridine binds to the tri-Trp pocket of CRBN.
“Recently, it was reported that uridine, a component of RNA, binds to the tri-Trp pocket of CRBN [41].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [41] Hartmann MD, Boichenko I, Coles M, Zanini F, Lupas AN. Hernandez Alvarez B. Thalidomide mimics uridine binding to an aromatic cage in cereblon. J Struct Biol. 2014;188:225–32. source
Not checked in the free run.
- Findingcitation
CC-885 induces breakdown of GSPT1 resulting in anti-cancer effects.
“preclinical data suggest that CC-885 induces breakdown of GSPT1 (G1 to S1 phase transition 1) resulting in anti-cancer effects.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] Matyskiela ME, Lu G, Ito T, et al. A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase. Nature. 2016;. doi: 10.1038/nature18611 . source
Not checked in the free run.
- Interpretationreasoning
CRBN functions as a substrate receptor of the CRL4 E3 ubiquitin ligase complex.
“We suggest that CRBN itself functions as a substrate receptor.”
Quote in the paperSubstantial claim - Premisecitation
Lenalidomide exerts highly favorable effects against 5q-syndrome, a type of myelodysplastic syndrome.
“it has been shown that lenalidomide exerts highly favorable effects against 5q-syndrome, a type of myelodysplastic syndrome [28,29].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [28] List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355:1456–65. source
Not checked in the free run.
- cites [29] List A, Kurtin S, Roe DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005;352:549–57. source
Not checked in the free run.
- Interpretationcitation
When Ck1α is further degraded upon lenalidomide treatment, this results in activation of p53 leading to induction of apoptosis.
“When Ck1α was further degraded upon lenalidomide treatment, this resulted in the activation of p53 leading to the induction of apoptosis.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [31] Jaras M, Miller PG, Chu LP, et al. Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia. J Exp Med. 2014;211:605–12. source
Not checked in the free run.
- cites [32] Jadersten M, Saft L, Smith A, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol. 2011;29:1971–9. source
Not checked in the free run.
- Rests on an assumption: In 5q-syndrome, the genetic locus coding for Ck1α is located within the deleted region on chromosome 5.
- Rests on an assumption: In 5q-cells, the expression level of Ck1α is half of that of wild-type cells.
- Interpretationcitation
CRBN is a bona fide target for thalidomide teratogenicity.
“We concluded that CRBN is a bona fide target for thalidomide teratogenicity [19].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] Ito T, Ando H, Suzuki T, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327:1345–50. source
Not checked in the free run.
- Interpretationreasoning
CRBN is essentially required for the anti-cancer effects of IMiDs.
“These results suggest that CRBN is essentially required for the anti-cancer effects of IMiDs.”
Quote in the paperSubstantial claim
- May combine two claims. 7
- Classified as probably not a substantial claim. 1
May combine two claims.
FindingcitationDDB1 binds to the intermediate region (187-260) of CRBN, whereas thalidomide binds to the C-terminus region (339-442).
“DDB1 was found to bind to the intermediate region (187-260) of CRBN, whereas thalidomide was found to bind to the C-terminus region (339-442) [19].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] Ito T, Ando H, Suzuki T, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327:1345–50. source
Not checked in the free run.
May combine two claims.
FindingreasoningIkaros and Aiolos are ubiquitinated and degraded by thalidomide, lenalidomide, and pomalidomide, whereas Ck1α is only ubiquitinated and degraded by lenalidomide.
“Regarding neo-substrates, Ikaros and Aiolos are ubiquitinated and degraded by thalidomide, lenalidomide, and pomalidomide, whereas Ck1α is only ubiquitinated and degraded by lenalidomide, suggesting that there may be unidentified substrates of IMiDs.”
Quote in the paperSubstantial claim- Rests on an assumption: Even when thalidomide is bound to CRBN, the ubiquitination and degradation of Ikaros and Aiolos are weakly induced.
- Rests on an assumption: The ubiquitination and degradation of Ck1α by CRBN is specific to lenalidomide, and thalidomide and pomalidomide do not exhibit this activity.
May combine two claims.
FindingcitationFour amino acids in CRBN around its thalidomide-binding region differ between humans and rodents, and this is responsible for the observed species specificity.
“it was found that four amino acids in CRBN around its thalidomide-binding region differ between humans and rodents, and that this is responsible for the observed species specificity [34].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] Chamberlain PP, Lopez-Girona A, Miller K, et al. Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat Struct Mol Biol. 2014;21:803–9. source
Not checked in the free run.
- Rests on an assumption: The homology between human and mouse CRBN is 94%.
- Rests on an assumption: Thalidomide lacks teratogenicity in rodents.
- Rests on an assumption: The therapeutic effects of IMiDs are hardly detectable in rodents.
May combine two claims.
Findingown dataCRBN binds directly to thalidomide, whereas DDB1 forms a complex with CRBN and hence binds indirectly to thalidomide.
“Binding analyses using affinity beads and DDB1 and CRBN recombinant proteins demonstrated that CRBN binds directly to thalidomide, whereas DDB1 forms a complex with CRBN, and hence binds indirectly to thalidomide.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
FindingcitationGlutamine induces acetylation-dependent breakdown of glutamine synthetase via CRBN.
“More recently, it was reported that glutamine induces acetylation-dependent breakdown of glutamine synthetase via CRBN.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [42] Nguyen TV, Lee JE, Sweredoski MJ, et al. Glutamine triggers acetylation-dependent degradation of glutamine synthetase via the thalidomide receptor cereblon. Mol Cell. 2016;61:809–20. source
Not checked in the free run.
May combine two claims.
FindingcitationIMiDs are effective against diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma, and these effects depend on CRBN.
“IMiDs are now known to be effective against not only multiple myeloma and 5q-syndrome, but also diffuse large B-cell lymphoma (DLBCL), a type of non-Hodgkin lymphoma, as well as mantle cell lymphoma, and these effects are known to also depend on CRBN [37,38].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [37] Yang Y, Shaffer AL, 3rd, Emre NC et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21:723–37. source
Not checked in the free run.
- cites [38] Zhang LH, Kosek J, Wang M, Heise C, Schafer PH, Chopra R. Lenalidomide efficacy in activated B-cell-like subtype diffuse large B-cell lymphoma is dependent upon IRF4 and cereblon expression. Br J Haematol. 2013;160:487–502. source
Not checked in the free run.
May combine two claims.
InterpretationreasoningIMiDs bind a single target (CRBN), and by modulating the substrate specificity of CRBN in numerous ways, IMiDs exert diverse effects.
“these agents appear to bind a single target (CRBN), and by modulating the substrate specificity of CRBN in numerous ways, IMiDs are thought to exert diverse effects (Fig. 4).”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationCRBN controls glutamine metabolism and acetylation is needed for degradation of some substrates of CRBN.
“That study indicated that CRBN controls glutamine metabolism and acetylation is needed for degradation of some substrates of CRBN [42].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [42] Nguyen TV, Lee JE, Sweredoski MJ, et al. Glutamine triggers acetylation-dependent degradation of glutamine synthetase via the thalidomide receptor cereblon. Mol Cell. 2016;61:809–20. source
Not checked in the free run.
The paper relies on this without support.
The homology between human and mouse CRBN is 94%.
“The homology between human and mouse CRBN is 94 %, and because they both bind to thalidomide, it was expected that solving this mystery would be difficult.”
The paper relies on this without support.
In 5q-syndrome, the genetic locus coding for Ck1α is located within the deleted region on chromosome 5.
“In 5q-syndrome, there is a deletion in the long arm of one of the two chromosome 5, resulting in haploinsufficiency; the genetic locus coding for Ck1α is located right within this deleted region.”
The paper relies on this without support.
In 5q-cells, the expression level of Ck1α is half of that of wild-type cells.
“In 5q-cells, the expression level of Ck1α is thus half of that of wild-type cells.”
The paper relies on this without support.
Thalidomide lacks teratogenicity in rodents.
“One long-standing mystery of thalidomide has been its lack of teratogenicity in rodents.”
The paper relies on this without support.
The therapeutic effects of IMiDs are hardly detectable in rodents.
“Even more mysterious was that the therapeutic effects of IMiDs could hardly be detected in rodents.”
The paper relies on this without support.
Even when thalidomide is bound to CRBN, the ubiquitination and degradation of Ikaros and Aiolos are weakly induced.
“Subsequently it was found that even when thalidomide is bound to CRBN, the ubiquitination and degradation of Ikaros and Aiolos are weakly induced, resulting in a new issue.”
The paper relies on this without support.
The ubiquitination and degradation of Ck1α by CRBN is specific to lenalidomide, and thalidomide and pomalidomide do not exhibit this activity.
“It was also found that the ubiquitination and degradation of Ck1α by CRBN is specific to lenalidomide, and that thalidomide and pomalidomide do not exhibit this activity.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Each CRBN modulator acts as a molecular glue that mediates the interaction between CRBN and specific substrates.
“each CRBN modulator acts as a molecular “glue” that mediates the interaction between CRBN and specific substrates16.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [16]
Over a dozen proteins, including Ikaros, Aiolos, GSPT1, CK1α, glutamine synthetase, MEIS2, KCNMA1/SLO1, CLC1, and AMPKα, have been identified as substrates for CRBN.
“To date, over a dozen proteins including Ikaros, Aiolos, GSPT1, CK1α, glutamine synthetase, MEIS2, KCNMA1/SLO1, CLC1, and AMPKα have been identified as substrates for CRBN3,11–16,24–28.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [16]
The transcription factors Ikaros, Aiolos, and MEIS2 are localized to the nucleus.
“The subcellular localizations of these factors differ: the transcription factors Ikaros, Aiolos, and MEIS2 are localized to the nucleus, whereas GSPT1, CK1α, and glutamine synthetase reside in the cytoplasm.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [16]
GSPT1, CK1α, and glutamine synthetase reside in the cytoplasm.
“The subcellular localizations of these factors differ: the transcription factors Ikaros, Aiolos, and MEIS2 are localized to the nucleus, whereas GSPT1, CK1α, and glutamine synthetase reside in the cytoplasm.”
From Genome-wide screening reveals a role for subcellular localization of CRBN in the anti-myeloma activity of pomalidomide (2020) · cites this paper as [16]
The citation lists haven’t been fetched yet
References 45 · Cited by 84
- Authors
- Ito, T., & Handa, H.
- Affiliations
- Tokyo Medical University (JP)
- Corresponding author
- Handa, Hiroshi
- Venue
- International Journal of Hematology
- Published
- 2016-07-26
- Volume
- 104
- Issue
- 3
- Pages
- 293-299
- ISSN
- 0925-5710 (ISSN-L)
- 1865-3774
- OpenAlex
- W2479018367
- Semantic Scholar
- 07e29943bdf6164b1d1f161627fc239cfc66e1af
- Cited by
- 84
- References
- 45
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 16 · 2020: 8 · 2019: 10 · 2018: 10 · 2017: 10 · 2016: 1
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Hematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (26750374)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- cereblon, immunomodulators, thalidomide, CRL4 E3 ubiquitin ligase, Ikaros, Aiolos, multiple myeloma, drug repurposing, protein degradation, mechanism of action, drug target identification
- MeSH terms
- Antineoplastic Agents, Humans, Immunologic Factors, Peptide Hydrolases, Substrate Specificity, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Molecular Targeted Therapy
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