Ortataxel Property

Boiling point:

929.7±65.0 °C(Predicted)

Density 

1.36±0.1 g/cm3(Predicted)

solubility 

Soluble in DMSO

pka

11.75±0.46(Predicted)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H331Toxic if inhaled

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P311Call a POISON CENTER or doctor/physician.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

Ortataxel Chemical Properties,Usage,Production

Description

Ortataxel is a novel second-generation taxane, with potent growth inhibitory activity against human cell lines that express P-glycoprotein 170. Compared to paclitaxel and docetaxel, it is 20-30 times more potent as a growth inhibitory agent against human breast and colon tumor cell lines expressing P-gp 170. Ortataxel is also active in NSCL tumor xenografts.

Definition

Ortataxel is a semisynthetic, second-generation taxane derivative with potential antineoplastic activity. Ortataxel binds to and stabilizes tubulin molecules, thereby interfering with the dynamics of microtubule assembly/disassembly. This results in the inhibition of cell division and cellular proliferation. As it represents a poor substrate for P-glycoprotein (P-gp), multi-drug resistance protein (MRP-1) and breast cancer resistance protein (BCRP) mediated efflux, ortataxel modulates multi-drug resistance mechanisms and may be useful for treating multi-drug resistant tumors that express Pgp, MRP-1 and BCRP.

Biological Activity

bay-598 is a aminopyrazoline-based in-vivo probe for smyd2.smyd2 is a catalytic set domain containing protein methyltransferase to monomethylate lysine residues on histone and nonhistone proteins. the overexpression of smyd2 has been found in cancer cell lines and also in various cancer patients.

in vitro

previous data suggest that bay-598 is a peptide-competitive, sam-uncompetitive inhibitor of smyd2 methyltransferase activity, binding to the smyd2 sam substrate complex. bay-598 was tested on a panel of 32 additional methyltransferases, and the results showed that bay-598 displayed >100-fold selectivity for smyd2, with very weak activity for the closest related methyltransferase smyd3. though bay-598 proved to be active for both smyd2 inhibition and par1 antagonism, there was still a greater than 50-fold selectivity for smyd2 relative to par1 [1].

in vivo

in animal study, mice bearing subcutaneous tumor xenografts were orally treated with 10, 30, 70, or 100 mg/kg bay-598 once daily for 3 days. results showed that bay-598 could significantly reduce the methylation with doses starting from 30 mg/kg, with most significant effects in the 100 mg/kg group. treatment with 10 mg/kg bay-598 showed no significant effect on the methylation level, although the exposure at 10 mg/kg was close to the cellular ic50 for about 9 h, indicating an even higher exposure as the ic50 to achieve in-vivo effects [1].

IC 50

27 nm

References

[1] ERIK EGGERT. Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2[J]. Journal of Medicinal Chemistry, 2016, 59 10: 4578-4600. DOI:10.1021/acs.jmedchem.5b01890.
[2] Ortataxel[J]. Definitions, 2020, 97 1. DOI:10.32388/02e3an.
[3] HANS MINDERMAN. Broad-spectrum modulation of ATP-binding cassette transport proteins by the taxane derivatives ortataxel (IDN-5109, BAY 59-8862) and tRA96023.[J]. Cancer Chemotherapy and Pharmacology, 2004, 53 5: 363-369. DOI:10.1007/s00280-003-0745-2.
[4] J. GURTLER. An uncontrolled phase II study evaluating anti-tumor efficacy and safety of ortataxel (BAY 59–8862) in patients with taxane-resistant non-small cell lung cancer[J]. Journal of Clinical Oncology, 2004, 22 1: 7136-7136. DOI:10.1200/JCO.2004.22.90140.7136.