axitinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	4225	319460-85-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: axitinib inlyta AG 013736 AG-013736	A benzamide and indazole derivative that acts as a TYROSINE KINASE inhibitor of the VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR. It is used in the treatment of advanced RENAL CELL CARCINOMA. Molecular weight: 386.47 Formula: C22H18N4OS CLOGP: 3.33 LIPINSKI: 0 HAC: 5 HDO: 2 TPSA: 70.67 ALOGS: -5.85 ROTB: 5 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Hosey CM, Chan R, Benet LZ
CL (Clearance)	5 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.00 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	4.30 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Jan. 27, 2012	FDA	PFIZER

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	342.66	27.02	168	4235	91132	46590527
Neoplasm progression	282.99	27.02	103	4300	26580	46655079
Renal cancer	248.25	27.02	58	4345	3110	46678549
Diarrhoea	214.04	27.02	261	4142	559341	46122318
Metastatic renal cell carcinoma	173.63	27.02	35	4368	928	46680731
Death	167.10	27.02	180	4223	335368	46346291
Hypertension	143.29	27.02	130	4273	196226	46485433
Renal cell carcinoma	119.06	27.02	33	4370	3505	46678154
Palmar-plantar erythrodysaesthesia syndrome	105.24	27.02	47	4356	20404	46661255
Decreased appetite	101.25	27.02	107	4296	193729	46487930
Dysphonia	93.10	27.02	53	4350	38361	46643298
Hypothyroidism	77.97	27.02	44	4359	31294	46650365
Stomatitis	71.83	27.02	56	4347	68241	46613418
Blood pressure increased	67.89	27.02	71	4332	126595	46555064
Fatigue	46.71	27.02	144	4259	608553	46073106
Posterior reversible encephalopathy syndrome	39.64	27.02	22	4381	15119	46666540
Dehydration	38.27	27.02	60	4343	159480	46522179
Weight decreased	38.27	27.02	70	4333	210779	46470880
Renal cancer metastatic	35.83	27.02	8	4395	348	46681311
Oligodipsia	32.56	27.02	5	4398	24	46681635
Oral pain	31.96	27.02	23	4380	24774	46656885
Proteinuria	27.60	27.02	18	4385	16535	46665124
Drug ineffective	27.46	27.02	15	4388	677823	46003836

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	1060.18	20.46	538	10637	79336	29861967
Renal cancer	650.37	20.46	173	11002	3867	29937436
Neoplasm progression	630.76	20.46	241	10934	17782	29923521
Dysphonia	530.73	20.46	216	10959	18816	29922487
Diarrhoea	413.16	20.46	559	10616	333544	29607759
Metastatic renal cell carcinoma	378.57	20.46	102	11073	2390	29938913
Renal cell carcinoma	345.30	20.46	115	11060	5651	29935652
Death	335.00	20.46	525	10650	356758	29584545
Hypertension	305.99	20.46	295	10880	121059	29820244
Palmar-plantar erythrodysaesthesia syndrome	230.63	20.46	112	11063	14758	29926545
Fatigue	181.89	20.46	380	10795	320293	29621010
Decreased appetite	142.62	20.46	223	10952	149687	29791616
Blood pressure increased	122.02	20.46	142	11033	71786	29869517
Hypothyroidism	102.77	20.46	66	11109	14897	29926406
Neoplasm malignant	96.95	20.46	68	11107	17746	29923557
Aphonia	93.09	20.46	37	11138	3007	29938296
Stomatitis	92.23	20.46	90	11085	37189	29904114
Drug ineffective	76.36	20.46	17	11158	340370	29600933
Renal cancer metastatic	71.42	20.46	20	11155	541	29940762
Oral pain	60.66	20.46	40	11135	9429	29931874
Second primary malignancy	53.68	20.46	32	11143	6324	29934979
Weight decreased	51.71	20.46	148	11027	150773	29790530
Proteinuria	51.59	20.46	45	11130	16100	29925203
Glossodynia	48.12	20.46	24	11151	3337	29937966
Malignant urinary tract neoplasm	47.83	20.46	8	11167	12	29941291
Toxicity to various agents	43.55	20.46	7	11168	177176	29764127
Neutropenia	31.74	20.46	5	11170	128535	29812768
Blood thyroid stimulating hormone increased	31.16	20.46	17	11158	2839	29938464
Thyroid disorder	29.18	20.46	16	11159	2698	29938605
Therapy interrupted	28.68	20.46	19	11156	4510	29936793
Nausea	28.10	20.46	198	10977	296759	29644544
Oral discomfort	24.57	20.46	14	11161	2542	29938761
Febrile neutropenia	24.49	20.46	5	11170	106688	29834615
Blister	24.17	20.46	34	11141	20649	29920654
Posterior reversible encephalopathy syndrome	23.35	20.46	22	11153	8685	29932618
Constipation	22.89	20.46	93	11082	112813	29828490
Pain in extremity	22.52	20.46	91	11084	110130	29831173
Renal cell carcinoma stage IV	22.07	20.46	5	11170	55	29941248
Dry skin	22.04	20.46	34	11141	22420	29918883
Nephrotic syndrome	21.60	20.46	19	11156	6866	29934437
Drug interaction	21.21	20.46	26	11149	199542	29741761
Dysgeusia	20.85	20.46	35	11140	24766	29916537
Clear cell renal cell carcinoma	20.64	20.46	9	11166	922	29940381
Dehydration	20.64	20.46	96	11079	123443	29817860

Pharmacologic Action:

Source	Code	Description
ATC	L01EK01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors
FDA MoA	N0000020000	Receptor Tyrosine Kinase Inhibitors
FDA EPC	N0000175605	Kinase Inhibitor
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D047428	Protein Kinase Inhibitors
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:38637	tyrosine kinase inhibitors
CHEBI has role	CHEBI:65207	vegfr inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Renal cell carcinoma	indication	702391001	DOID:4450

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.57	acidic
pKa2	12.18	acidic
pKa3	4.85	Basic
pKa4	1.98	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Vascular endothelial growth factor receptor 3	Kinase	P35916	VGFR3_HUMAN	INHIBITOR	Kd	6.77		CHEMBL	CHEMBL
Vascular endothelial growth factor receptor 1	Kinase	P17948	VGFR1_HUMAN	INHIBITOR	Kd	8.24		CHEMBL	CHEMBL
Vascular endothelial growth factor receptor 2	Kinase	P35968	VGFR2_HUMAN	INHIBITOR	Kd	8.23		CHEMBL	CHEMBL
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN		Kd	7.51		CHEMBL
Cyclin-dependent kinase-like 2	Kinase	Q92772	CDKL2_HUMAN		Kd	6.28		CHEMBL
Epidermal growth factor receptor	Kinase	P00533	EGFR_HUMAN		Kd	5.64		CHEMBL
Fibroblast growth factor receptor 3	Kinase	P22607	FGFR3_HUMAN		Kd	6.68		CHEMBL
SRSF protein kinase 1	Kinase	Q96SB4	SRPK1_HUMAN		Kd	5.74		CHEMBL
Platelet-derived growth factor receptor alpha	Kinase	P16234	PGFRA_HUMAN		Kd	9.29		CHEMBL
Serine/threonine-protein kinase RIO3	Kinase	O14730	RIOK3_HUMAN		Kd	6		CHEMBL
Hepatocyte growth factor receptor	Kinase	P08581	MET_HUMAN		Kd	6.09		CHEMBL
Receptor-interacting serine/threonine-protein kinase 2	Kinase	O43353	RIPK2_HUMAN		Kd	5		CHEMBL
Tyrosine-protein kinase JAK2	Kinase	O60674	JAK2_HUMAN		Kd	5.48		CHEMBL
Cyclin-G-associated kinase	Kinase	O14976	GAK_HUMAN		Kd	5.57		CHEMBL
Aurora kinase A	Kinase	O14965	AURKA_HUMAN		Kd	7.14		CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5	Kinase	Q13163	MP2K5_HUMAN		Kd	6.85		CHEMBL
Tyrosine-protein kinase ITK/TSK	Kinase	Q08881	ITK_HUMAN		Kd	5.92		CHEMBL
Mitogen-activated protein kinase kinase kinase MLT	Kinase	Q9NYL2	MLTK_HUMAN		Kd	5.59		CHEMBL
Interferon-induced, double-stranded RNA-activated protein kinase	Kinase	P19525	E2AK2_HUMAN		Kd	5.13		CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1	Kinase	Q92918	M4K1_HUMAN		Kd	6.48		CHEMBL
Tyrosine-protein kinase Fgr	Kinase	P09769	FGR_HUMAN		Kd	5.74		CHEMBL
Dual specificity protein kinase TTK	Kinase	P33981	TTK_HUMAN		Kd	5.41		CHEMBL
Serine/threonine-protein kinase 10	Kinase	O94804	STK10_HUMAN		Kd	5.92		CHEMBL
Serine/threonine-protein kinase 16	Kinase	O75716	STK16_HUMAN		Kd	6.43		CHEMBL
Serine/threonine-protein kinase PLK4	Kinase	O00444	PLK4_HUMAN		Ki	8.38		CHEMBL
AP2-associated protein kinase 1	Kinase	Q2M2I8	AAK1_HUMAN		Kd	5.92		CHEMBL
Tyrosine-protein kinase JAK3	Kinase	P52333	JAK3_HUMAN		Kd	5.51		CHEMBL
Casein kinase II subunit alpha'	Kinase	P19784	CSK22_HUMAN		Kd	5.55		CHEMBL
Tyrosine-protein kinase Yes	Kinase	P07947	YES_HUMAN		Kd	5.57		CHEMBL
Serine/threonine-protein kinase N2	Kinase	Q16513	PKN2_HUMAN		Kd	5.57		CHEMBL
Tyrosine-protein kinase CSK	Kinase	P41240	CSK_HUMAN		Kd	5.96		CHEMBL
Aurora kinase C	Kinase	Q9UQB9	AURKC_HUMAN		Kd	8.89		CHEMBL
High affinity nerve growth factor receptor	Kinase	P04629	NTRK1_HUMAN		Kd	5.74		CHEMBL
Platelet-derived growth factor receptor beta	Kinase	P09619	PGFRB_HUMAN		Kd	9.24		CHEMBL
Fibroblast growth factor receptor 1	Kinase	P11362	FGFR1_HUMAN		Kd	6.42		CHEMBL
Fibroblast growth factor receptor 2	Kinase	P21802	FGFR2_HUMAN		Kd	6.96		CHEMBL
Myosin-IIIa	Kinase	Q8NEV4	MYO3A_HUMAN		Kd	5.72		CHEMBL
Ankyrin repeat and protein kinase domain-containing protein 1	Kinase	Q8NFD2	ANKK1_HUMAN		Kd	5.44		CHEMBL
Mitogen-activated protein kinase kinase kinase 4	Kinase	Q9Y6R4	M3K4_HUMAN		Kd	5.25		CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 5	Kinase	Q9Y4K4	M4K5_HUMAN		Kd	6.26		CHEMBL
Misshapen-like kinase 1	Kinase	Q8N4C8	MINK1_HUMAN		Kd	6.25		CHEMBL
Leucine-rich repeat serine/threonine-protein kinase 2	Kinase	Q5S007	LRRK2_HUMAN		Kd	6.04		CHEMBL
Mast/stem cell growth factor receptor Kit	Kinase	P10721	KIT_HUMAN		Kd	9.31		CHEMBL
BMP-2-inducible protein kinase	Kinase	Q9NSY1	BMP2K_HUMAN		Kd	6		CHEMBL
TRAF2 and NCK-interacting protein kinase	Kinase	Q9UKE5	TNIK_HUMAN		Kd	6.74		CHEMBL
Calcium/calmodulin-dependent protein kinase kinase 2	Kinase	Q96RR4	KKCC2_HUMAN		Kd	5.82		CHEMBL
Aurora kinase B	Kinase	Q96GD4	AURKB_HUMAN		Kd	7.96		CHEMBL
STE20-like serine/threonine-protein kinase	Kinase	Q9H2G2	SLK_HUMAN		Kd	6		CHEMBL
Bone morphogenetic protein receptor type-1B	Kinase	O00238	BMR1B_HUMAN		Kd	5.54		CHEMBL
Non-receptor tyrosine-protein kinase TYK2	Kinase	P29597	TYK2_HUMAN		Kd	5.44		CHEMBL
Interleukin-1 receptor-associated kinase 1	Kinase	P51617	IRAK1_HUMAN		Kd	5.51		CHEMBL
Serine/threonine-protein kinase 4	Kinase	Q13043	STK4_HUMAN		Kd	5.85		CHEMBL
Calcium/calmodulin-dependent protein kinase kinase 1	Kinase	Q8N5S9	KKCC1_HUMAN		Kd	5.85		CHEMBL
Serine/threonine-protein kinase 3	Kinase	Q13188	STK3_HUMAN		Kd	5.66		CHEMBL
Serine/threonine-protein kinase ULK2	Kinase	Q8IYT8	ULK2_HUMAN		Kd	5		CHEMBL
Activated CDC42 kinase 1	Kinase	Q07912	ACK1_HUMAN		Kd	5.22		CHEMBL
Cyclin-dependent kinase 16	Kinase	Q00536	CDK16_HUMAN		Kd	5.28		CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 3	Kinase	Q8IVH8	M4K3_HUMAN		Kd	5.92		CHEMBL
Dual specificity testis-specific protein kinase 1	Kinase	Q15569	TESK1_HUMAN		Kd	5.37		CHEMBL
Serine/threonine-protein kinase MRCK beta	Kinase	Q9Y5S2	MRCKB_HUMAN		Kd	5.32		CHEMBL
G protein-coupled receptor kinase 4	Kinase	P32298	GRK4_HUMAN		Kd	5.64		CHEMBL
Serine/threonine-protein kinase ULK3	Kinase	Q6PHR2	ULK3_HUMAN		Kd	6.17		CHEMBL
Abelson tyrosine-protein kinase 2	Kinase	P42684	ABL2_HUMAN		Kd	7.15		CHEMBL
Activin receptor type-2B	Kinase	Q13705	AVR2B_HUMAN		Kd	5.28		CHEMBL
Tyrosine-protein kinase Blk	Kinase	P51451	BLK_HUMAN		Kd	5.51		CHEMBL
Angiopoietin-1 receptor	Kinase	Q02763	TIE2_HUMAN		Kd	6.51		CHEMBL
Proto-oncogene tyrosine-protein kinase ROS	Kinase	P08922	ROS1_HUMAN		Kd	5.49		CHEMBL
Ephrin type-B receptor 6	Kinase	O15197	EPHB6_HUMAN		Kd	6.44		CHEMBL
Mitogen-activated protein kinase 8	Kinase	P45983	MK08_HUMAN		Kd	5.41		CHEMBL
Macrophage colony-stimulating factor 1 receptor	Kinase	P07333	CSF1R_HUMAN		Kd	7.68		CHEMBL
Hormonally up-regulated neu tumor-associated kinase	Kinase	P57058	HUNK_HUMAN		Kd	5.82		CHEMBL
Discoidin domain-containing receptor 2	Kinase	Q16832	DDR2_HUMAN		Kd	5.28		CHEMBL
Tyrosine-protein kinase receptor Tie-1	Kinase	P35590	TIE1_HUMAN		Kd	7.01		CHEMBL
Serine/threonine-protein kinase PAK 4	Kinase	O96013	PAK4_HUMAN		Kd	5.35		CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret	Kinase	P07949	RET_HUMAN		Kd	7		CHEMBL
Epithelial discoidin domain-containing receptor 1	Kinase	Q08345	DDR1_HUMAN		Kd	6.47		CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 4	Kinase	O95819	M4K4_HUMAN		Kd	6.46		CHEMBL
Tyrosine-protein kinase Lck	Kinase	P06239	LCK_HUMAN		Kd	5.57		CHEMBL
Myosin light chain kinase 2, skeletal/cardiac muscle	Kinase	Q9H1R3	MYLK2_HUMAN		Kd	5.89		CHEMBL
Mitogen-activated protein kinase kinase kinase 9	Kinase	P80192	M3K9_HUMAN		Kd	5.52		CHEMBL
Mitogen-activated protein kinase kinase kinase 19	Kinase	Q56UN5	M3K19_HUMAN		Kd	6.57		CHEMBL
Tyrosine-protein kinase receptor UFO	Kinase	P30530	UFO_HUMAN		Kd	6.38		CHEMBL
NUAK family SNF1-like kinase 2	Kinase	Q9H093	NUAK2_HUMAN		Kd	5.89		CHEMBL
Dual specificity mitogen-activated protein kinase kinase 2	Kinase	P36507	MP2K2_HUMAN		Kd	5.59		CHEMBL
SRSF protein kinase 3	Kinase	Q9UPE1	SRPK3_HUMAN		Kd	5.64		CHEMBL
Tyrosine-protein kinase TXK	Kinase	P42681	TXK_HUMAN		Kd	5.62		CHEMBL
Mitogen-activated protein kinase kinase kinase 12	Kinase	Q12852	M3K12_HUMAN		Kd	5.77		CHEMBL
Myosin light chain kinase 3	Kinase	Q32MK0	MYLK3_HUMAN		Kd	5.77		CHEMBL
Receptor-interacting serine/threonine-protein kinase 1	Kinase	Q13546	RIPK1_HUMAN		Kd	5.60		CHEMBL
Mitogen-activated protein kinase kinase kinase 3	Kinase	Q99759	M3K3_HUMAN		Kd	5.55		CHEMBL
Serine/threonine-protein kinase RIO1	Kinase	Q9BRS2	RIOK1_HUMAN		Kd	5.92		CHEMBL
Receptor-interacting serine/threonine-protein kinase 4	Kinase	P57078	RIPK4_HUMAN		Kd	5.85		CHEMBL
Serine/threonine-protein kinase SIK1	Kinase	P57059	SIK1_HUMAN		Kd	5.68		CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2	Kinase	Q12851	M4K2_HUMAN		Kd	5.89		CHEMBL
Tyrosine-protein kinase Mer	Kinase	Q12866	MERTK_HUMAN		Kd	5.49		CHEMBL
Mitogen-activated protein kinase 10	Kinase	P53779	MK10_HUMAN		Kd	5.96		CHEMBL
Non-receptor tyrosine-protein kinase TNK1	Kinase	Q13470	TNK1_HUMAN		Kd	6.80		CHEMBL
Dual specificity mitogen-activated protein kinase kinase 1	Kinase	Q02750	MP2K1_HUMAN		Kd	5.57		CHEMBL
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN		Kd	8.82		CHEMBL

External reference:

ID	Source
C9LVQ0YUXG	UNII
4031332	VUID
N0000184323	NUI
D03218	KEGG_DRUG
4031332	VANDF
C1328149	UMLSCUI
CHEBI:66910	CHEBI
AXI	PDB_CHEM_ID
CHEMBL1289926	ChEMBL_ID
6450551	PUBCHEM_CID
DB06626	DRUGBANK_ID
D000077784	MESH_DESCRIPTOR_UI
8720	INN_ID
5659	IUPHAR_LIGAND_ID
1242999	RXNORM
187097	MMSL
28294	MMSL
d07823	MMSL
014143	NDDF
427882000	SNOMEDCT_US
429507005	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
INLYTA	HUMAN PRESCRIPTION DRUG LABEL	1	0069-0145	TABLET, FILM COATED	1 mg	ORAL	NDA	32 sections
INLYTA	HUMAN PRESCRIPTION DRUG LABEL	1	0069-0151	TABLET, FILM COATED	5 mg	ORAL	NDA	32 sections
INLYTA	HUMAN PRESCRIPTION DRUG LABEL	1	63539-026	TABLET, FILM COATED	1 mg	ORAL	NDA	29 sections
INLYTA	HUMAN PRESCRIPTION DRUG LABEL	1	63539-044	TABLET, FILM COATED	5 mg	ORAL	NDA	29 sections