Imatinib

Biological Activity

Imatinib is a number of tyrosine kinase enzymes specific inhibitor. It act by specifically inhibiting a certain enzyme that is characteristic of a particular cancer cell, rather than non-specifically inhibiting and killing all rapidly dividing cells, and served as a model for other targeted therapy modalities through tyrosine kinase inhibition. In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of abl with bcr (breakpoint cluster region), termed bcr-abl. As this is now a constitutively active tyrosine kinase, it is used to decrease bcr-abl activity. It is being used as an experimental agent to suppress platelet-derived growth factor (PDGF) by inhibiting its receptor (PDGF-Rβ).

Product Citations

• 

  BMC Biol. 2021 May 20;19(1):108.

  Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans
  Imatinib purchased from AbMole

• 

  Sci Rep. 2020 Feb 4;10(1):1794.

  A CRISPR/Cas13-based Approach Demonstrates Biological Relevance of Vlinc Class of Long Non-Coding RNAs in Anticancer Drug Response
  Imatinib purchased from AbMole

• 

  Nat Commun. 2019 Dec 20;10(1):5799.

  Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells.
  Imatinib purchased from AbMole

• 

  Biochem Biophys Res Commun. 2019 May 14;512(4):786-792.

  CircRNA_000543 knockdown sensitizes nasopharyngeal carcinoma to irradiation by targeting miR-9/platelet-derived growth factor receptor B axis.
  Imatinib purchased from AbMole

Protocol (for reference only)

Cell Experiment
Cell lines	BON-1 cells and NCI-H727 cells
Preparation method	Seeding BON-1 cells and NCI-H727 cells into flat-bottomed 96-well plates in triplicate and allowing to adhere overnight in 10% fetal bovine serum-supplemented DMEM or RPMI 1640 complete medium, respectively; the medium is then exchanged for serum-free medium (negative control) or serum-free medium containing serial dilutions of Imatinib. Determing the number of metabolically active cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and measuring absorbance in a Packard Spectra microplate reader at 540 nm.after 48 hours (control cultures do not reach confluence), calculating growth inhibition using the following formula: inhibition rate = (1 − a / b) × 100%, where a and b are the absorbance values of the treated and control groups, respectively.
Concentrations	~100 μM
Incubation time	48 hours

Animal Experiment
Animal models	SCLC6, SCLC61, SCLC 74 and SCLC108 small cell lung cancers are injected into Swiss mice (nu/nu, female
Formulation	Imatinib is diluted in water.
Dosages	70 or 100 mg/kg
Administration	Administered via i.p.

Chemical Information

Molecular Weight	493.6
Formula	C29H31N7O
CAS Number	152459-95-5
Solubility (25°C)	DMSO 5 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Philip Cohen, et al. Kinase drug discovery 20 years after imatinib: progress and future directions

[2] Simone Claudiani, et al. The argument for using imatinib in CML

[3] Cornelius F Waller. Imatinib Mesylate

[4] Meinolf Suttorp, et al. Pharmacology and pharmacokinetics of imatinib in pediatric patients

[5] Masatomo Miura. Therapeutic drug monitoring of imatinib, nilotinib, and dasatinib for patients with chronic myeloid leukemia