cemdomespib   Click here for help

GtoPdb Ligand ID: 13726

Synonyms: BIIB-143 | BIIB143 | compound 13b [PMID: 22702513] | compound 3 [PMID: 35905686] | KU-596 | KU596 | RTA 901 | RTA-901
Compound class: Synthetic organic
Comment: Cemdomespib (BIIB143) is an orally bioavailable small molecule modulator of heat shock (molecular chaperone) proteins with neuroprotective activity [4,6]. It contains the same noviose sugar as the antibacterial compound and heat shock protein 90 (Hsp90) C-terminal inhibitor novobiocin, making it a member of the chemical class termed "novologues" or "noviomimetics" [1]. Hsp90 molecular chaperones are regarded as targets for cancer, neurodegenerative diseases and peripheral neuropathies [7]. Inhibition of Hsp90 by novologues increases expression of Hsp70 [2-3,5]. It is this latter mechanism that is proposed to be of therapeutic benefit in treating diabetic peripheral neuropathy.
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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 3
Rotatable bonds 8
Topological polar surface area 97.25
Molecular weight 447.5
XLogP 1.05
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC(=O)NCCC1=CC=C(C=C1C2=CC(=CC=C2)F)O[C@H]3[C@@H]([C@@H]([C@H](C(C)(C)O3)OC)O)O
Isomeric SMILES CC(=O)NCCC1=C(C=C(C=C1)O[C@H]2[C@@H]([C@@H]([C@H](C(O2)(C)C)OC)O)O)C3=CC(=CC=C3)F
InChI InChI=1S/C24H30FNO6/c1-14(27)26-11-10-15-8-9-18(13-19(15)16-6-5-7-17(25)12-16)31-23-21(29)20(28)22(30-4)24(2,3)32-23/h5-9,12-13,20-23,28-29H,10-11H2,1-4H3,(H,26,27)/t20-,21+,22+,23+/m0/s1
InChI Key PDBWOHBMJQOBHL-WBADGQHESA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Anyika M, McMullen M, Forsberg LK, Dobrowsky RT, Blagg BS. (2016)
Development of Noviomimetics as C-Terminal Hsp90 Inhibitors.
ACS Med Chem Lett, 7 (1): 67-71. [PMID:26819668]
2. Ghosh S, Liu Y, Garg G, Anyika M, McPherson NT, Ma J, Dobrowsky RT, Blagg BS. (2016)
Diverging Novobiocin Anti-Cancer Activity from Neuroprotective Activity through Modification of the Amide Tail.
ACS Med Chem Lett, 7 (8): 813-8. [PMID:27563408]
3. Kaur S, Zhang X, Patel S, Rodriguez YA, Luther KJ, Alghafli G, Lang RM, Abrams CK, Dobrowsky RT. (2023)
Pharmacologic Targeting of the C-Terminus of Heat Shock Protein 90 Improves Neuromuscular Function in Animal Models of Charcot Marie Tooth X1 Disease.
ACS Pharmacol Transl Sci, 6 (2): 306-319. [PMID:36798471]
4. Kusuma BR, Zhang L, Sundstrom T, Peterson LB, Dobrowsky RT, Blagg BS. (2012)
Synthesis and evaluation of novologues as C-terminal Hsp90 inhibitors with cytoprotective activity against sensory neuron glucotoxicity.
J Med Chem, 55 (12): 5797-812. [PMID:22702513]
5. Matts RL, Brandt GE, Lu Y, Dixit A, Mollapour M, Wang S, Donnelly AC, Neckers L, Verkhivker G, Blagg BS. (2011)
A systematic protocol for the characterization of Hsp90 modulators.
Bioorg Med Chem, 19 (1): 684-92. [PMID:21129982]
6. Meka PN, Amatya E, Kaur S, Banerjee M, Zuo A, Dobrowsky RT, Blagg BSJ. (2022)
Synthesis and evaluation of 3'- and 4'-substituted cyclohexyl noviomimetics that modulate mitochondrial respiration.
Bioorg Med Chem, 70: 116940. [PMID:35905686]
7. San Gil R, Ooi L, Yerbury JJ, Ecroyd H. (2017)
The heat shock response in neurons and astroglia and its role in neurodegenerative diseases.
Mol Neurodegener, 12 (1): 65. [PMID:28923065]