Ponatinib

Ponatinib
Clinical data
Pronunciation	/poʊˈnætɪnɪb/ poh-NAT-i-nib
Trade names	Iclusig
Other names	AP24534
AHFS/Drugs.com	Monograph
MedlinePlus	a613029
License data	US DailyMed: Ponatinib;
Pregnancy; category	AU: D;
Routes of; administration	By mouth
ATC code	L01EA05 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	Unknown
Protein binding	>99% (in vitro)
Metabolism	Liver (CYP3A4, 2C8, 2D6, 3A5)
Elimination half-life	12–66 hours
Excretion	Feces (87%), urine (5%)
Identifiers
	IUPAC name 3-(2-Imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide;
CAS Number	943319-70-8;
PubChem CID	24826799;
DrugBank	DB08901;
ChemSpider	24747381;
UNII	4340891KFS;
KEGG	D09950;
ChEBI	CHEBI:78543;
ChEMBL	ChEMBL1171837;
CompTox Dashboard (EPA)	DTXSID50241426 ;
Chemical and physical data
Formula	C29H27F3N6O
Molar mass	532.571 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Cc1ccc(cc1C#Cc2cnc3n2nccc3)C(=O)Nc4ccc(c(c4)C(F)(F)F)CN5CCN(CC5)C;
	InChI InChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39); Key:PHXJVRSECIGDHY-UHFFFAOYSA-N;

Ponatinib, sold under the brand name Iclusig, is a medication used for the treatment of chronic myeloid leukemia and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia.^[4] It was developed by Ariad Pharmaceuticals. It is a multi-targeted tyrosine-kinase inhibitor.^[6] Some forms of chronic myeloid leukemia, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.^[7]

Ponatinib was approved for medical use in the United States in December 2012,^[8] and in the European Union in July 2013.^[5]

^ "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
^ "Product monograph brand safety updates". Health Canada. 7 July 2016. Retrieved 1 April 2024.
^ "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.
^ ^a ^b ^c "Iclusig- ponatinib hydrochloride tablet, film coated". DailyMed. 10 November 2022. Archived from the original on 6 October 2022. Retrieved 11 April 2023.
^ ^a ^b "Iclusig EPAR". European Medicines Agency (EMA). 2 February 2010. Retrieved 20 February 2025.
^ Huang WS, Metcalf CA, Sundaramoorthi R, Wang Y, Zou D, Thomas RM, et al. (June 2010). "Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant". Journal of Medicinal Chemistry. 53 (12): 4701–4719. doi:10.1021/jm100395q. PMID 20513156.
^ O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, et al. (November 2009). "AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance". Cancer Cell. 16 (5): 401–412. doi:10.1016/j.ccr.2009.09.028. PMC 2804470. PMID 19878872.
^ "Drug Approval Package: Iclusig (ponatinib) 15 mg and 45 mg Tablets NDA #203469". U.S. Food and Drug Administration (FDA). 21 December 2012. Archived from the original on 22 February 2017. Retrieved 6 December 2024.

[1] "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.

[2] "Product monograph brand safety updates". Health Canada. 7 July 2016. Retrieved 1 April 2024.

[3] "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.

[Iclusig_FDA_label-4] "Iclusig- ponatinib hydrochloride tablet, film coated". DailyMed. 10 November 2022. Archived from the original on 6 October 2022. Retrieved 11 April 2023.

[Iclusig_EPAR-5] "Iclusig EPAR". European Medicines Agency (EMA). 2 February 2010. Retrieved 20 February 2025.

[pmid20513156-6] Huang WS, Metcalf CA, Sundaramoorthi R, Wang Y, Zou D, Thomas RM, et al. (June 2010). "Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant". Journal of Medicinal Chemistry. 53 (12): 4701–4719. doi:10.1021/jm100395q. PMID 20513156.

[pmid19878872-7] O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, et al. (November 2009). "AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance". Cancer Cell. 16 (5): 401–412. doi:10.1016/j.ccr.2009.09.028. PMC 2804470. PMID 19878872.

[8] "Drug Approval Package: Iclusig (ponatinib) 15 mg and 45 mg Tablets NDA #203469". U.S. Food and Drug Administration (FDA). 21 December 2012. Archived from the original on 22 February 2017. Retrieved 6 December 2024.

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