-
Bioinformation 2020Lipocalin 2 (Lcn2, also called as neutrophil gelatinase-associated lipocalin) is a member of the lipocalin family and a known target for breast cancer. Therefore, it is...
Lipocalin 2 (Lcn2, also called as neutrophil gelatinase-associated lipocalin) is a member of the lipocalin family and a known target for breast cancer. Therefore, it is of interest to use Docetaxel as a scaffold to design molecules with improved efficiency from naturally derived phytochemicals. We document 10 analogues (4Deacetyltaxol, 7Acetyltaxol, Cabazitaxel, Cephalomannine, Docetaxal, Deacetyltaxol, Docetaxeltrihydrate, Ortataxel, Paclitaxel, Taxoline) having optimal binding with Lipocalin 2 in comparison with Docetaxel. This data is highly useful for consideration in the design and development of drugs for breast cancer.
PubMed: 32884206
DOI: 10.6026/97320630016438 -
Clinical Investigation 2013The oral taxanes are analogues of existing taxanes with a possible broad range of antitumor activity. They also have the potential advantages of ease of administration,...
The oral taxanes are analogues of existing taxanes with a possible broad range of antitumor activity. They also have the potential advantages of ease of administration, better efficacy and lesser toxicity than currently available taxanes. These drugs have been used in several Phase I clinical trials, the methodology and results of which will be reviewed here.
PubMed: 26146540
DOI: 10.4155/cli.13.18 -
Molecular BioSystems Oct 2012The effects on tubulin dynamics of paclitaxel, ortataxel and two recently developed taxol derivatives bearing a five-membered heterocyclic ring fused at the 1,14...
The effects on tubulin dynamics of paclitaxel, ortataxel and two recently developed taxol derivatives bearing a five-membered heterocyclic ring fused at the 1,14 position were analysed by means of molecular dynamic simulations and the MM-PBSA approach. Tubulin polymerization kinetics and microtubule morphology assays were also conducted, providing support to computational results. In particular, it has been shown that the two recently developed 1,14-heterofused taxanes IDN5839 and IDN5798 are able to speed up the in vitro tubulin assembly by promoting the nucleation phase and to affect the microtubule network in cells earlier than paclitaxel.
Topics: Bridged-Ring Compounds; Cell Line, Tumor; Computational Biology; Humans; Kinetics; MCF-7 Cells; Microtubules; Models, Molecular; Molecular Dynamics Simulation; Paclitaxel; Protein Binding; Protein Conformation; Protein Multimerization; Taxoids; Tubulin
PubMed: 23073462
DOI: 10.1039/c2mb25326g -
Zeitschrift Fur Naturforschung. C,... 2009In order to find the minimal structural requirements to maintain microtubule binding, 12 taxol analogues have been docked to the taxol binding site of tubulin. By...
In order to find the minimal structural requirements to maintain microtubule binding, 12 taxol analogues have been docked to the taxol binding site of tubulin. By comparing the interactions of each analogue with beta-tubulin, the structure-activity relationships are summarized as follow: C-2 benzoyl and taxane ring systems are the essential groups for microtubule binding, the improvements of bioactivity and bioavailability are dependent on the substituents at positions C-1, C-4, C-7, C-9, C-10, and C-14, whereas the C-13 side chain mainly provides a specific binding.
Topics: Binding Sites; Bridged-Ring Compounds; Docetaxel; Kinetics; Microtubules; Models, Molecular; Paclitaxel; Structure-Activity Relationship; Taxoids; Thermodynamics; Tubulin
PubMed: 19791508
DOI: 10.1515/znc-2009-7-814 -
IUBMB Life 2002P-glycoprotein (P-GP)-based multidrug resistance (MDR) and undesirable side effects are significant drawbacks to the clinical use of paclitaxel and docetaxel. Extensive... (Review)
Review
P-glycoprotein (P-GP)-based multidrug resistance (MDR) and undesirable side effects are significant drawbacks to the clinical use of paclitaxel and docetaxel. Extensive SAR studies of taxanes in these laboratories led to the discovery of new generation taxanes that are highly active against not only drug-sensitive but also drug-resistant human cancer cell lines as well as tumor xenografts in mice. One of these second generation taxanes, SB-T-110131 (IDN5109), exhibited excellent pharmacological profile in the preclinical studies and has been selected for clinical development (recoded as Bay 59-8862), which is currently in the phase II clinical trials. Bay 59-8862 is orally active with high bioavailability, showing excellent activity against a variety of drug-resistant tumors. "Advanced second generation taxanes" show essentially no difference in cytotoxicity against drug-resistant and drug-sensitive cell lines, virtually overcoming MDR. Photoaffinity labeling of P-GP using photoreactive radiolabeled paclitaxel analogs has disclosed the paclitaxel-binding domain of P-GP. Highly efficient taxane-based MDR reversal agents (TRAs) have also been developed, which can recover the cytotoxicity of paclitaxel to practically the original level against paclitaxel-resistant MDR expressing cancer cells. Highly promising results have emerged from the study of taxane-monoclonal antibody (MAb) immunoconjugates, which have been proved to specifically deliver extremely cytotoxic agents to tumor in an animal model.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Animals; Antibodies, Monoclonal; Antineoplastic Agents; Binding Sites; Bridged-Ring Compounds; Clinical Trials as Topic; Drug Resistance, Multiple; Humans; Mice; Models, Chemical; Models, Molecular; Neoplasm Transplantation; Paclitaxel; Protein Structure, Tertiary; Taxoids
PubMed: 12121008
DOI: 10.1080/15216540212658 -
Bulletin Du Cancer Apr 2002This review describes the experimental and clinical properties of new taxanes and epothilones. Six new taxanes are currently in clinical trials: BMS 184476, BMS 188797,... (Review)
Review
This review describes the experimental and clinical properties of new taxanes and epothilones. Six new taxanes are currently in clinical trials: BMS 184476, BMS 188797, BMS 275183, IDN 5109/BAY 598862, RPR 109881A et RPR 116258 All these derivatives share the same feature which is a decreased recognition by Pgp-170, the product of the MDR1 gene. This confers innovative properties such as in vitro and in vivo activities on tumors expressing the Pgp-170, activity by the oral route. Identification of other families of molecules bearing the same mechanism of action as taxol has been a goal pursued by many groups. The discovery of epothilones led to the pharmaceutical development of two molecules: EPO 906 (which corresponds to the natural compound epothilone B) and BMS 247550. Phase I clinical trials have established that all these investigational drugs (taxanes and epothilones) can be safely administered in patients, the limiting toxicity being most of the time febrile neutropenia. Many tumor responses have been noted.
Topics: Animals; Antineoplastic Agents, Phytogenic; Bridged-Ring Compounds; Clinical Trials, Phase I as Topic; Drug Screening Assays, Antitumor; Humans; Mice; Neutropenia; Paclitaxel; Taxoids
PubMed: 12016034
DOI: No ID Found