Mubritinib

Mubritinib

Systematic (IUPAC) name
1-(4-{4-[(2-{(E)-2-[4-(trifluoromethyl)phenyl]ethenyl}-1,3-oxazol-4-yl)methoxy]phenyl}butyl)-1H-1,2,3-triazole
Clinical data
Pregnancy cat.	?
Legal status	Uncontrolled
Routes	Oral
Identifiers
CAS number	366017-09-6
ATC code	None
PubChem	CID 6444692
ChemSpider	4948554
UNII	V734AZP9BR^Y
Chemical data
Formula	C₂₅H₂₃F₃N₄O₂
Mol. mass	468.47 g/mol
SMILES	eMolecules & PubChem

Mubritinib (TAK-165) is a protein kinase inhibitor which was under development by Takeda for the treatment of cancer.^[1]^[2]^[3] It completed phase I clinical trials but appears to have been discontinued, as no new information on the drug has surfaced since December 2008.^[4]

Synthesis

References

^ McCormick, Frank; Doriano Fabbro (2005). Protein Tyrosine Kinases: From Inhibitors to Useful Drugs (Cancer Drug Discovery and Development). Totowa, NJ: Humana Press. ISBN 1-58829-384-X. http://www.springerlink.com/content/k6q2t75544554204/.
^ Mitscher, Lester A.; Lednicer, Daniel (1977). The organic chemistry of drug synthesis. New York: Wiley. ISBN 0-470-10750-2. http://books.google.com/books?id=N6OAhuiHqiIC&lpg=PA108&pg=PA108#v=onepage&q&f=false.
^ Lednicer, Daniel (2008). Strategies for Organic Drug Synthesis and Design. New York: Wiley-Interscience. ISBN 0-470-19039-6. http://books.google.com/books?id=fEwl6Qev-mUC&lpg=PA311&pg=PA311#v=onepage&q&f=false.
^ "Safety and Tolerability Study of TAK-165 in Subjects With Tumors Expressing HER2 - Full Text View - ClinicalTrials.gov". http://clinicaltrials.gov/ct2/show/NCT00034281?term=TAK165&rank=1.

Intracellular chemotherapeutic agents/antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine)

Block microtubule disassembly	Taxanes (Cabazitaxel, Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) • Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	dihydrofolate reductase inhibitor (Aminopterin, Methotrexate, Pemetrexed, Pralatrexate) • thymidylate synthase inhibitor (Raltitrexed, Pemetrexed)

Purine	adenosine deaminase inhibitor (Pentostatin) halogenated/ribonucleotide reductase inhibitors (Cladribine, Clofarabine, Fludarabine) thiopurine (Thioguanine, Mercaptopurine)

Pyrimidine	thymidylate synthase inhibitor (Fluorouracil, Capecitabine, Tegafur, Carmofur, Floxuridine) DNA polymerase inhibitor (Cytarabine) ribonucleotide reductase inhibitor (Gemcitabine) hypomethylating agent (Azacitidine, Decitabine)

Deoxyribonucleotide	ribonucleotide reductase inhibitor (Hydroxycarbamide)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan)

II	Podophyllum (Etoposide, Teniposide)

II+Intercalation	Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin, Pirarubicin, Valrubicin, Zorubicin) • Anthracenediones (Mitoxantrone, Pixantrone)

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Mechlorethamine • Cyclophosphamide (Ifosfamide, Trofosfamide) • Chlorambucil (Melphalan, Prednimustine) • Bendamustine • Uramustine • Estramustine Nitrosoureas: Carmustine • Lomustine (Semustine) • Fotemustine • Nimustine • Ranimustine • Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan, Treosulfan) Aziridines: Carboquone • ThioTEPA • Triaziquone • Triethylenemelamine

Alkylating-like	Platinum (Carboplatin, Cisplatin, Nedaplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin)

Nonclassical	Hydrazines (Procarbazine) • Triazenes (Dacarbazine, Temozolomide) • Altretamine • Mitobronitol

Intercalation	Streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin)

Photosensitizers/PDT

Aminolevulinic acid/Methyl aminolevulinate • Efaproxiral • Porphyrin derivatives (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin)

Other

Enzyme inhibitors	FI (Tipifarnib) • CDK inhibitors (Alvocidib, Seliciclib) • PrI (Bortezomib) • PhI (Anagrelide) • IMPDI (Tiazofurine) • LI (Masoprocol) • PARP inhibitor (Olaparib) • HDAC (Panobinostat, Vorinostat, Romidepsin)

Receptor antagonists	ERA (Atrasentan) • retinoid X receptor (Bexarotene) • sex steroid (Testolactone)

Other/ungrouped	Amsacrine • Trabectedin • retinoids (Alitretinoin, Tretinoin) • Arsenic trioxide • asparagine depleters (Asparaginase/Pegaspargase) • Celecoxib • Demecolcine • Elesclomol • Elsamitrucin • Etoglucid • Lonidamine • HAMLET (human alpha-lactalbumin made lethal to tumor cells) • Lucanthone • Mitoguazone • Mitotane • Oblimersen • Omacetaxine mepesuccinate • mTOR inhibitors (Everolimus, Temsirolimus)

M: NEO

tsoc, mrkr

tumr, epon, para

drug (L1i/1e/V03)

Targeted therapy / extracellular chemotherapeutic agents/antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Cetuximab, Panitumumab) • HER2/neu (Trastuzumab)

Others for solid tumors	EpCAM (Catumaxomab, Edrecolomab) • VEGF-A (Bevacizumab)

Leukemia/lymphoma	lymphoid: CD20 (Ibritumomab, Ofatumumab, Rituximab, Tositumomab), CD30 (Brentuximab), CD52 (Alemtuzumab) myeloid: CD33 (Gemtuzumab)

Tyrosine-kinase inhibitors ("-nib")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Erlotinib, Gefitinib, Vandetanib) • HER1/EGFR and HER2/neu (Afatinib, Lapatinib, Neratinib) RTK class III: C-kit and PDGFR (Axitinib, Pazopanib, Sunitinib, Sorafenib, Toceranib) • FLT3 (Lestaurtinib) VEGFR (Axitinib, Cediranib, Pazopanib, Regorafenib, Semaxanib, Sorafenib, Sunitinib, Toceranib, Vandetanib)

Non-receptor	bcr-abl (Dasatinib, Imatinib, Nilotinib) Src (Bosutinib) Janus kinase (Lestaurtinib, Ruxolitinib) EML4-ALK (Crizotinib)