VEMURAFENIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H18ClF2N3O3S
Molecular Weight	489.922
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCS(=O)(=O)NC1=C(F)C(C(=O)C2=CNC3=NC=C(C=C23)C4=CC=C(Cl)C=C4)=C(F)C=C1

InChI

InChIKey=GPXBXXGIAQBQNI-UHFFFAOYSA-N

InChI=1S/C23H18ClF2N3O3S/c1-2-9-33(31,32)29-19-8-7-18(25)20(21(19)26)22(30)17-12-28-23-16(17)10-14(11-27-23)13-3-5-15(24)6-4-13/h3-8,10-12,29H,2,9H2,1H3,(H,27,28)

HIDE SMILES / InChI

Molecular Formula	C23H18ClF2N3O3S
Molecular Weight	489.922
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429s000lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.webmd.com/melanoma-skin-cancer/news/20110817/zelboraf-approved-for-late-stage-melanoma

Vemurafenib (trade name Zelboraf) is a low molecular weight, orally available kinase inhibitor. It inhibits of some mutated forms of BRAF serinethreonine kinase, including BRAF V600E and is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5 and FGR at similar concentrations. Vemurafenib is not recommended for use in patients with wild-type BRAF melanoma. Zelboraf does not cure melanoma, but stops it's progression. Some 26% of patients in clinical trials developed a non melanoma form of skin cancer called cutaneous squamous cell carcinoma, which can usually be removed via relatively simple surgery. Other side effects include joint pain, rash, hair loss, fatigue, nausea, and skin sensitivity to sunlight. Patients taking Zelboraf must avoid sun exposure. It's not yet clear how long Zelboraf can increase melanoma survival.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase B-raf 20 Target ID: CHEMBL5145 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429s000lbl.pdf	Inhibitor 8228		31.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced melanoma 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429s000lbl.pdf	Secondary		Approved 8360	ZELBORAF Approved Use Indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Limitation of Use: ZELBORAF is not indicated for treatment of patients with wild-type BRAF melanoma. Launch Date 1.31353923E12

C_max

Value	Dose	Analyte	Population
62 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429s000lbl.pdf	960 mg 2 times / day multiple, oral dose: 960 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
61.4 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24178368	960 mg 2 times / day multiple, oral dose: 960 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
17.2 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24178368	240 mg 2 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
601 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429s000lbl.pdf	960 mg 2 times / day multiple, oral dose: 960 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3530.3 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24178368	960 mg 2 times / day multiple, oral dose: 960 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
920.3 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24178368	240 mg 2 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
34.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24178368	960 mg 2 times / day multiple, oral dose: 960 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
31.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24178368	240 mg 2 times / day multiple, oral dose: 240 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429s000lbl.pdf	960 mg 2 times / day multiple, oral dose: 960 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VEMURAFENIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
960 mg 2 times / day multiple, oral Recommended\|MTD Dose: 960 mg, 2 times / day Route: oral Route: multiple Dose: 960 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429Orig1s000SumR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf	unhealthy, median age was 54 years n = 336 Health Status: unhealthy Condition: melanoma Age Group: median age was 54 years Sex: M+F Population Size: 336 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429Orig1s000SumR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf	Other AEs: Rash, Photosensitivity reaction... Other AEs: Rash (grade 3, 8%) Photosensitivity reaction (grade 3, 3%) Alopecia (grade 3, <1%) Pruritus (grade 3, 1%) Hyperkeratosis (grade 3, 1%) Rash maculo-papular (grade 3, 2%) Rash papular (grade 3, <1%) Arthralgia (grade 3, 4%) Myalgia (grade 3, <1%) Pain in extremity (grade 3, <1%) Back pain (grade 3, <1%) Fatigue (grade 3, 2%) Edema peripheral (grade 3, <1%) Pyrexia (grade 3, <1%) Asthenia (grade 3, <1%) Nausea (grade 3, 2%) Diarrhea (grade 3, <1%) Vomiting (grade 3, 1%) Constipation (grade 3, <1%) Headache (grade 3, <1%) Skin papilloma (grade 3, <1%) Squamous cell carcinoma of skin (grade 3, 22%) Seborrheic keratosis (grade 3, <1%) GGT increased (grade 3, 3%) Rash (37%) Photosensitivity reaction (33%) Alopecia (45%) Pruritus (23%) Hyperkeratosis (24%) Rash maculo-papular (9%) Actinic keratosis (8%) Dry skin (19%) Rash papular (5%) Erythema (14%) Arthralgia (53%) Myalgia (13%) Pain in extremity (18%) Musculoskeletal pain (8%) Back pain (8%) Fatigue (38%) Edema peripheral (17%) Pyrexia (19%) Asthenia (11%) Nausea (35%) Diarrhea (28%) Vomiting (18%) Constipation (12%) Headache (23%) Dysgeusia (14%) Skin papilloma (21%) Squamous cell carcinoma of skin (24%) Seborrheic keratosis (10%) GGT increased (5%) Decreased appetite (18%) Cough (8%) Sunburn (10%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202429Orig1s000SumR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf
960 mg 2 times / day multiple, oral Recommended\|MTD Dose: 960 mg, 2 times / day Route: oral Route: multiple Dose: 960 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.75	unhealthy, median age was 54 years n = 336 Health Status: unhealthy Condition: melanoma Age Group: median age was 54 years Sex: M+F Population Size: 336 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.75	Disc. AE: Arthralgia, Dysphagia... AEs leading to discontinuation/dose reduction: Arthralgia (2%) Dysphagia (2%) Pneumonia (2%) Brain metastases (1%) Dyspnea (1%) Pneumonia (1%) Thrombocytopenia (1%) Abdominal pain (1%) Aortic aneurysm rupture (1%) Ascites (1%) Atrial fibrillation (1%) Blood alkaline phosphatase increased (1%) Blood bilirubin increased (1%) Chest pain (1%) Choking (1%) Cognitive disorder (1%) Hyperemia of conjunctiva (1%) Dehydration (1%) Diplopia (1%) Dyspepsia (1%) Esophageal pain (1%) Fatigue (1%) Gait disturbance (1%) GGT increased (1%) Gastroesophageal reflux (1%) Hepatitis acute (1%) Hyponatremia (1%) Intracranial tumor hemorrhage (1%) Myocardial infarction (1%) Pain (1%) Pancreatitis (1%) Rash (1%) Renal impairment (1%) Stevens-Johnson syndrome (1%) Thrombocytopenia (1%) Toxic skin eruption (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.75
960 mg 2 times / day multiple, oral Recommended\|MTD Dose: 960 mg, 2 times / day Route: oral Route: multiple Dose: 960 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.80	unhealthy, median age was 54 years n = 336 Health Status: unhealthy Condition: melanoma Age Group: median age was 54 years Sex: M+F Population Size: 336 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.80	Other AEs: LDH increased, Alkaline phosphatase increased... Other AEs: LDH increased (grade 3, 2.7%) Alkaline phosphatase increased (grade 3, 3%) ALT increased (grade 3, 2.7%) GGT increased (grade 3, 11.3%) AST increased (grade 3, <1%) Bilirubin increased (grade 3, 1.8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.80
960 mg 2 times / day multiple, oral Recommended\|MTD Dose: 960 mg, 2 times / day Route: oral Route: multiple Dose: 960 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.82	unhealthy, median age was 54 years n = 336 Health Status: unhealthy Condition: melanoma Age Group: median age was 54 years Sex: M+F Population Size: 336 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.82	Other AEs: Arthritis, Joint effusion... Other AEs: Arthritis (grade 3, <1%) Joint effusion (grade 3, <1%) Atrial fibrillation (grade 3, <1%) Myocardial infarction (grade 3, <1%) Pericarditis (grade 3, <1%) QT interval prolonged (grade 3, 2.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.82
960 mg 2 times / day multiple, oral Recommended\|MTD Dose: 960 mg, 2 times / day Route: oral Route: multiple Dose: 960 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.86	unhealthy, median age was 54 years n = 336 Health Status: unhealthy Condition: melanoma Age Group: median age was 54 years Sex: M+F Population Size: 336 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.86	Other AEs: Rash, Keratoacanthoma... Other AEs: Rash (grade 3, 8.3%) Keratoacanthoma (grade 3, 8.6%) Arthralgia (grade 3, 4.5%) GGT increased (grade 3, 3.3%) Photosensitivity reaction (grade 3, 2.7%) Maculopapular rash (grade 3, 2.4%) Blood alkaline phosphatase increased (grade 3, 2.7%) Fatigue (grade 3, 2.1%) Dyspnea (grade 3, 2.1%) Nausea (grade 3, 2.1%) ALT increased (grade 3, 1.8%) Pain in extremity (grade 3, 1.5%) Pruritus (grade 3, 1.5%) Vomiting (grade 3, 1.2%) Pain (grade 3, 1.2%) Blood bilirubin increased (grade 3, 1.2%) Hyperkeratosis (grade 3, 1.2%) Anemia (grade 3, <1%) Thrombocytopenia (grade 3, <1%) Neutropenia (grade 3, <1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.86
960 mg 2 times / day multiple, oral Recommended\|MTD Dose: 960 mg, 2 times / day Route: oral Route: multiple Dose: 960 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.87	unhealthy, median age was 54 years n = 336 Health Status: unhealthy Condition: melanoma Age Group: median age was 54 years Sex: M+F Population Size: 336 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.87	Other AEs: Hyperglycemia, Creatinine increased... Other AEs: Hyperglycemia (grade 3, 2.1%) Creatinine increased (grade 3, 1.5%) Hyperkalemia (grade 3, 1.2%) Hypercalcemia (grade 3, 2%) Decreased hemoglobin (grade 3, 3.7%) Lymphocyte count decreased (grade 3, 8.3%) Hypoalbuminemia (grade 3, 1.3%) Hypophosphatemia (grade 3, 3.5%) Neutrophil count decreased (grade 3, <1%) WBC decreased (grade 3, <1%) Platelets decreased (grade 3, <1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000MedR.pdf Page: 202429Orig1s000MedR.pdf - p.87
960 mg 2 times / day multiple, oral Recommended\|MTD Dose: 960 mg, 2 times / day Route: oral Route: multiple Dose: 960 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/	unhealthy, median age was 63 years n = 32 Health Status: unhealthy Condition: metastatic melanoma Age Group: median age was 63 years Sex: M+F Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/	Other AEs: Arthralgia, Rash... Other AEs: Arthralgia (grade 3, 3%) Rash (grade 3, 3%) Squamous cell carcinoma, keratoacanthoma-type (grade 3, 31%) Nausea (grade 3, 3%) Fatigue (grade 3, 6%) Photosensitivity reaction (grade 3, 3%) Palmar-plantar erythrodysesthesia syndrome (grade 3, 6%) Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/
1120 mg 2 times / day multiple, oral Dose: 1120 mg, 2 times / day Route: oral Route: multiple Dose: 1120 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/	unhealthy, median age was 63 years n = 6 Health Status: unhealthy Condition: metastatic melanoma Age Group: median age was 63 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/	DLT: Arthralgia, Rash... Other AEs: Squamous cell carcinoma, keratoacanthoma-type, Fatigue... Dose limiting toxicities: Arthralgia (grade 3, 17%) Rash (grade 3, 50%) Other AEs: Squamous cell carcinoma, keratoacanthoma-type (grade 3, 33%) Fatigue (grade 3, 33%) Pruritus (grade 3, 17%) Lymphopenia (grade 3, 17%) Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/
240 mg 2 times / day multiple, oral Dose: 240 mg, 2 times / day Route: oral Route: multiple Dose: 240 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/	unhealthy, median age was 63 years n = 4 Health Status: unhealthy Condition: metastatic melanoma Age Group: median age was 63 years Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/	Other AEs: Squamous cell carcinoma, keratoacanthoma-type... Other AEs: Squamous cell carcinoma, keratoacanthoma-type (grade 3, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/
360 mg 2 times / day multiple, oral Dose: 360 mg, 2 times / day Route: oral Route: multiple Dose: 360 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/	unhealthy, median age was 63 years n = 8 Health Status: unhealthy Condition: metastatic melanoma Age Group: median age was 63 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/	Other AEs: Squamous cell carcinoma, keratoacanthoma-type... Other AEs: Squamous cell carcinoma, keratoacanthoma-type (grade 3, 38%) Sources: https://pubmed.ncbi.nlm.nih.gov/20818844/
1600 mg 2 times / day multiple, oral Highest studied dose Dose: 1600 mg, 2 times / day Route: oral Route: multiple Dose: 1600 mg, 2 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000	unhealthy n = 3 Health Status: unhealthy Condition: cancer Population Size: 3 Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000	Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000
1120 mg 2 times / day multiple, oral Dose: 1120 mg, 2 times / day Route: oral Route: multiple Dose: 1120 mg, 2 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000	unhealthy n = 5 Health Status: unhealthy Condition: cancer Population Size: 5 Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000	DLT: Rash, Fatigue... Dose limiting toxicities: Rash (60%) Fatigue (60%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000
360 mg 2 times / day multiple, oral Dose: 360 mg, 2 times / day Route: oral Route: multiple Dose: 360 mg, 2 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000	unhealthy Health Status: unhealthy Condition: cancer Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000	Other AEs: ALT increased... Other AEs: ALT increased (grade 3) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000
720 mg 2 times / day multiple, oral Dose: 720 mg, 2 times / day Route: oral Route: multiple Dose: 720 mg, 2 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000	unhealthy n = 6 Health Status: unhealthy Condition: cancer Population Size: 6 Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000	DLT: Pancytopenia... Dose limiting toxicities: Pancytopenia (grade 4) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2009.27.15_suppl.9000

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 768 substrate 1709	inhibitor 1752	inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2C19 1463 P-gp 1437 OATP1B1 781 OATP1B3 700	P-gp 1527 OATP1B1 403 OATP1B3 347	P-gp 257 CYP1A2 689 CYP2B6 538

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=16 Page: -	mild [IC50 33.2 uM]	yes (co-administration study) Comment: Vemurafenib increased the AUC0-last of the CYP2D6 substrate (dextromethorphan) by 47%, and therefore can be classified as a weak inhibitor of CYP2D6 based on the FDA guidance. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=16 Page: -
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=16 Page: -	moderate [IC50 32.5 uM]	yes (co-administration study) Comment: Сoadministration of vemurafenib increased the AUC0-last of caffeine (CYP1A2 substrate) by 2.6-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=16 Page: -
OATP1B1 796	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=45 Page: -	no
OATP1B3 709	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=45 Page: -	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=41 Page: -	yes [IC50 22.5 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=41 Page: -	yes [IC50 5.9 uM]
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=72 Page: -	yes
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=72 Page: -	yes
P-gp 1626	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=72 Page: -	yes
P-gp 1626	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=18 Page: -	yes
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=16 Page: -	yes	yes (co-administration study) Comment: Сoadministration of vemurafenib decreased the AUC0-last of midazolam (CYP3A4 substrate) by 39%, Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=16 Page: -

Drug as victim

Target	Modality	Activity
OATP1B1 403	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=45 Page: -	no
OATP1B3 347	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=45 Page: -	no
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=16 Page: -	yes
P-gp 1527	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000ClinPharmR.pdf#page=18 Page: -	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202429Orig1s000PharmR.pdf#page=51 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63637	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63637
ChemicalBook	CB02550000	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02550000
ChemicalBook	CB22515128	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB22515128
MolPort	MolPort-009-200-481	https://www.molport.com/shop/molecule-link/MolPort-009-200-481
Selleck Chemicals	PLX-4032	http://www.selleckchem.com/products/PLX-4032.html
ZINC	ZINC000052509366	http://zinc15.docking.org/substances/ZINC000052509366
eMolecules	32176418	https://www.emolecules.com/cgi-bin/more?vid=32176418

PubMed

Title	Date	PubMed
		252160309
The BRAFT1799A mutation confers sensitivity of thyroid cancer cells to the BRAFV600E inhibitor PLX4032 (RG7204).	2011 Jan 28	21185263
Novel immunotherapeutic agents and small molecule antagonists of signalling kinases for the treatment of metastatic melanoma.	2011 Jul 9	21770473
Overcoming metastatic melanoma with BRAF inhibitors.	2011 May	21656352
BRAF targeted therapy changes the treatment paradigm in melanoma.	2011 May 24	21606968
New drugs in melanoma: it's a whole new world.	2011 Sep	21802280
Conformation-specific effects of Raf kinase inhibitors.	2012 Sep 13	22808911
A multisite blinded study for the detection of BRAF mutations in formalin-fixed, paraffin-embedded malignant melanoma.	2013	23584600
Characterization of vemurafenib phototoxicity in a mouse model.	2014 Jan	24154489
Copper is required for oncogenic BRAF signalling and tumorigenesis.	2014 May 22	24717435
The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells.	2015 Jan 16	25477506
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541
Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers.	2015 Sep 14	26343583

Patents

Sample Use Guides

In Vivo Use Guide

960 mg twice daily. Administer ZELBORAF approximately 12 hours apart with or without a meal. Management of symptomatic adverse drug reactions may require dose reduction, treatment interruption, or treatment discontinuation of ZELBORAF. Dose reductions resulting in a dose below 480 mg twice daily are not recommended

Route of Administration: Oral

In Vitro Use Guide

The antitumor effects of vemurafenib against SM1 cells were tested by in vitro MTS cell proliferation assay after 72 hours of treatment. The IC50 of vemurafenib was 14 uM, which is approximately one log higher than the sensitivity of M229 (IC50 of 0.5 uM), a BRAF V600E mutant human melanoma cell line highly sensitive to vemurafenib, and at a similar range as the relatively resistant BRAF V600E mutant human melanoma cell line M233 (IC50 of 15 uM).

Substance Class	Chemical Created by `admin` on `Thu Jul 06 01:45:01 UTC 2023` Edited by `admin` on `Thu Jul 06 01:45:01 UTC 2023`
Record UNII	207SMY3FQT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VEMURAFENIB

Official Name

English

RG 7204

Code

English

VEMURAFENIB [ORANGE BOOK]

Common Name

English

ZELBORAF

Brand Name

English

N-(3-((5-(4-CHLOROPHENYL)-1H-PYRROLO(2,3-B)PYRIDIN-3-YL)CARBONYL)-2,4- DIFLUOROPHENYL)PROPANE-1-SULFONAMIDE

Systematic Name

English

VEMURAFENIB [VANDF]

Common Name

English

RO-51-85426

Code

English

VEMURAFENIB [MART.]

Common Name

English

VEMURAFENIB [USAN]

Common Name

English

PLX-4032

Code

English

RO 5185426

Code

English

RO-5185426

Code

English

VEMURAFENIB [JAN]

Common Name

English

Vemurafenib [WHO-DD]

Common Name

English

vemurafenib [INN]

Common Name

English

1-PROPANESULFONAMIDE, N-(3-((5-(4-CHLOROPHENYL)-1H-PYRROLO(2,3-B)PYRIDIN-3- YL)CARBONYL)-2,4-DIFLUOROPHENYL)-

Systematic Name

English

VEMURAFENIB [MI]

Common Name

English

PLX4032

Code

English

RG-7204

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

325310