86639-52-3

Basic information

• Product Name: 7-Ethyl-10-hydroxycamptothecin
• Synonyms: 7-10-hydroxycamptothecin;(4S)-4,9-Dihydroxy-4,11-diethyl-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione;(4S)-4,9-Dihydroxy-4α,11-diethyl-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione;EHCPT;7-Ethyl-10-hydroxy-CPT (Camptothecine), SN-38;10-Hydroxycamptothecin acetate salt ,99%;Irinotecan Related Compound B (10 mg) ((S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione);(S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
• CAS NO: 86639-52-3
• Molecular Formula: C₂₂H₂₀N₂O₅
• Molecular Weight: 392.4
• EINECS: 1592732-453-0
• Product Categories: Antitumors for Research and Experimental Use;Biochemistry;Natural Plant Extract;Chiral Reagents;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Natural Anti-cancer Medical Materials and It's Derivatives;Pharmaceutical Raw Materials;Miscellaneous Natural Products;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Chiral Reagents, Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals;Inhibitors
• Mol File: 86639-52-3.mol
• Article Data: 44

Chemical Properties

• Melting Point: 217 °C
• Boiling Point: 810.3 °C at 760 mmHg
• Flash Point: 443.8 °C
• Appearance: light-yellow solid
• Density: 1.51 g/cm³
• Refractive Index: 21.5 ° (C=0.2, THF)
• Storage Temp.: −20°C
• Solubility: DMSO: soluble1mg/mL
• PKA: 9.13±0.40(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
• CAS DataBase Reference: 7-Ethyl-10-hydroxycamptothecin(CAS DataBase Reference)
• NIST Chemistry Reference: 7-Ethyl-10-hydroxycamptothecin(86639-52-3)
• EPA Substance Registry System: 7-Ethyl-10-hydroxycamptothecin(86639-52-3)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: 2811
• WGK Germany: 3
• RTECS: UQ0491000
• HazardClass: 6.1
• PackingGroup: Ⅲ
• Hazardous Substances Data: 86639-52-3(Hazardous Substances Data)

Usage

Description

SN-38 (86639-52-3) is the active metabolite of CPT-11 that inhibits DNA topoisomerase I (IC50 values are 0.74 and 1.9 μM in P388 and Ehrlich cells respectively). Inhibits DNA and RNA synthesis (IC50 values are 0.077 and 1.3 μM respectively) but does not affect protein synthesis. SN-38 displays potent antitumor activity against a range of human tumor cell lines (IC50 values are 3.3, 13, 19 and 22 nM for HCT-116, BEL-7402, HL60 and HeLa cells respectively).

Chemical Properties

Light-Yellow Solid

Uses

7-ethyl-10-hydroxycamptothecin (SN 38) is a metabolite of Irinotecan, a DNA topoisomerase inhibitor. SN 38 has been used in trials studying the treatment of Cancer, Advanced Solid Tumors, Small Cell Lung Cancer, Metastatic Colorectal Cancer, and Triple Negative Breast Cancer, among others.

Definition

ChEBI: SN-38 is a member of the class of pyranoindolizinoquinolines that is (4S)-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione bearing two additional ethyl substituents at positions 4 and 11 as well as two additional hydroxy substituents at positions 4 and 9. It is the active metabolite of irinotecan and is ~1000 times more active than irinotecan itself. It has a role as an apoptosis inducer, an EC 5.99.1.2 (DNA topoisomerase) inhibitor, a drug metabolite and an antineoplastic agent. It is a pyranoindolizinoquinoline, a delta-lactone, a tertiary alcohol and a member of phenols.

Biological Activity

Active metabolite of CPT-11 that inhibits DNA topoisomerase I (IC 50 values are 0.74 and 1.9 μ M in P388 and Ehrlich cells respectively). Inhibits DNA and RNA synthesis (IC 50 values are 0.077 and 1.3 μ M respectively) but does not affect protein synthesis. Displays potent antitumor activity against a range of human tumor cell lines (IC 50 values are 3.3, 13, 19 and 22 nM for HCT-116, BEL-7402, HL60 and HELA cells respectively).

References

1) Koizumi et al. (2006), Novel SN-38-incorporating polymeric micelles, NKK012, eradicate vascular endothelial growth factor-secreting bulky tumors; Cancer Res., 66 10048 2) Gao et al. (2005), Synthesis and antitumor activity of the hexacyclic camptothecin derivatives; Bioorg. Med. Chem. Lett., 15 3233 3) Kawato et al. (1991), Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11; Cancer Res., 51 4187

InChI:InChI=1/C20H16N2O5/c1-2-20(26)13-7-15-17-10(6-11-14(21-17)4-3-5-16(11)23)8-22(15)18(24)12(13)9-27-19(20)25/h3-7,23,26H,2,8-9H2,1H3/t20-/m0/s1

Upstream product

• 142677-15-4 SN 38 Carboxylate 
• 35364-15-9 2'-amino-5'-hydroxypropiophenone 
• 110351-94-5 (4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione 
• 16400-32-1 1-bromo-pent-2-yne 
• 99-11-6 citrazinic acid 
• 5398-44-7 2,6-dichloropyridine-4-carboxylic acid 
• 97682-44-5 irinotecan 
• 102978-40-5 4-Ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione 
• 100286-90-6 irinotecan hydrochloirde 
• 113853-66-0 Phosphoric acid mono-((S)-4,11-diethyl-4-hydroxy-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-yl) ester 
• 183433-72-9 5-Benzyloxymethyl-6-methoxy-4-(1-methylene-propyl)-pyridine-2-carboxylic acid propyl ester 
• 183433-67-2 3-Benzyloxymethyl-6-chloro-4-(2-ethyl-[1,3]dioxolan-2-yl)-2-methoxy-pyridine 
• 183434-00-6 propyl (S)-4-ethyl-3,4-dihydro-4-hydroxy-8-methoxy-3-oxo-1H-pyrano[3,4-c]pyridine-6-carboxylate 
• 183434-02-8 propyl (S)-4-ethyl-3,4,7,8-tetrahydro-4-hydroxy-3,8-dioxo-1H-pyrano[3,4-c] pyridine-6-carboxylate 

Downstream Products

• 946062-01-7 7-ethyl-10-O-t-butyldiphenylsilylcamptothecin 
• 97682-44-5 irinotecan 
• 1609283-85-3 C₅₆H₆₂N₄O₁₃ 
• 1609283-87-5 C₄₄H₄₉N₃O₁₁ 
• 1609283-27-3 C₃₅H₃₃N₃O₉ 
• 100286-90-6 irinotecan hydrochloirde 

Relevant articles and documents

On-Demand Activation of a Bioorthogonal Prodrug of SN-38 with Fast Reaction Kinetics and High Releasing Efficiency in Vivo

Although a myriad of bioorthogonal prodrugs have been developed, very few of them present both fast reaction kinetics and complete cleavage. Herein, we report a new bioorthogonal prodrug strategy with both fast reaction kinetics (k2: ～103 M-1 s-1) and complete cleavage (>90% within minutes) using the bioorthogonal reaction pair of N-oxide and boron reagent. Distinctively, an innovative 1,6-elimination-based self-immolative linker is masked by N-oxide, which can be bioorthogonally demasked by a boron reagent for the release of both amino and hydroxy-containing payload in live cells. Such a strategy was applied to prepare a bioorthogonal prodrug for a camptothecin derivative, SN-38, resulting in 10-fold weakened cytotoxicity against A549 cells, 300-fold enhanced water solubility, and on-demand activation upon a click reaction both in vitro and in vivo. This novel bioorthogonal prodrug strategy presents significant advances over the existing ones and may find wide applications in drug delivery in the future.

A stable and cleavable o-linked spacer for drug delivery systems

Anti-cancer chemotherapy with good efficacy and fewer side effects is highly desirable. A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects. The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest. We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug. This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment. This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.

A preparation method of irinotecan hydrochloride (by machine translation)

The invention relates to a preparation method of irinotecan hydrochloride. Its steps are: parent ring to camptothecin as raw material generated by the reaction with the aldehyde 7 - ethyl camptothecin; hydrogen peroxide oxidation then N - oxide - 7 - ethyl camptothecin; by the illumination rearrangement 7 - ethyl - 10 - hydroxy camptothecin; 4 - piperidyl with dimethyl carbonate reaction to produce 4 - piperidyl carbonic acid methyl ester; 7 - ethyl - 10 - hydroxy camptothecin with 4 - piperidyl carbonic acid methyl ester reaction generating irinotecan monomer; irinotecan monomers with hydrochloric salt to obtain the finished product of the irinotecan hydrochloride. Compared with the prior art, the present invention avoid the use of phosgene in the reaction process, chloroform poisonous substance, in production with safe, convenient, less pollution and the like; in addition, the synthetic method avoids the need of the prior process in the defects of the chromatographic column separation and purification, reduces the production cost of the irinotecan, has great economic benefit. (by machine translation)