Drug General Information
Drug ID	D0W5HK
Drug Name	Sorafenib
Synonyms	Nexavar; Sorafenibum; Sorafenib [INN]; Nexavar (TN); Sorafenib (INN); N-[4-Chloro-3-(trifluoromethyl)phenyl]-N'-[4-[2-(N-methylcarbamoyl)-4-pyridyloxy]phenyl]urea; N-(4-Chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea; N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcar bamoyl)-4-pyridyloxy)phenyl)urea; 4(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide; 4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide; 4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonate; 4-(4-{3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide; 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methyl-pyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-2-pyridinecarboxamide; 4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE; Sorafenib (Pan-TK inhibitor)
Drug Type	Small molecular drug
Therapeutic Class	Anticancer Agents
Company	Bayer AG; Onyx Pharmaceuticals
Structure
Drug Resistance Mutations
Target Name	Receptor-type tyrosine-protein kinase (FLT3)				Target Info
Gene Name	FLT3
Uniprot ID	FLT3_HUMAN
Species	Homo sapiens
Reference Sequence	MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESP EDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFDL QNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMENQD ALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNELGRE CTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGNYFEM STYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNSSEDYE IDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPGEYIFHA ENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPNCTEEITE GVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSPGPFPFIQD NISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFYVDFREYEYD LKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKADSSEREALMS ELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREKFHRTWTEIFKE HNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEYENQKRLEEEEDL NVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKICDFGLARDIMSDS NYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGVNPYPGIPVDANFYK LIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGCQLADAEEAMYQNVDG RVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS [Homo sapiens]
Targeted Disease	Leukemia
Drug Resistance Mutations	Mutation info Missense: D835H [1], [2] Mutation Frequency 4 out of 13 patients
	Mutation info Missense: D835Y [1]
	Mutation info Missense: F691L [2] Mutation Frequency 2 out of 6 patients
References
REF 1	Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. Blood. 2012 May 31;119(22):5133-43.
REF 2	Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia. Clin Cancer Res. 2013 Oct 15;19(20):5758-68.

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