1. Observe the human tolerance and safety of Combustine for Injection, determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD), and provide a basis for formulating a safe and effective dosing regimen for Phase II clinical trials; 2. Preliminary investigation of the pharmacokinetic behavior and pharmacokinetic parameters of Combustine for Injection in humans; 3. Preliminary evaluation of the efficacy of Combustine for Injection in the treatment of advanced solid tumors.

Start Date07 Sep 2017

Sponsor / Collaborator

Shanghai Huali Bio Pharmaceutical Co. Ltd.

100 Clinical Results associated with Combretastatins A-4

100 Translational Medicine associated with Combretastatins A-4

100 Patents (Medical) associated with Combretastatins A-4

103

Literatures (Medical) associated with Combretastatins A-4

01 Jan 2025·European Journal of Medicinal Chemistry

A novel life for antitumor combretastatins: Recent developments of hybrids, prodrugs, combination therapies, and antibody-drug conjugates

Review

Author: Ammazzalorso, Alessandra ; Amoroso, Rosa ; De Filippis, Barbara ; Fantacuzzi, Marialuigia ; Maccallini, Cristina ; Giampietro, Letizia ; Carradori, Simone

Since their discovery from natural sources, the potent cytotoxic effects of combretastatins were widely studied for the application in antitumor therapy. However, major pharmacokinetic issues as low water solubility and chemical instability of the double bond configuration prevented their use in therapy. A lot of efforts have been directed towards the search of novel strategies, allowing a safer use of combretastatins as anticancer agents. This review analyses the recent landscape in combretastatin research, characterized by the identification of hybrids, prodrugs, and novel combination treatments. Interestingly, the potent cytotoxic agent combretastatin A4 (CA4) was recently proposed as payload in the construction of novel antibody-drug conjugates (ADCs), allowing an efficient targeting of the cytotoxic agent to specific tumors.

01 Jun 2023·Phytochemical Analysis

Chemodiversity of propolis samples collected in various areas of Benin and Congo: Chromatographic profiling and chemical characterization guided by ¹³C NMR dereplication

Article

Author: Le Ray, Anne‐Marie ; Derbré, Séverine ; Azonwade, François ; Blanchard, Patricia ; Goubalan, Elvire ; Boisard, Séverine ; Richomme, Pascal ; Banga‐Mboko, Henri ; Mabanza‐Banza, Balthazar B. ; Bréard, Dimitri ; Baba‐Moussa, Lamine

AbstractIntroductionPropolis is a resinous natural substance collected by honeybees from buds and exudates of various trees and plants; it is widely accepted that the composition of propolis depends on the phytogeographic characteristics of the site of collection.ObjectivesThe aim of this study was to determine the phytochemical composition of ethanolic extracts from eight propolis batches collected in different regions of Benin (north, center, and south) and Congo, Africa.Material and methodsCharacterization of propolis samples was performed by using different hyphenated chromatographic methods combined with carbon‐13 nuclear magnetic resonance (13C NMR) dereplication with MixONat software. Their antioxidant or anti‐advanced glycation end‐product (anti‐AGE) activity was then evaluated by using diphenylpicrylhydrazyl and bovine serum albumin assays, respectively.ResultsChromatographic analyses combined with 13C NMR dereplication showed that two samples from the center of Benin exhibited, in addition to a huge amount of pentacyclic triterpenes, methoxylated stilbenoids or phenanthrenoids, responsible for the antioxidant activity of the extract for the first one. Among them, combretastatins might be cytotoxic. For the second one, the prenylated flavanones known in Macaranga‐type propolis were responsible for its significant anti‐AGE activity. The sample from Congo was composed of many triterpene derivatives belonging to Mangifera indica species.ConclusionTherefore, propolis from the center of Benin seems to be of particular interest, due to its antioxidant and anti‐AGE properties. Nevertheless, as standardization of propolis is difficult in tropical zones due to its great chemodiversity, a systematic phytochemical analysis is required before promoting the use of propolis in food and health products in Africa.

01 Feb 2023·Bioorganic Chemistry

Novel amino analogs of the trimethoxyphenyl ring in potent colchicine site ligands improve solubility by the masked polar group incorporation (MPGI) strategy

Article

Author: Ellahioui, Younes ; Vicente-Blázquez, Alba ; Medarde, Manuel ; Gallego, Laura ; González, Myriam ; Peláez, Rafael ; Álvarez, Raquel

The low aqueous solubility of colchicine site antimitotic agents, of which the trimethoxyphenyl (A ring) is a heavy contributor, is a serious drawback in their clinical development. We have designed new A ring analogs with chameleonic masked polar amino groups able to increase aqueous solubility and also behave as non-polar through intramolecular hydrogen bonds when bound to tubulin. We have incorporated these new A rings in several scaffolds (sulfonamides, combretastatins, phenstatins, isocombretastatins), synthesized, and assayed 43 representatives. The amino analogs show improved aqueous solubility and some of them (8, 60Z, and 67) nanomolar anti-proliferative potencies against human cancer cell lines, with the most favorable substituent being a 3-methylamino group. The antiproliferative effect relates to tubulin inhibition as shown by in vitro tubulin polymerization inhibition, immunofluorescence microscopy, and cell cycle and apoptosis analysis by flow cytometry. The compounds arrest the cell cycle of treated cells in G₂/M and later develop an apoptotic response. Docking studies suggested binding at the colchicine site of tubulin with good agreement with the DFT models of the new structural variations made. The 3-methylamino-4,5‑dimethoxyphenyl moiety is an example of the masked polar group incorporation (MPGI) strategy for soluble ligands binding to hydrophobic sites and a good trimethoxyphenyl ring replacement for the development of new colchicine site ligands.

100 Deals associated with Combretastatins A-4

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 1	CN	Shanghai Huali Bio Pharmaceutical Co. Ltd.	07 Sep 2017

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