WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H200274
CAS#: 220913-32-6
Description: Silatecan (formerly AR-67) is a synthetic, highly lipophilic derivative of camptothecin, with potential antineoplastic and radiosensitizing activities. Silatecan DB-67 binds to and stabilizes the topoisomerase I-DNA covalent complex, inhibiting the religation of topoisomerase I-mediated single-stranded DNA breaks and producing lethal double-stranded DNA breaks when encountered by the DNA replication machinery; inhibition of DNA replication and apoptosis follow. Camptothecin readily undergoes hydrolysis at physiological pH, changing its conformation from the active lactone structure to an inactive carboxylate form.
Hodoodo Cat#: H200274
Name: Silatecan
CAS#: 220913-32-6
Chemical Formula: C26H30N2O5Si
Exact Mass: 478.19
Molecular Weight: 478.610
Elemental Analysis: C, 65.25; H, 6.32; N, 5.85; O, 16.71; Si, 5.87
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Synonym: AR67; AR 67; AR-67; DB67; DB 67; DB-67; 7-t-Butyl-dimethylsilyl-10-hydroxycamptothecin; Silatecan.
IUPAC/Chemical Name: (S)-11-(tert-butyldimethylsilyl)-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
InChi Key: XUSKJHCMMWAAHV-SANMLTNESA-N
InChi Code: 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
SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C([Si](C)(C(C)(C)C)C)C5=CC(O)=CC=C5N=C4C3=C2)=O
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: AR-67(DB-67) is a novel, third-generation camptothecin analogue that has demonstrated high potency in preclinical studies and improved pharmacokinetic properties in humans as compared with first and second-generation products. Arno believes that this unique profile and the potential for oral administration may translate into superior efficacy and patient convenience in the treatment of brain, lung, and other cancers. We believe these advantages could allow DB-67 to become a leading product in the $1.1 billion camptothecin market. Arno is currently conducting a single agent, ascending dose, Phase I clinical study of DB-67 in patients with advanced solid tumors. The study is evaluating the safety of DB-67, establishing the maximum tolerated dose, and characterizing the plasma PK profile.
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The following data is based on the product molecular weight 478.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
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| In vivo protocol: |
1: Cao Y, Tokita MJ, Chen ES, Ghosh R, Chen T, Feng Y, Gorman E, Gibellini F, Ward PA, Braxton A, Wang X, Meng L, Xiao R, Bi W, Xia F, Eng CM, Yang Y, Gambin T, Shaw C, Liu P, Stankiewicz P. A clinical survey of mosaic single nucleotide variants in disease-causing genes detected by exome sequencing. Genome Med. 2019 Jul 26;11(1):48. doi: 10.1186/s13073-019-0658-2. PubMed PMID: 31349857; PubMed Central PMCID: PMC6660700.
2: Liu X, Adane E, Tang F, Leggas M. Pharmacokinetic modeling of the blood-stable camptothecin analog AR-67 in two different formulations. Biopharm Drug Dispos. 2019 Sep;40(8):265-275. doi: 10.1002/bdd.2199. Epub 2019 Jul 28. PubMed PMID: 31292985.
3: Tang F, Tsakalozou E, Arnold SM, Ng CM, Leggas M. Population pharmacokinetic analysis of AR-67, a lactone stable camptothecin analogue, in cancer patients with solid tumors. Invest New Drugs. 2019 Dec;37(6):1218-1230. doi: 10.1007/s10637-019-00744-0. Epub 2019 Feb 28. PubMed PMID: 30820810; PubMed Central PMCID: PMC6713628.
4: Tan R, Cvetkovski B, Kritikos V, Yan K, Price D, Smith P, Bosnic-Anticevich S. Management of allergic rhinitis in the community pharmacy: identifying the reasons behind medication self-selection. Pharm Pract (Granada). 2018 Jul-Sep;16(3):1332. doi: 10.18549/PharmPract.2018.03.1332. Epub 2018 Sep 26. PubMed PMID: 30416632; PubMed Central PMCID: PMC6207357.
5: Lazareva NF, Baryshok VP, Lazarev IM. Silicon-containing analogs of camptothecin as anticancer agents. Arch Pharm (Weinheim). 2018 Jan;351(1). doi: 10.1002/ardp.201700297. Epub 2017 Dec 14. Review. PubMed PMID: 29239010.
6: Burbiel JC, Ghattas W, Küppers P, Köse M, Lacher S, Herzner AM, Kombu RS, Akkinepally RR, Hockemeyer J, Müller CE. 2-Amino[1,2,4]triazolo[1,5-c]quinazolines and Derived Novel Heterocycles: Syntheses and Structure-Activity Relationships of Potent Adenosine Receptor Antagonists. ChemMedChem. 2016 Oct 19;11(20):2272-2286. doi: 10.1002/cmdc.201600255. Epub 2016 Aug 17. PubMed PMID: 27531666.
7: Saeed A, Raana T, Saeed AM, Humayun A. Effect of antenatal depression on maternal dietary intake and neonatal outcome: a prospective cohort. Nutr J. 2016 Jul 11;15(1):64. doi: 10.1186/s12937-016-0184-7. PubMed PMID: 27401187; PubMed Central PMCID: PMC4939634.
8: Carretero MI, Fumuso FG, Neild DM, Giuliano SM, Cetica P, Miragaya MH. Evaluation of the acrosomal status in Lama glama sperm incubated with acrosome reaction inducers. Anim Reprod Sci. 2015 Sep;160:1-11. doi: 10.1016/j.anireprosci.2015.06.014. Epub 2015 Jun 26. PubMed PMID: 26164525.
9: Tsakalozou E, Adane ED, Liang Y, Arnold SM, Leggas M. Protracted dosing of the lipophilic camptothecin analogue AR-67 in non-small cell lung cancer xenografts and humans. Cancer Chemother Pharmacol. 2014 Jul;74(1):45-54. doi: 10.1007/s00280-014-2472-2. Epub 2014 May 8. PubMed PMID: 24807458.
10: Tsakalozou E, Adane ED, Kuo KL, Daily A, Moscow JA, Leggas M. The effect of breast cancer resistance protein, multidrug resistant protein 1, and organic anion-transporting polypeptide 1B3 on the antitumor efficacy of the lipophilic camptothecin 7-t-butyldimethylsilyl-10-hydroxycamptothecin (AR-67) in vitro. Drug Metab Dispos. 2013 Jul;41(7):1404-13. doi: 10.1124/dmd.112.050021. Epub 2013 Apr 25. PubMed PMID: 23620484; PubMed Central PMCID: PMC3684821.
11: Modi S, Xiang TX, Anderson BD. Enhanced active liposomal loading of a poorly soluble ionizable drug using supersaturated drug solutions. J Control Release. 2012 Sep 10;162(2):330-9. doi: 10.1016/j.jconrel.2012.07.001. Epub 2012 Jul 16. PubMed PMID: 22800581.
12: Layton D, Osborne V, Gilchrist A, Shakir SA. Examining the utilization and tolerability of the non-sedating antihistamine levocetirizine in England using prescription-event monitoring data. Drug Saf. 2011 Dec 1;34(12):1177-89. doi: 10.2165/11593930-000000000-00000. PubMed PMID: 22077506.
13: Adane ED, Liu Z, Xiang TX, Anderson BD, Leggas M. Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats. Pharm Res. 2012 Jul;29(7):1722-36. doi: 10.1007/s11095-011-0617-0. Epub 2011 Nov 9. PubMed PMID: 22068278.
14: Horn J, Milewska M, Arnold SM, Leggas M. Metabolic pathways of the camptothecin analog AR-67. Drug Metab Dispos. 2011 Apr;39(4):683-92. doi: 10.1124/dmd.110.037390. Epub 2010 Dec 28. PubMed PMID: 21189330; PubMed Central PMCID: PMC3063719.
15: Tsakalozou E, Horn J, Leggas M. An HPLC assay for the lipophilic camptothecin analog AR-67 carboxylate and lactone in human whole blood. Biomed Chromatogr. 2010 Oct;24(10):1045-51. doi: 10.1002/bmc.1404. PubMed PMID: 20853460; PubMed Central PMCID: PMC2943862.
16: Liukkonen E, Kantola-Sorsa E, Paetau R, Gaily E, Peltola M, Granström ML. Long-term outcome of 32 children with encephalopathy with status epilepticus during sleep, or ESES syndrome. Epilepsia. 2010 Oct;51(10):2023-32. doi: 10.1111/j.1528-1167.2010.02578.x. PubMed PMID: 20477851.
17: Adane ED, Liu Z, Xiang TX, Anderson BD, Leggas M. Factors affecting the in vivo lactone stability and systemic clearance of the lipophilic camptothecin analogue AR-67. Pharm Res. 2010 Jul;27(7):1416-25. doi: 10.1007/s11095-010-0137-3. Epub 2010 Apr 29. PubMed PMID: 20428932.
18: Arnold SM, Rinehart JJ, Tsakalozou E, Eckardt JR, Fields SZ, Shelton BJ, DeSimone PA, Kee BK, Moscow JA, Leggas M. A phase I study of 7-t-butyldimethylsilyl-10-hydroxycamptothecin in adult patients with refractory or metastatic solid malignancies. Clin Cancer Res. 2010 Jan 15;16(2):673-80. doi: 10.1158/1078-0432.CCR-09-2429. Epub 2010 Jan 12. PubMed PMID: 20068096; PubMed Central PMCID: PMC2831464.
19: Schoemaker RG, van Heijningen CL. Bradykinin mediates cardiac preconditioning at a distance. Am J Physiol Heart Circ Physiol. 2000 May;278(5):H1571-6. PubMed PMID: 10775135.
20: Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD. Myocardial protection by brief ischemia in noncardiac tissue. Circulation. 1996 Nov 1;94(9):2193-200. PubMed PMID: 8901671.
