CC-90009   Click here for help

GtoPdb Ligand ID: 11424

Synonyms: Cereblon modulator 1 | Compound 1 [WO2019006299A1] [1] | compound 16 [PMID: 33591756]
Compound class: Synthetic organic
Comment: CC-90009 is a clinical stage cereblon E3 ligase modulating drug (CELMoD), that targets the G1 to S phase transition 1 (GSPT1, a.k.a. eRF3A) protein for degradation via the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex [2]. Binding of CC-90009 to cereblon alters its conformation, and promotes a change in substrate selectivity away from the transcription factors IKZF1/3 and towards to GSPT1. CC-90009-induced depletion of GSPT1 promotes apoptosis of acute myeloid leukemia (AML) cells via activation of the GCN1/GCN2/ATF4 pathway [3-4].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 95.58
Molecular weight 461.1
XLogP 2.68
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES O=C1CCC(C(=O)N1)N1Cc2c(C1=O)ccc(c2)CNC(=O)C(c1ccc(cc1)Cl)(F)F
Isomeric SMILES O=C1CCC(C(=O)N1)N1Cc2c(C1=O)ccc(c2)CNC(=O)C(c1ccc(cc1)Cl)(F)F
InChI InChI=1S/C22H18ClF2N3O4/c23-15-4-2-14(3-5-15)22(24,25)21(32)26-10-12-1-6-16-13(9-12)11-28(20(16)31)17-7-8-18(29)27-19(17)30/h1-6,9,17H,7-8,10-11H2,(H,26,32)(H,27,29,30)
InChI Key PWBHUSLMHZLGRN-UHFFFAOYSA-N
References
1. Buchholz TJ, Carmichael J, Carrancio S, Fan J, Gupta R, Lu G, Macbeth M, Pace E, Pierce D, Pourdehnad M et al.. (2019)
Compositions and methods of use of 2-(4-chlorophenyl)-n-((2-(2,6-doxopiperidin-3-yl)-1-oxoisoindolin-5-yl) methyl) -2,2-difluoroacetamide.
Patent number: WO2019006299A1. Assignee: Celgene Corporation. Priority date: 30/06/2017. Publication date: 03/01/2019.
2. Hansen JD, Correa M, Alexander M, Nagy M, Huang D, Sapienza J, Lu G, LeBrun LA, Cathers BE, Zhang W et al.. (2021)
CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia.
J Med Chem, 64 (4): 1835-1843. [PMID:33591756]
3. Lopez-Girona A, Lu G, Rychak E, Mendy D, Lu C-C, Rappley I, Fontanillo C, Cathers BE, Daniel TO, Hansen J. (2019)
CC-90009, a Novel Cereblon E3 Ligase Modulator, Targets GSPT1 for Degradation to Induce Potent Tumoricidal Activity Against Acute Myeloid Leukemia (AML).
Blood, 134: 2703. DOI: 10.1182/blood-2019-127892
4. Surka C, Jin L, Mbong N, Lu CC, Jang IS, Rychak E, Mendy D, Clayton T, Tindall E, Hsu C et al.. (2021)
CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells.
Blood, 137 (5): 661-677. DOI: 10.1182/blood.2020008676 [PMID:33197925]