Name: PROTAC CRABP-II Degrader-3
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

10 mM in DMSO

Appearance

Solid Powder

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

IUPACName

(2E,4E,6E,8E)-9-[(3E)-3-[2-[2-[2-[2-[2-[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoyl]oxyethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]imino-2,6,6-trimethylcyclohexen-1-yl]-3,7-dimethylnona-2,4,6,8-tetraenoic acid

Synonyms

(2E,4E,6E,8E)-9-((E)-3-((((17S,20S,21R)-21-amino-20-hydroxy-17-isobutyl-2,16,19-trioxo-22-phenyl-6,9,12,15-tetraoxa-3,18-diazadocosyl)oxy)imino)-2,6,6-trimethylcyclohex-1-en-1-yl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid; Retinoic acid, 4-[[[(17S,20S,21R)-21-amino-20-hydroxy-17-(2-methylpropyl)-2,16,19-trioxo-22-phenyl-6,9,12,15-tetraoxa-3,18-diazadocos-1-yl]oxy]imino]-, (4E)-; (4E)-4-[[[(17S,20S,21R)-21-Amino-20-hydroxy-17-(2-methylpropyl)-2,16,19-trioxo-22-phenyl-6,9,12,15-tetraoxa-3,18-diazadocos-1-yl]oxy]imino]retinoic acid

Density

1.15±0.1 g/cm3

InChI Key

RZIQIEBBFSSCIQ-KMRDRQGYSA-N

InChI

InChI=1S/C46H68N4O11/c1-32(2)28-40(49-44(55)43(54)38(47)30-36-14-9-8-10-15-36)45(56)60-27-26-59-25-24-58-23-22-57-21-20-48-41(51)31-61-50-39-18-19-46(6,7)37(35(39)5)17-16-33(3)12-11-13-34(4)29-42(52)53/h8-17,29,32,38,40,43,54H,18-28,30-31,47H2,1-7H3,(H,48,51)(H,49,55)(H,52,53)/b13-11+,17-16+,33-12+,34-29+,50-39+/t38-,40+,43+/m1/s1

SMILES

CC1=C(C(CCC1=NOCC(=O)NCCOCCOCCOCCOC(=O)C(CC(C)C)NC(=O)C(C(CC2=CC=CC=C2)N)O)(C)C)C=CC(=CC=CC(=CC(=O)O)C)C

Mechanism

Target: Targets cellular retinoic acid-binding protein II (CRABP-II) for experimental targeted protein degradation studies.

Binding Site: Binds the CRABP-II retinoid-binding cavity and recruited E3 ligase ligand site to support productive ternary complex formation.

Mechanism of Action: PROTAC CRABP-II Degrader-3 is designed for use in PROTAC or targeted protein degradation experiments directed toward cellular retinoic acid-binding protein II (CRABP-II). The bifunctional molecule links a target-recognition element to cereblon, promoting proximity between the protein of interest and ubiquitination machinery. Productive ternary-complex formation can drive polyubiquitination and proteasome-dependent target depletion, allowing researchers to compare pharmacological inhibition with protein removal. It is suitable for evaluating degradation potency, kinetics, pathway selectivity, and downstream signaling consequences in engineered or disease-relevant cellular models.

Applications

• PROTAC-Mediated Protein Degradation: PROTAC CRABP-II Degrader-3 is a powerful tool for studying the targeted degradation of cellular retinoic acid-binding protein II (CRABP-II). By inducing the ubiquitination and subsequent proteasomal degradation of CRABP-II, researchers can investigate its role in retinoic acid signaling pathways and its implications in cellular differentiation.

• Targeted Degradation in Cancer Research: This degrader is instrumental in exploring the therapeutic potential of selectively degrading CRABP-II in cancer cells. By reducing CRABP-II levels, researchers can assess its contribution to tumor growth and progression, providing insights into novel cancer treatment strategies based on protein degradation.

• Mechanistic Studies of PROTACs: PROTAC CRABP-II Degrader-3 serves as a model compound for elucidating the mechanisms of PROTAC-mediated protein degradation. By examining its interaction with the ubiquitin-proteasome system, scientists can gain a deeper understanding of the factors influencing the efficiency and selectivity of PROTACs in targeted protein degradation.

• Drug Discovery and Development: Utilizing this degrader in drug discovery pipelines allows researchers to identify and validate new targets for PROTAC-based therapies. By observing the effects of CRABP-II degradation, scientists can uncover potential pathways for intervention, advancing the development of next-generation therapeutics.

1. Protein knockdown using methyl bestatin-ligand hybrid molecules: design and synthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins.

Itoh, Y., Ishikawa, M., Naito, M. and Hashimoto, Y., 2010. Journal of the American Chemical Society, 132(16), pp.5820-5826.

Induction of selective degradation of target proteins by small molecules (protein knockdown) would be useful for biological research and treatment of various diseases. To achieve protein knockdown, we utilized the ubiquitin ligase activity of cellular inhibitor of apoptosis protein 1 (cIAP1), which is activated by methyl bestatin (MeBS, 2). We speculated that formation of an artificial (nonphysiological) complex of cIAP1 and a target protein would be induced by a hybrid molecule consisting of MeBS (2) linked to a ligand of the target protein, and this would lead to cIAP1-mediated ubiquitination and subsequent proteasomal degradation of the target protein. To verify this hypothesis, we focused on cellular retinoic acid-binding proteins (CRABP-I and -II) and designed hybrid molecules (compounds 4) consisting of MeBS (2) coupled via spacers of various lengths to all-trans retinoic acid (ATRA, 3), a ligand of CRABPs. Compounds 4 induced selective loss of CRABP-I and -II proteins in cells. We confirmed that 4b induced formation of a complex of cIAP1 and CRABP-II in vitro and induced proteasomal degradation of CRABP-II in cells. When neuroblastoma IMR-32 cells were treated with 4b, the level of CRABP-II was reduced and cell migration was inhibited, suggesting potential value of CRABP-II-targeting therapy for controlling tumor metastasis. Our results indicate that 4b possesses sufficient activity, permeability, and stability in cells to be employed in cellular assays. Hybrid molecules such as 4 should be useful not only as chemical tools for studying the biological/physiological functions of CRABPs but also as candidate therapeutic agents targeting CRABPs.

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It is commonly abbreviated as: C₁V₁ = C₂V₂