Radotinib

• CAT Number: A000101
• CAS Number: 926037-48-1
• Molecular Formula: C27H21F3N8O
• Molecular Weight: 530.515
• Purity: ≥95%
• Synonyms: IY-5511
• Target: Bcl-2 Family
• Solubility: >26.6mg/mL in DMSO
• Storage: Store at -20°C
• IUPAC Name: 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]benzamide
• InChI: InChI=1S/C27H21F3N8O/c1-16-3-4-18(9-23(16)37-26-33-6-5-22(36-26)24-13-31-7-8-32-24)25(39)35-20-10-19(27(28,29)30)11-21(12-20)38-14-17(2)34-15-38/h3-15H,1-2H3,(H,35,39)(H,33,36,37)
• InChIKey: DUPWHXBITIZIKZ-UHFFFAOYSA-N
• SMILES: CC1=C(C=C(C=C1)C(=O)NC2=CC(=CC(=C2)N3C=C(N=C3)C)C(F)(F)F)NC4=NC=CC(=N4)C5=NC=CN=C5

Radotinib, also known as IY-5511, is an orally available, a second-generation tyrosine kinase inhibitor of Bcr-Abl fusion protein and the platelet-derived growth factor receptor (PDGFR), with potential antineoplastic activity. Upon administration, radotinib specifically inhibits the Bcr-Abl fusion protein, an abnormal enzyme expressed in Philadelphia chromosome-positive chronic myeloid leukemia (CML) cells. In addition, this agent also inhibits PDGFR thereby blocking PDGFR-mediated signal transduction pathways.

Reference

1: Eskazan AE, Keskin D. Radotinib and its clinical potential in chronic-phase
chronic myeloid leukemia patients: an update. Ther Adv Hematol. 2017
Sep;8(9):237-243. doi: 10.1177/2040620717719851. Epub 2017 Jul 25. Review. PubMed
PMID: 29051802; PubMed Central PMCID: PMC5639974.

2: Kwak JY, Kim SH, Oh SJ, Zang DY, Kim H, Kim JA, Do YR, Kim HJ, Park JS, Choi
CW, Lee WS, Mun YC, Kong JH, Chung JS, Shin HJ, Kim DY, Park J, Jung CW,
Bunworasate U, Comia NS, Jootar S, Reksodiputro H, Caguioa PB, Lee SE, Kim DW.
Phase III clinical trial (RERISE study) results of Efficacy and safety of
radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid
leukemia. Clin Cancer Res. 2017 Sep 22. pii: clincanres.0957.2017. doi:
10.1158/1078-0432.CCR-17-0957. [Epub ahead of print] PubMed PMID: 28939746.

3: Woo YR, Kim JS, Kim DW, Park HJ. Development of dysplastic nevus during
radotinib therapy in patients with chronic myeloid leukemia. Indian J Dermatol
Venereol Leprol. 2017 Nov-Dec;83(6):704-707. doi: 10.4103/ijdvl.IJDVL_1030_16.
PubMed PMID: 28891531.

4: Heo SK, Noh EK, Kim JY, Jo JC, Choi Y, Koh S, Baek JH, Min YJ, Kim H.
Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia
cells. Eur J Pharmacol. 2017 Jun 5;804:52-56. doi: 10.1016/j.ejphar.2017.03.040.
Epub 2017 Mar 18. PubMed PMID: 28322836.

5: Cheon J, Ahn JW, Park KM, Lee G, Jo YS. Teratogenic Effect of Radotinib: Case
Report. Anticancer Res. 2016 Dec;36(12):6599-6601. Erratum in: Anticancer Res.
2017 Feb;37(2):953. PubMed PMID: 27919989.

6: Heo SK, Noh EK, Gwon GD, Kim JY, Jo JC, Choi Y, Koh S, Baek JH, Min YJ, Kim H.
Radotinib inhibits acute myeloid leukemia cell proliferation via induction of
mitochondrial-dependent apoptosis and CDK inhibitors. Eur J Pharmacol. 2016 Oct
15;789:280-290. doi: 10.1016/j.ejphar.2016.07.049. Epub 2016 Jul 28. PubMed PMID:
27477352.

7: Kim M, Yoon YH, Lee JH, Kim DW, Park HJ. Eruptive Melanocytic Naevi Caused by
Radotinib Therapy in Patients with Chronic Myeloid Leukaemia: 10 cases and a
literature Review. Acta Derm Venereol. 2017 Jan 4;97(1):115-116. doi:
10.2340/00015555-2475. Review. PubMed PMID: 27276507.

8: Noh H, Park MS, Kim SH, Oh SJ, Zang DY, Park HL, Cho DJ, Kim DW, Lee JI.
Optimization of radotinib doses for the treatment of Asian patients with chronic
myelogenous leukemia based on dose-response relationship analyses. Leuk Lymphoma.
2016 Aug;57(8):1856-64. doi: 10.3109/10428194.2015.1113278. Epub 2015 Dec 15.
PubMed PMID: 26666371.

9: Won KH, Jo SY, Lee YJ, Chang SE. Radotinib-induced lentiginosis: a report of
an adverse cutaneous reaction associated with a tyrosine kinase inhibitor. Clin
Exp Dermatol. 2016 Mar;41(2):162-5. doi: 10.1111/ced.12706. Epub 2015 Jul 19.
PubMed PMID: 26190691.

10: Heo SK, Noh EK, Yoon DJ, Jo JC, Choi Y, Koh S, Baek JH, Park JH, Min YJ, Kim
H. Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid
Leukemia Cells. PLoS One. 2015 Jun 12;10(6):e0129853. doi:
10.1371/journal.pone.0129853. eCollection 2015. PubMed PMID: 26065685; PubMed
Central PMCID: PMC4466365.