AR-67   Click here for help

GtoPdb Ligand ID: 8919

Synonyms: AR67 | compound 14 [PMID:11052802] | DB-67 | DB67 | silatecan
Compound class: Synthetic organic
Comment: AR-67 is a synthetic, highly lipophilic derivative of the natural alkaloid camptothecin (PubChem CID 24360), with potential antineoplastic [3,5] and radiosensitizing activities [4]. The compound has improved physicochemical properties compared to other camptothecin-derived drugs (e.g. SN-38, the active metabolite of the anti-cancer drug irinotecan, and topotecan) [2].
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 5
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 101.65
Molecular weight 478.19
XLogP 5.09
No. Lipinski's rules broken 1
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 CCC1(O)C(=O)OCc2c1cc1c3nc4ccc(cc4c(c3Cn1c2=O)[Si](C(C)(C)C)(C)C)O
Isomeric SMILES CC[C@@]1(O)C(=O)OCc2c1cc1c3nc4ccc(cc4c(c3Cn1c2=O)[Si](C(C)(C)C)(C)C)O
InChI InChI=1S/C26H30N2O5Si/c1-7-26(32)18-11-20-21-16(12-28(20)23(30)17(18)13-33-24(26)31)22(34(5,6)25(2,3)4)15-10-14(29)8-9-19(15)27-21/h8-11,29,32H,7,12-13H2,1-6H3/t26-/m0/s1
InChI Key XUSKJHCMMWAAHV-SANMLTNESA-N
References
1. Arnold SM, Rinehart JJ, Tsakalozou E, Eckardt JR, Fields SZ, Shelton BJ, DeSimone PA, Kee BK, Moscow JA, Leggas M. (2010)
A phase I study of 7-t-butyldimethylsilyl-10-hydroxycamptothecin in adult patients with refractory or metastatic solid malignancies.
Clin Cancer Res, 16 (2): 673-80. [PMID:20068096]
2. Bom D, Curran DP, Kruszewski S, Zimmer SG, Thompson Strode J, Kohlhagen G, Du W, Chavan AJ, Fraley KA, Bingcang AL et al.. (2000)
The novel silatecan 7-tert-butyldimethylsilyl-10-hydroxycamptothecin displays high lipophilicity, improved human blood stability, and potent anticancer activity.
J Med Chem, 43 (21): 3970-80. [PMID:11052802]
3. Bom D, Curran DP, Zhang J, Zimmer SG, Bevins R, Kruszewski S, Howe JN, Bingcang A, Latus LJ, Burke TG. (2001)
The highly lipophilic DNA topoisomerase I inhibitor DB-67 displays elevated lactone levels in human blood and potent anticancer activity.
J Control Release, 74 (1-3): 325-33. [PMID:11489514]
4. Chen AY, Shih SJ, Garriques LN, Rothenberg ML, Hsiao M, Curran DP. (2005)
Silatecan DB-67 is a novel DNA topoisomerase I-targeted radiation sensitizer.
Mol Cancer Ther, 4 (2): 317-24. [PMID:15713902]
5. Yeh TK, Li CM, Chen CP, Chuu JJ, Huang CL, Wang HS, Shen CC, Lee TY, Chang CY, Chang CM et al.. (2010)
Antitumor activities and pharmacokinetics of silatecans DB-67 and DB-91.
Pharmacol Res, 61 (2): 108-15. [PMID:19643180]