151038-96-9

Basic information

• Product Name: doxorubicin(6-maleimidocaproyl)hydrazone
• Synonyms: doxorubicin(6-maleimidocaproyl)hydrazone;(E)-N'-(1-((2R,4R)-4-((2S,4R,5R,6R)-4-aMino-5-hydroxy-6-Methyltetrahydro-2H-pyran-2-yloxy)-2,5,12-trihydroxy-7-Methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl)-2-hydroxyethylidene)-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanehydrazide;INNO-206;INNO-206 (Aldoxorubicin);DOXO-EMCH;Doxorubicin-EMCH;N'-[(1E)-1-{4-[(3-Amino-2,3,6-trideoxyhexopyranosyl)oxy]-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-2-tetracenyl}-2-hydroxyethylidene]-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexane hydrazide
• CAS NO: 151038-96-9
• Molecular Formula: C₃₇H₄₂N₄O₁₃
• Molecular Weight: 750.74838
• EINECS: 200-258-5
• Mol File: 151038-96-9.mol
• Article Data: 5

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: 1.60
• Refractive Index: 1.708
• Solubility: Soluble in DMSO
• PKA: 7.38±0.60(Predicted)
• CAS DataBase Reference: doxorubicin(6-maleimidocaproyl)hydrazone(CAS DataBase Reference)
• NIST Chemistry Reference: doxorubicin(6-maleimidocaproyl)hydrazone(151038-96-9)
• EPA Substance Registry System: doxorubicin(6-maleimidocaproyl)hydrazone(151038-96-9)

Safety Data

• Safety Statements: 23-24/25
• Hazardous Substances Data: 151038-96-9(Hazardous Substances Data)

Usage

Uses

Doxorubicin-hydrazone-caproyl-maleimide is an albumin-binding prodrug of doxorubicin and a promising clinical candidate for the treatment of a broad range of solid tumors

Biological Activity

the (6-maleimidocaproyl) hydrazone derivative of doxorubicin (inno-206), formerly known as doxo-emch, is a prodrug of the anticancer agent doxorubicin which selectively binds to the cys34 of circulating albumin and accumulates in solid tumors due to passive targeting[1]. inno-206 shows significantly superior antitumor efficacy over free doxorubicin in a spectrum of preclinical tumor models [2].

in vivo

in a murine renal cell carcinoma model and in breast carcinoma xenograft models, inno-206 has shown superior activity over doxorubicin. inno-206 has shown more potent antitumor efficacy than free doxorubicin in the tumor models and is thus a promising clinical candidate for treating a broad range of solid tumors [2].

references

[1]. kratz f. doxo-emch (inno-206): the first albumin-binding prodrug of doxorubicin to enter

InChI:InChI=1/C37H42N4O13/c1-17-32(46)20(38)13-27(53-17)54-22-15-37(51,23(16-42)39-40-24(43)9-4-3-5-12-41-25(44)10-11-26(41)45)14-19-29(22)36(50)31-30(34(19)48)33(47)18-7-6-8-21(52-2)28(18)35(31)49/h6-8,10-11,17,20,22,27,32,42,46,48,50-51H,3-5,9,12-16,38H2,1-2H3,(H,40,43)/b39-23+

Upstream product

• 151038-94-7 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanehydrazide trifluoroacetate 
• 23214-92-8 doxorubicin 
• 25316-40-9 doxorubicin hydrochloride 
• 81186-33-6 N-(ε-maleimidocaproic acid) hydrazide 

Relevant articles and documents

Targeted Delivery of a Ligand-Drug Conjugate via Formyl Peptide Receptor 1 through Cholesterol-Dependent Endocytosis

G protein-coupled receptors (GPCRs) undergo ligand-induced internalization that carries the cognate ligands into intracellular compartments. The present study explores this property for the use of formyl peptide receptor 1 (FPR1), a class A GPCR that binds formylated peptides, as a potential target for drug delivery. A pH-sensitive peptide-drug conjugate consisting of doxorubicin (DOX), N-?-maleimidocaproic acid hydrazide (EMCH), and the formyl peptide fMet-Leu-Phe-Cys (abbreviated as DEF) was prepared. DEF retained pharmacological activities of formyl peptides in binding to FPR1 and mobilization of Ca2+ from intracellular stores. However, the conjugated DOX was no longer cell membrane-permeable and relied on FPR1 for cellular entry. DOX was released from DEF into acidic compartments labeled with fluorescent trackers for endosomes. Treatment of cells with pharmacological inhibitors that block clathrin- or caveolae-mediated endocytosis did not abrogate FPR1-dependent DEF internalization, nor did inhibition of macropinocytosis and phagocytosis. In contrast, cholesterol depletion abrogated DEF internalization through FPR1, suggesting characteristics of cholesterol-dependent uptake mediated by a cell surface receptor. These results demonstrate the possibility of using FPR1 for targeted drug delivery.

Anti-tumor peptide-adriamycin derivative and preparation method thereof as well as anti-tumor drug

The invention relates to the technical field of biomedicines and in particular relates to an anti-tumor peptide-adriamycin derivative and a preparation method thereof as well as an anti-tumor drug. According to the anti-tumor peptide-adriamycin derivative provided by the invention, adriamycin and anti-tumor KLAK peptide are bonded through a hydrazone bond with an acid response property; under a weak acidity environment (with the pH (Potential of Hydrogen) of 5.5 to 6.5) in tumor cells, two anti-cancer drugs (including the adriamycin and the anti-tumor KLAK peptide) are responsively released, the toxic and side effect on normal tissues is reduced and the killing capability to the tumor cells is enhanced, so that the two released anti-cancer drugs exert a cooperative anti-tumor effect through respective action mechanisms and an ideal treatment effect is finally realized.

ALBUMIN BINDING MOLECULES AND USES THEREOF

The invention relates to portable albumin binders, which are useful for improving the pharmacokinetic properties of diagnostic or therapeutic agents, in particular increasing the blood circulation time and/or the tissue penetration capacity of such agents. Molecules of the invention include compounds represented by Formula (1).