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

Stem definition	Drug id	CAS RN
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors	4801	1195765-45-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: GSK2118436B dabrafenib mesylate tafinlar dabrafenib GSK2118436 dabrafenib mesilate	Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM, respectively, and other kinases such as SIK1, NEK11, and LIMK1 at higher concentrations. Some mutations in the BRAF gene, including those that result in BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Dabrafenib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo. Molecular weight: 519.56 Formula: C23H20F3N5O2S2 CLOGP: 4.61 LIPINSKI: 1 HAC: 7 HDO: 2 TPSA: 110.86 ALOGS: -5.20 ROTB: 5 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

GSK2118436B
dabrafenib mesylate
tafinlar
dabrafenib
GSK2118436
dabrafenib mesilate

Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM, respectively, and other kinases such as SIK1, NEK11, and LIMK1 at higher concentrations. Some mutations in the BRAF gene, including those that result in BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Dabrafenib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo.

Molecular weight: 519.56
Formula: C23H20F3N5O2S2
CLOGP: 4.61
LIPINSKI: 1
HAC: 7
HDO: 2
TPSA: 110.86
ALOGS: -5.20
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
Vd (Volume of distribution)	0.65 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2.86 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)	2.60 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Aug. 26, 2013	EMA	Novartis Europharm Limited
May 29, 2013	FDA	NOVARTIS PHARMS CORP

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
Pyrexia	2317.13	42.54	656	1948	53052	2302429
Malignant neoplasm progression	746.58	42.54	200	2404	11928	2343553
Chills	639.10	42.54	187	2417	15365	2340116
Death	378.28	42.54	201	2403	81267	2274214
Rash	336.46	42.54	168	2436	59390	2296091
Nausea	308.19	42.54	197	2407	111992	2243489
Vomiting	260.63	42.54	151	2453	71451	2284030
Metastatic malignant melanoma	247.74	42.54	43	2561	287	2355194
Fatigue	246.98	42.54	155	2449	84718	2270763
Panniculitis	239.62	42.54	45	2559	490	2354991
Diarrhoea	239.03	42.54	151	2453	83413	2272068
Metastases to central nervous system	217.52	42.54	53	2551	2095	2353386
Uveitis	211.45	42.54	49	2555	1556	2353925
Malignant melanoma	200.92	42.54	49	2555	1943	2353538
Dehydration	170.97	42.54	78	2526	22217	2333264
Visual impairment	156.72	42.54	61	2543	11694	2343787
Arthralgia	151.67	42.54	97	2507	54188	2301293
Ejection fraction decreased	142.37	42.54	40	2564	2761	2352720
Headache	128.32	42.54	102	2502	80077	2275404
Decreased appetite	126.15	42.54	69	2535	28822	2326659
General physical health deterioration	122.67	42.54	54	2550	14085	2341396
Neutropenia	115.36	42.54	59	2545	21489	2333992
Blood creatine phosphokinase increased	106.74	42.54	37	2567	5099	2350382
Malignant melanoma stage IV	104.19	42.54	15	2589	20	2355461
Myalgia	96.99	42.54	54	2550	23279	2332202
Vision blurred	95.76	42.54	46	2558	14622	2340859
C-reactive protein increased	92.32	42.54	35	2569	6220	2349261
Product use in unapproved indication	88.19	42.54	40	2564	11160	2344321
Hypotension	87.88	42.54	57	2547	32379	2323102
Dermatitis acneiform	87.12	42.54	21	2583	788	2354693
Aspartate aminotransferase increased	83.66	42.54	40	2564	12572	2342909
Alanine aminotransferase increased	82.56	42.54	41	2563	13991	2341490
Sepsis	80.11	42.54	44	2560	18444	2337037
Asthenia	77.52	42.54	61	2543	46865	2308616
Infection	72.88	42.54	41	2563	17988	2337493
Pulmonary embolism	72.77	42.54	41	2563	18042	2337439
Rash maculo-papular	70.79	42.54	26	2578	4226	2351255
Disease progression	69.43	42.54	39	2565	17056	2338425
Anaemia	67.92	42.54	50	2554	34742	2320739
Basal cell carcinoma	66.16	42.54	22	2582	2665	2352816
Rhabdomyolysis	65.89	42.54	28	2576	6676	2348805
Cough	65.56	42.54	48	2556	33069	2322412
Urinary tract infection	62.91	42.54	45	2559	29897	2325584
Erythema nodosum	62.22	42.54	16	2588	784	2354697
Confusional state	61.52	42.54	41	2563	24303	2331178
Peripheral swelling	57.82	42.54	35	2569	17562	2337919
Hyperkeratosis	57.12	42.54	15	2589	798	2354683
Chorioretinopathy	56.50	42.54	12	2592	251	2355230
Constipation	56.02	42.54	37	2567	21592	2333889
Hyponatraemia	55.71	42.54	31	2573	13294	2342187
Erythema	55.57	42.54	39	2565	25120	2330361
Product use issue	55.54	42.54	30	2574	12139	2343342
Abdominal pain	55.20	42.54	44	2560	34330	2321151
Pneumonia	54.60	42.54	51	2553	49245	2306236
Seizure	54.21	42.54	38	2566	24428	2331053
Malaise	53.08	42.54	53	2551	55532	2299949
Systemic inflammatory response syndrome	52.91	42.54	14	2590	767	2354714
Influenza like illness	52.88	42.54	29	2575	12085	2343396
Hepatic enzyme increased	52.79	42.54	27	2577	9775	2345706
Thrombocytopenia	52.64	42.54	34	2570	19097	2336384
Dizziness	52.49	42.54	54	2550	58611	2296870
Retinal detachment	51.86	42.54	15	2589	1144	2354337
Liver function test increased	51.74	42.54	19	2585	3082	2352399
Hyperpyrexia	51.56	42.54	13	2591	588	2354893
Metastasis	50.55	42.54	14	2590	912	2354569
Metastases to lung	50.01	42.54	16	2588	1715	2353766
Dry skin	46.82	42.54	22	2582	6630	2348851
Dysphagia	46.03	42.54	27	2577	12778	2342703
Hypokalaemia	45.11	42.54	25	2579	10629	2344852
Squamous cell carcinoma	45.00	42.54	14	2590	1369	2354112
Gamma-glutamyltransferase increased	44.16	42.54	20	2584	5542	2349939
Blood alkaline phosphatase increased	44.08	42.54	21	2583	6524	2348957
Oedema peripheral	43.73	42.54	33	2571	23730	2331751
Pneumonitis	43.45	42.54	18	2586	4021	2351460
Hepatocellular injury	43.38	42.54	18	2586	4037	2351444
Pain	43.21	42.54	50	2554	61807	2293674
Palmar-plantar erythrodysaesthesia syndrome	42.77	42.54	18	2586	4183	2351298

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
Pyrexia	2130.19	38.35	689	2268	45711	1698113
Malignant neoplasm progression	833.50	38.35	259	2698	13899	1729925
Chills	670.32	38.35	210	2747	11477	1732347
Death	481.23	38.35	299	2658	87144	1656680
Metastatic malignant melanoma	405.21	38.35	75	2882	366	1743458
Metastases to central nervous system	374.35	38.35	87	2870	1458	1742366
Ejection fraction decreased	278.88	38.35	74	2883	2171	1741653
Fatigue	259.46	38.35	167	2790	50614	1693210
Rash	247.53	38.35	147	2810	38546	1705278
Malignant melanoma	204.16	38.35	54	2903	1559	1742265
Nausea	195.79	38.35	141	2816	51055	1692769
Basal cell carcinoma	168.14	38.35	51	2906	2432	1741392
Vomiting	149.41	38.35	107	2850	38208	1705616
Decreased appetite	139.81	38.35	86	2871	23785	1720039
Dehydration	127.85	38.35	73	2884	17585	1726239
Visual impairment	122.37	38.35	51	2906	6167	1737657
General physical health deterioration	121.94	38.35	64	2893	13054	1730770
Uveitis	117.85	38.35	32	2925	1019	1742805
Diarrhoea	115.32	38.35	106	2851	53746	1690078
C-reactive protein increased	111.54	38.35	47	2910	5838	1737986
Disease progression	108.12	38.35	65	2892	17198	1726626
Blood creatine phosphokinase increased	108.11	38.35	52	2905	8804	1735020
Metastases to liver	101.48	38.35	34	2923	2233	1741591
Squamous cell carcinoma	95.54	38.35	31	2926	1840	1741984
Headache	94.20	38.35	78	2879	34298	1709526
Malignant melanoma stage IV	93.90	38.35	15	2942	22	1743802
Asthenia	93.62	38.35	78	2879	34592	1709232
Product use in unapproved indication	90.41	38.35	47	2910	9375	1734449
Arthralgia	85.41	38.35	63	2894	23381	1720443
Hyperkeratosis	74.01	38.35	20	2937	624	1743200
Second primary malignancy	72.67	38.35	22	2935	1037	1742787
Vision blurred	69.46	38.35	38	2919	8385	1735439
Hypotension	68.33	38.35	61	2896	29593	1714231
Confusional state	68.19	38.35	53	2904	21225	1722599
Neutropenia	66.27	38.35	49	2908	18211	1725613
Metastases to bone	65.79	38.35	23	2934	1715	1742109
Panniculitis	64.80	38.35	14	2943	163	1743661
Metastases to skin	64.69	38.35	13	2944	103	1743721
Metastases to meninges	63.04	38.35	15	2942	276	1743548
Atrial fibrillation	62.71	38.35	44	2913	15067	1728757
Thrombocytopenia	61.80	38.35	50	2907	21199	1722625
Chorioretinopathy	58.30	38.35	15	2942	385	1743439
Pain	57.76	38.35	53	2904	26604	1717220
Hepatic enzyme increased	57.71	38.35	31	2926	6590	1737234
Cough	53.33	38.35	44	2913	19153	1724671
Leukopenia	53.14	38.35	32	2925	8448	1735376
Squamous cell carcinoma of skin	53.07	38.35	18	2939	1224	1742600
Abdominal pain	51.01	38.35	45	2912	21445	1722379
Acute kidney injury	50.88	38.35	56	2901	34888	1708936
Blood lactate dehydrogenase increased	49.11	38.35	23	2934	3652	1740172
Malaise	47.63	38.35	50	2907	29515	1714309
Metastases to lymph nodes	46.85	38.35	15	2942	851	1742973
Influenza like illness	46.28	38.35	26	2931	6027	1737797
Aspartate aminotransferase increased	46.18	38.35	32	2925	10724	1733100
Anaemia	45.99	38.35	49	2908	29408	1714416
Rash maculo-papular	45.88	38.35	22	2935	3681	1740143
Metastases to lung	45.65	38.35	17	2940	1518	1742306
Hepatocellular injury	45.59	38.35	21	2936	3210	1740614
Hyponatraemia	43.94	38.35	29	2928	8971	1734853
Rhabdomyolysis	42.99	38.35	31	2926	11059	1732765
Pneumonia	42.89	38.35	59	2898	46123	1697701
Electrocardiogram QT prolonged	42.89	38.35	24	2933	5521	1738303
Night sweats	42.46	38.35	18	2939	2258	1741566
Alanine aminotransferase increased	42.37	38.35	32	2925	12246	1731578
Liver function test increased	41.98	38.35	16	2941	1523	1742301
Pneumonitis	41.76	38.35	21	2936	3894	1739930
Epilepsy	41.53	38.35	21	2936	3938	1739886
Concomitant disease aggravated	40.55	38.35	13	2944	740	1743084
Brain oedema	39.75	38.35	17	2940	2179	1741645
Body temperature increased	39.66	38.35	18	2939	2659	1741165
Blood alkaline phosphatase increased	38.86	38.35	22	2935	5173	1738651
Papilloedema	38.39	38.35	12	2945	629	1743195

Pharmacologic Action:

Source	Code	Description
ATC	L01XE23	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Protein kinase inhibitors
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D047428	Protein Kinase Inhibitors
CHEBI has role	CHEBI:35610	antineoplastic agent
FDA EPC	N0000175605	Kinase Inhibitor
FDA MoA	N0000185506	Cytochrome P450 3A4 Inducers
FDA MoA	N0000187064	Cytochrome P450 2B6 Inducers
FDA MoA	N0000187063	Cytochrome P450 2C8 Inducers
FDA MoA	N0000185507	Cytochrome P450 2C9 Inducers
FDA MoA	N0000185607	Cytochrome P450 2C19 Inducers
FDA MoA	N0000190107	Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA	N0000190108	Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA	N0000190110	Organic Anion Transporter 1 Inhibitors
FDA MoA	N0000190111	Organic Anion Transporter 3 Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Metastatic malignant melanoma	indication	443493003
Malignant Melanoma with BRAF V600E Mutation	indication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.56	acidic
pKa2	3.35	Basic
pKa3	0.43	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
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8835443	June 10, 2025	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8835443	June 10, 2025	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANAPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONAL TREATMENT OPTIONS
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8835443	June 10, 2025	TAFINLAR(R) IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST.
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8835443	June 10, 2025	TAFINLAR(R) IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8835443	June 10, 2025	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8835443	June 10, 2025	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANAPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONAL TREATMENT OPTIONS
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8835443	June 10, 2025	TAFINLAR(R) IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8835443	June 10, 2025	TAFINLAR(R) IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	IMPROVEMENT OF GLYCEMIC CONTROL IN TYPE 2 DIABETES PATIENTS BY ADMINISTERING A STARTING DOSE OF 10 MCG FOR 14 DAYS AND INCREASING TO A MAINTENANCE DOSE OF 20 MCG ON DAY 15
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	TAFINLAR IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATIONS AFTER CONFIRMING THE PRESENCE OF BRAF V600E MUTATION
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	IMPROVEMENT OF GLYCEMIC CONTROL IN TYPE 2 DIABETES PATIENTS BY ADMINISTERING A STARTING DOSE OF 10 MCG FOR 14 DAYS AND INCREASING TO A MAINTENANCE DOSE OF 20 MCG ON DAY 15
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	TAFINLAR IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	9233956	May 4, 2029	TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATIONS AFTER CONFIRMING THE PRESENCE OF BRAF V600E MUTATION
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	7994185	Jan. 20, 2030	TAFINLAR IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	7994185	Jan. 20, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	7994185	Jan. 20, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	7994185	Jan. 20, 2030	TREATMENT OF MELANOMA
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8415345	Jan. 20, 2030	TAFINLAR IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8415345	Jan. 20, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8415345	Jan. 20, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8415345	Jan. 20, 2030	TREATMENT OF MELANOMA
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	7994185	Jan. 20, 2030	TAFINLAR IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	7994185	Jan. 20, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	7994185	Jan. 20, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	7994185	Jan. 20, 2030	TREATMENT OF MELANOMA
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8415345	Jan. 20, 2030	TAFINLAR IS INDICATED AS A SINGLE AGENT FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8415345	Jan. 20, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8415345	Jan. 20, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8415345	Jan. 20, 2030	TREATMENT OF MELANOMA
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	IMPROVEMENT OF GLYCEMIC CONTROL IN TYPE 2 DIABETES PATIENTS BY ADMINISTERING A STARTING DOSE OF 10 MCG FOR 14 DAYS AND INCREASING TO A MAINTENANCE DOSE OF 20 MCG ON DAY 15
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	TAFINLAR IN COMBINATION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANAPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONAL TREATMENT OPTIONS
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8952018	Oct. 15, 2030	TAFINLAR(R) IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	IMPROVEMENT OF GLYCEMIC CONTROL IN TYPE 2 DIABETES PATIENTS BY ADMINISTERING A STARTING DOSE OF 10 MCG FOR 14 DAYS AND INCREASING TO A MAINTENANCE DOSE OF 20 MCG ON DAY 15
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	TAFINLAR IN COMBINATION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANAPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONAL TREATMENT OPTIONS
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8703781	Oct. 15, 2030	TAFINLAR IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	8952018	Oct. 15, 2030	TAFINLAR(R) IS INDICATED, IN COMBINATION WITH TRAMETINIB, FOR THE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST.

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	May 29, 2020	TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATION AS DETECTED BY AN FDA APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	May 29, 2020	TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E MUTATION AS DETECTED BY AN FDA APPROVED TEST.
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	June 22, 2020	MEKINIST, IN COMBINATION WITH DABRAFENIB, FOR THE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST.
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	June 22, 2020	MEKINIST, IN COMBINATION WITH DABRAFENIB, FOR THE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST.
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	Jan. 9, 2021	DABRAFENIB IN COMBO WITH TRAMETINIB FOR TX. OF PTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST. THIS INDICATION IS BASED ON THE DEMONSTRATION OF DURABLE RESPONSE RATE
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	Jan. 9, 2021	DABRAFENIB IN COMBO WITH TRAMETINIB FOR TX. OF PTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST. THIS INDICATION IS BASED ON THE DEMONSTRATION OF DURABLE RESPONSE RATE
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	April 30, 2021	DABRAFENIB IN COMBINATION WITH TRAMETINIB FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	April 30, 2021	DABRAFENIB IN COMBINATION WITH TRAMETINIB FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	May 4, 2021	DABRAFENIB IN COMBINATION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANAPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONAL TREATMENT OPTIONS
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	May 4, 2021	DABRAFENIB IN COMBINATION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANAPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONAL TREATMENT OPTIONS
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	Oct. 6, 2022	ADDITION OF STUDY BRF117277, A NON-RANDOMIZED, OPEN-LABEL, MULTI-CENTER, MULTI-COHORT TRIAL OF DABRAFENIB PLUS TRAMETINIB IN SUBJECTS WITH BRAF MUTATION-POSITIVE MELANOMA THAT HAS METASTASIZED TO THE BRAIN
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	Oct. 6, 2022	ADDITION OF STUDY BRF117277, A NON-RANDOMIZED, OPEN-LABEL, MULTI-CENTER, MULTI-COHORT TRIAL OF DABRAFENIB PLUS TRAMETINIB IN SUBJECTS WITH BRAF MUTATION-POSITIVE MELANOMA THAT HAS METASTASIZED TO THE BRAIN
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	June 22, 2024	DABRAFENIB IN COMBINATION WITH TRAMETINIB, FOR THE TX. OF PTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	June 22, 2024	DABRAFENIB IN COMBINATION WITH TRAMETINIB, FOR THE TX. OF PTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	April 30, 2025	TRAMETINIB IS INDICATED, IN COMBINATION WITH DABRAFENIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	April 30, 2025	TRAMETINIB IS INDICATED, IN COMBINATION WITH DABRAFENIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 50MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	May 4, 2025	TRAMETINIB AND DABRAFENIB IN COMBINATION, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANAPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONAL TREATMENT OPTIONS
EQ 75MG BASE	TAFINLAR	NOVARTIS	N202806	May 29, 2013	RX	CAPSULE	ORAL	May 4, 2025	TRAMETINIB AND DABRAFENIB IN COMBINATION, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANAPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONAL TREATMENT OPTIONS

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Serine/threonine-protein kinase B-raf	Kinase	P15056	BRAF_HUMAN	INHIBITOR	IC50	9.15	WOMBAT-PK	CHEMBL
TGF-beta receptor type-1	Kinase	P36897	TGFR1_HUMAN		IC50	5.43	CHEMBL
RAF proto-oncogene serine/threonine-protein kinase	Kinase	P04049	RAF1_HUMAN		IC50	6.82	CHEMBL
Serine/threonine-protein kinase A-Raf	Kinase	P10398	ARAF_HUMAN		IC50	7.59	CHEMBL

External reference:

ID	Source
D10064	KEGG_DRUG
C3644554	UMLSCUI
B6DC89I63E	UNII
1195768-06-9	SECONDARY_CAS_RN
9458	INN_ID
P06	PDB_CHEM_ID
DB08912	DRUGBANK_ID
CHEBI:75045	CHEBI
6494	IUPHAR_LIGAND_ID
C561627	MESH_SUPPLEMENTAL_RECORD_UI
CHEMBL2028663	ChEMBL_ID
CHEMBL2105729	ChEMBL_ID
44462760	PUBCHEM_CID
703646006	SNOMEDCT_US
1424911	RXNORM
29476	MMSL
d08103	MMSL
015042	NDDF
4032496	VANDF
703641001	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Tafinlar	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0681	CAPSULE	75 mg	ORAL	NDA	18 sections
Tafinlar	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0682	CAPSULE	50 mg	ORAL	NDA	18 sections