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	613.53	41.07	155	1020	16940	2339970
Diarrhoea	481.33	41.07	186	989	83378	2273532
Renal cancer	342.05	41.07	56	1119	628	2356282
Death	265.57	41.07	122	1053	81346	2275564
Hypertension	239.99	41.07	84	1091	27277	2329633
Neoplasm progression	229.56	41.07	55	1120	4613	2352297
Metastatic renal cell carcinoma	223.13	41.07	34	1141	227	2356683
Decreased appetite	209.12	41.07	77	1098	28814	2328096
Fatigue	199.80	41.07	102	1073	84771	2272139
Renal cell carcinoma	174.00	41.07	32	1143	725	2356185
Dysphonia	132.71	41.07	38	1137	6326	2350584
Weight decreased	125.13	41.07	53	1122	28318	2328592
Dehydration	116.34	41.07	47	1128	22248	2334662
Nausea	114.78	41.07	79	1096	112110	2244800
Palmar-plantar erythrodysaesthesia syndrome	114.67	41.07	31	1144	4170	2352740
Hypothyroidism	108.22	41.07	30	1145	4427	2352483
Stomatitis	100.80	41.07	34	1141	9676	2347234
Blood pressure increased	99.64	41.07	39	1136	16947	2339963
Asthenia	94.03	41.07	51	1124	46875	2310035
Vomiting	69.39	41.07	49	1126	71553	2285357
Proteinuria	59.20	41.07	17	1158	2833	2354077
Posterior reversible encephalopathy syndrome	56.95	41.07	16	1159	2464	2354446
Constipation	53.06	41.07	27	1148	21602	2335308
Renal cancer metastatic	47.75	41.07	8	1167	102	2356808
General physical health deterioration	44.69	41.07	21	1154	14118	2342792

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	1855.50	44.22	499	2446	16764	1727072
Diarrhoea	942.96	44.22	399	2546	53453	1690383
Renal cancer	856.43	44.22	162	2783	929	1742907
Death	680.34	44.22	372	2573	87071	1656765
Dysphonia	650.36	44.22	159	2786	3396	1740440
Hypertension	558.89	44.22	208	2737	19240	1724596
Metastatic renal cell carcinoma	524.54	44.22	98	2847	513	1743323
Fatigue	501.46	44.22	255	2690	50526	1693310
Renal cell carcinoma	491.40	44.22	108	2837	1400	1742436
Neoplasm progression	451.89	44.22	117	2828	3150	1740686
Decreased appetite	385.44	44.22	169	2776	23702	1720134
Blood pressure increased	235.83	44.22	95	2850	10658	1733178
Nausea	212.70	44.22	148	2797	51048	1692788
Weight decreased	206.98	44.22	109	2836	22644	1721192
Palmar-plantar erythrodysaesthesia syndrome	199.77	44.22	63	2882	3444	1740392
Neoplasm malignant	178.71	44.22	61	2884	4278	1739558
Stomatitis	176.80	44.22	64	2881	5340	1738496
Asthenia	174.17	44.22	113	2832	34557	1709279
Hypothyroidism	149.92	44.22	47	2898	2513	1741323
Constipation	145.06	44.22	75	2870	14925	1728911
Dehydration	133.56	44.22	75	2870	17583	1726253
Proteinuria	117.07	44.22	40	2905	2804	1741032
Malaise	102.66	44.22	77	2868	29488	1714348
Pain in extremity	99.27	44.22	63	2882	18409	1725427
Headache	96.59	44.22	79	2866	34297	1709539
Renal impairment	94.86	44.22	53	2892	12261	1731575
Dyspnoea	93.67	44.22	93	2852	51966	1691870
Vomiting	87.12	44.22	78	2867	38237	1705599
Oral pain	86.78	44.22	27	2918	1403	1742433
Renal cancer metastatic	85.19	44.22	18	2927	188	1743648
Second primary malignancy	72.76	44.22	22	2923	1037	1742799
Acute kidney injury	63.71	44.22	63	2882	34881	1708955
Aphonia	63.48	44.22	17	2928	514	1743322
Dysgeusia	62.72	44.22	30	2915	5019	1738817
Arthralgia	59.72	44.22	51	2894	23393	1720443
Blood thyroid stimulating hormone increased	55.85	44.22	16	2929	623	1743213
Nephrotic syndrome	54.67	44.22	19	2926	1397	1742439
Blood creatinine increased	54.28	44.22	39	2906	13907	1729929
Glossodynia	54.08	44.22	16	2929	699	1743137
Posterior reversible encephalopathy syndrome	53.91	44.22	19	2926	1456	1742380
Pneumothorax	52.54	44.22	22	2923	2690	1741146
General physical health deterioration	49.48	44.22	36	2909	13082	1730754
Dry mouth	47.83	44.22	23	2922	3890	1739946
Cough	47.30	44.22	41	2904	19156	1724680
Blister	46.85	44.22	23	2922	4069	1739767
Dry skin	45.92	44.22	22	2923	3690	1740146
Malignant urinary tract neoplasm	45.76	44.22	8	2937	26	1743810

Pharmacologic Action:

Source	Code	Description
ATC	L01XE17	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Protein kinase inhibitors
CHEBI has role	CHEBI:35610	antineoplastic agent
FDA EPC	N0000175605	Kinase Inhibitor
FDA MoA	N0000020000	Receptor Tyrosine Kinase Inhibitors
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D047428	Protein Kinase 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)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
1MG	INLYTA	PF PRISM CV	N202324	Jan. 27, 2012	RX	TABLET	ORAL	7141581	June 30, 2020	TREATMENT OF RENAL CELL CARCINOMA
5MG	INLYTA	PF PRISM CV	N202324	Jan. 27, 2012	RX	TABLET	ORAL	7141581	June 30, 2020	TREATMENT OF RENAL CELL CARCINOMA

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
D000077784	MESH_DESCRIPTOR_UI
4031332	VUID
N0000184323	NUI
C1700874	UMLSCUI
D03218	KEGG_DRUG
429507005	SNOMEDCT_US
427882000	SNOMEDCT_US
1242999	RXNORM
014143	NDDF
28294	MMSL
d07823	MMSL
4031332	VANDF
C9LVQ0YUXG	UNII
8720	INN_ID
6450551	PUBCHEM_CID
CHEBI:66910	CHEBI
AXI	PDB_CHEM_ID
DB06626	DRUGBANK_ID
5659	IUPHAR_LIGAND_ID
CHEMBL1289926	ChEMBL_ID

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	19 sections
INLYTA	HUMAN PRESCRIPTION DRUG LABEL	1	0069-0151	TABLET, FILM COATED	5 mg	ORAL	NDA	19 sections
INLYTA	HUMAN PRESCRIPTION DRUG LABEL	1	63539-026	TABLET, FILM COATED	1 mg	ORAL	NDA	19 sections
INLYTA	HUMAN PRESCRIPTION DRUG LABEL	1	63539-044	TABLET, FILM COATED	5 mg	ORAL	NDA	19 sections