What is the structural formula of Bosutinib?

The chemical name of Bosutinib is 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7- [3-(4-Methylpiperazin-1-yl)propoxy]quinoline-3-carboxonitrile, its molecular formula is C₂₆H₂₉Cl₂N₅O₃, and its molecular weight is 530.45. This molecule is a quinoline tyrosine kinase inhibitor that binds to ABL kinase through a polycyclic aromatic structure to block the signaling pathway. Structurally, bosutinib has higher lipid solubility, which makes it better than some early TKIs in cell membrane penetration, allowing it to reach the site of action more effectively.

From a molecular structure perspective, the core quinoline ring of bosutinib is a key part of its active group, and the piperazine side chain in the molecule gives good pharmacokinetic characteristics and makes the drug more stable in the blood. Compared with first-generation drugs such as imatinib, bosutinib introduces a dichlorophenyl substituent in its structure, which enhances the molecule's affinity for the ABL1 kinase active site. This is also an important reason why it can overcome some drug-resistant mutations.

The three-dimensional structure of bosutinib enables it to fit precisely into the ABL kinase pocket region, forming hydrogen bonds and hydrophobic interactions that prevent ATP binding. Since ATP is the energy source for kinases to function, this blocking mechanism causes downstream signaling pathways (such as STAT5, CrkL, etc.) to be shut down, and abnormal cells lose their ability to divide and are eventually eliminated by apoptosis.

From a pharmaceutical perspective, the structure of bosutinib gives it high selectivity and low cross-resistance. It has strong inhibitory effect onBCR-ABL1 kinase, but has less effect on other kinases such as KIT and PDGFR. This selectivity reduces the risk of non-target side effects. At the same time, researchers also found that its molecular skeleton is highly modifiable, and improved versions of Bosutinib analogs may be derived in the future to improve solubility and bioavailability.

Reference materials:https://go.drugbank.com/drugs/DB06616