Lenvatinib

A summary of the most common chemical descriptors (InChI Key and SMILES codes) for Lenvatinib are summarized together with 3D and 2D structures and relevant physico-chemical properties.

What is the Lenvatinib?

The molecule Lenvatinib presents a molecular formula of C₂₁H₁₉ClN₄O₄ and its IUPAC name is 4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxyquinoline-6-carboxamide.

Lenvatinib (E7080) is an oral multi-targeted receptor tyrosine kinase inhibitor (TKI) that was first approved in Japan in February 2015 for the treatment of unresectable hepatocellular carcinoma (HCC). In the United States, lenvatinib is indicated for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). Lenvatinib has also shown activity in other solid tumors, including renal cell carcinoma (RCC), endometrial cancer, and non-small cell lung cancer (NSCLC)..

The recommended lenvatinib dose in Japan and the United States is 24 mg once daily. The lenvatinib capsule should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal. If a patient vomits or misses a dose, the same dose should not be taken within 4 hours. If more than 4 hours have elapsed, the patient should take the next dose as scheduled. If a patient cannot tolerate the recommended dose, the dose may be reduced..

Lenvatinib is metabolized by CYP3A4 and UGT1A9. Inhibitors or inducers of these enzymes may increase or decrease lenvatinib plasma concentrations, respectively. Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, indinavir, nelfinavir, ritonavir, saquinavir, telithromycin, conivaptan, erythromycin, grapefruit juice) should be avoided. Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) should also be avoided..

The most common lenvatinib side effects (≥20%) are hypertension, fatigue, diarrhea, decreased appetite, nausea, edema, weight decreased, and constipation. Grade 3 or 4 hypertension occurred in 28% of lenvatinib-treated patients in clinical trials. Severe hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg on two consecutive readings at least 4 hours apart) occurred in 5% of patients..

Lenvatinib can also cause QTc prolongation. In clinical trials, QTcF prolongation ≥500 ms occurred in 1% of patients. QTcF prolongation ≥480 ms and <500 ms occurred in 11% of patients. Patients with pre-existing QTc prolongation or other risk factors for QT prolongation and torsade de pointes should be monitored for QT prolongation..

Lenvatinib should be used with caution in patients with renal impairment. The lenvatinib dose should be reduced in patients with moderate or severe renal impairment (estimated creatinine clearance <50 mL/min). Lenvatinib should be avoided in patients with end-stage renal disease on dialysis..

Lenvatinib is a pregnancy category D drug. Women of childbearing potential should be advised to use effective contraception during treatment with lenvatinib and for at least 1 week after the last dose. Men treated with lenvatinib should use effective contraception during treatment and for at least 4 weeks after the last dose..

3D structure

Cartesian coordinates

Geometry of Lenvatinib in x, y and z coordinates (Å units) to copy/paste elsewhere. Generated with Open Babel software.

2D drawing

Molecule descriptors

Other names (synonyms)

IUPAC nomenclature provides a standardized method for naming chemical compounds. Although this system is widely used in chemistry, many chemical compounds have also other names commonly used in different contexts. These synonyms can come from a variety of sources and are used for a variety of purposes.

One common source of synonyms for chemical compounds is the common or trivial names, assigned on the basis of appearance, properties, or origin of the molecule.

Another source of synonyms are historical or obsolete names employed in the past, however replaced nowadays by more modern or standardized names.

In addition to common and historical names, chemical compounds may also have synonyms that are specific to a particular field or industry.

Reference codes for other databases

• CAS number (Chemical Abstracts Service Registry Number) is a unique identifier is assigned to every chemical compound indexed in the CAS database.
• Beilstein: The Beilstein database is a comprehensive source of information on organic chemistry, including information on chemical structures, properties, and reactions. The Beilstein database assigns unique identifiers which can be used to identify compounds in scientific literature and other sources.
• ChEBI (Chemical Entities of Biological Interest): ChEBI is a database of small chemical molecules that are of interest in the field of biology.
• PubChem CID (Compound Identifier): PubChem is a database of chemical compounds that is maintained by the National Institutes of Health (NIH).
• RTECS number (Registry of Toxic Effects of Chemical Substances): The RTECS is a database of information on the toxic effects of chemicals, including information on their structures and properties.
• ChEMBL (Compound Bioactivity Data): ChEMBL is a database of bioactivity data for small molecules, including information on their properties and structures.
• CompTox Dashboard (Environmental Protection Agency): The CompTox Dashboard is a database of information on the toxicology and environmental effects of chemicals.

Physico-Chemical properties

LogP and topological polar surface area (TPSA) values were estimated using Open Babel software.

The n-octanol/water partition coeficient (K_ow) data is applied in toxicology and drug research. K_ow values are used, to guess the environmental fate of persistent organic pollutants. High partition coefficients values, tend to accumulate in the fatty tissue of organisms. Molecules with a log(K_ow) (or LogP) greater than 5 are considered to bioaccumulate.

TPSA values are the sum of the surface area over all polar atoms or molecules, mainly oxygen and nitrogen, also including hydrogen atoms.

In medicinal chemistry, TPSA is used to assess the ability of a drug to permeabilise cells.

For molecules to penetrate the blood-brain barrier (and act on receptors in the central nervous system), TPSA values below 90 Ų are required. Thus, molecules with a polar surface area greater than 140 Ų tend to be poorly permeable to cell membranes.