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Details

Stereochemistry ACHIRAL
Molecular Formula C21H15ClF4N4O3.H2O
Molecular Weight 500.8314
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of REGORAFENIB MONOHYDRATE

SMILES

CNC(=O)c1cc(ccn1)Oc2ccc(c(c2)F)NC(=Nc3ccc(c(c3)C(F)(F)F)Cl)O.O

InChI

InChIKey=ZOPOQLDXFHBOIH-UHFFFAOYSA-N
InChI=1S/C21H15ClF4N4O3.H2O/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26;/h2-10H,1H3,(H,27,31)(H2,29,30,32);1H2

HIDE SMILES / InChI

Molecular Formula C21H15ClF4N4O3
Molecular Weight 482.8161
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: http://www.news-medical.net/news/20140220/Bayer-enrolls-patients-for-Phase-III-trial-of-Stivarga-(regorafenib)-tablets-in-colorectal-cancer.aspx; http://www.ncbi.nlm.nih.gov/pubmed/?term=21170960

Regorafenib (trade name Stivarga) is an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model, and inhibition of tumor growth as well as anti-metastatic activity in several mouse xenograft models including some for human colorectal carcinoma. Since 2009 it was studied as a potential treatment option in multiple tumor types. Stivarga is approved by FDA to treat two different tumor types: metastatic colorectal cancer in patients who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy (approved in 2012) and to treat patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor who have been previously treated with imatinib mesylate and sunitinib malate (approved in 2013).

CNS Activity

Curator's Comment:: In a single dose distribution study in pregnant rats, there was increased penetration of regorafenib across the blood-brain barrier in fetuses compared to dams.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P04049
Gene ID: 5894
Gene Symbol: RAF1
Target Organism: Homo sapiens (Human)
2.5 nM [IC50]
Target ID: P07949
Gene ID: 5979
Gene Symbol: RET
Target Organism: Homo sapiens (Human)
1.5 nM [IC50]
Target ID: P35968
Gene ID: 3791
Gene Symbol: KDR
Target Organism: Homo sapiens (Human)
4.20000000000000018 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
STIVARGA

Approved Use

Indicated for the treatment of patients with: metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy; locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Launch Date

1348704000000
Secondary
STIVARGA

Approved Use

Indicated for the treatment of patients with: metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy; locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

Launch Date

1348704000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2522.2 μg/L
160 mg 1 times / day steady-state, oral
dose: 160 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
REGORAFENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
33042.8 μg × h/mL
160 mg 1 times / day steady-state, oral
dose: 160 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
REGORAFENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
30.4 h
160 mg 1 times / day steady-state, oral
dose: 160 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
REGORAFENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.5%
REGORAFENIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
160 mg 1 times / day multiple, oral
Recommended
unhealthy, 22 to 82 years
Disc. AE: Hepatic failure...
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Other AEs: Pulmonary embolism, Venous thromboembolism...
Other AEs:
Pulmonary embolism (grade 3, 0.8%)
Venous thromboembolism (grade 3, 0.6%)
Arterial thromboembolism (grade 3, 1%)
Sources:
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Other AEs: Palmar-plantar erythrodysaesth., Rash...
Other AEs:
Palmar-plantar erythrodysaesth. (grade 3, 17%)
Rash (grade 3, 5%)
Sources:
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Other AEs: Hemorrhage, Hemorrhage...
Other AEs:
Hemorrhage (grade 1, 17.4%)
Hemorrhage (grade 2, 1.8%)
Hemorrhage (grade 3, 1.4%)
Hemorrhage (grade 5, 0.8%)
Sources:
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Disc. AE: Palmar-plantar erythrodysaesth., Diarrhea...
AEs leading to
discontinuation/dose reduction:
Palmar-plantar erythrodysaesth. (18.2%)
Diarrhea (3.8%)
Hypertension (3.2%)
Fatigue (2%)
Rash (2%)
Mucositis (1.2%)
Abdominal pain (1%)
Asthenia (1%)
Sources:
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Disc. AE: Palmar-plantar erythrodysaesth., Diarrhea...
AEs leading to
discontinuation/dose reduction:
Palmar-plantar erythrodysaesth. (18.8%)
Diarrhea (6.2%)
Pyrexia (4.6%)
Fatigue (4%)
Rash (3.6%)
Hyperbilirubinemia (3.6%)
Decreased appetite (3%)
Asthenia (2.8%)
Hypertension (2.6%)
Abdominal pain (2.4%)
Stomatitis (2.2%)
Dyspnea (2%)
AST increased (1.8%)
Vomiting (1.8%)
Thrombocytopenia (1.6%)
ALT increased (1.4%)
Proteinuria (1.2%)
Sources:
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Disc. AE: General physical health deterioration, Palmar-plantar erythrodysaesth....
AEs leading to
discontinuation/dose reduction:
General physical health deterioration (4%)
Palmar-plantar erythrodysaesth. (1%)
Decreased appetite (1%)
Pneumonia (1%)
Rash (1%)
Sources:
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Other AEs: Decreased appetite, Diarrhea...
Other AEs:
Decreased appetite (grade 3, 5%)
Diarrhea (grade 3, 8%)
Mucositis (grade 3, 4%)
Weight loss (grade 3, <1%)
Infection (grade 3, 9%)
Hypertension (grade 3, 8%)
Pain (grade 3, 3%)
Fever (grade 3, 2%)
Rash (grade 3, 6%)
Hemorrhage (grade 3, 2%)
Headache (grade 3, <1%)
Asthenia (grade 3, 15%)
Sources:
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Other AEs: Dysphonia, Dry mouth...
Other AEs:
Dysphonia
Dry mouth
Decreased appetite
Voice alteration (75%)
Hand and foot skin reaction (58%)
Mucositis (67%)
Diarrhea (58%)
Hypertension (42%)
Fatigue (58%)
Anorexia (42%)
Rash (25%)
Alopecia (25%)
Voice alteration (grade 3, 8%)
Hand and foot skin reaction (grade 3, 42%)
Diarrhea (grade 3, 8%)
Hypertension (grade 3, 25%)
Fatigue (grade 3, 8%)
Rash (grade 3, 8%)
Sources:
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Other AEs: Voice alteration, Hand and foot skin reaction...
Other AEs:
Voice alteration (42%)
Hand and foot skin reaction (67%)
Mucositis (25%)
Diarrhea (50%)
Hypertension (50%)
Fatigue (17%)
Anorexia (50%)
Rash (50%)
Alopecia (33%)
Hand and foot skin reaction (grade 3, 25%)
Mucositis (grade 3, 8%)
Diarrhea (grade 3, 17%)
Hypertension (grade 3, 17%)
Anorexia (grade 3, 8%)
Rash (grade 3, 8%)
Sources:
120 mg 1 times / day multiple, oral
Studied dose
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
DLT: Infection, Hand and foot skin reaction...
Dose limiting toxicities:
Infection (25%)
Hand and foot skin reaction (13%)
Sources:
160 mg 1 times / day multiple, oral
Studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
DLT: Allergic reaction, Vomiting...
Dose limiting toxicities:
Allergic reaction (8%)
Vomiting (8%)
Sources:
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
DLT: Hand and foot skin reaction, Pruritic rash...
Dose limiting toxicities:
Hand and foot skin reaction (17%)
Pruritic rash (8%)
Abdominal pain (8%)
Asthma bronchial (8%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hepatic failure grade 5, 1.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
unhealthy, 22 to 82 years
Venous thromboembolism grade 3, 0.6%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Pulmonary embolism grade 3, 0.8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Arterial thromboembolism grade 3, 1%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Palmar-plantar erythrodysaesth. grade 3, 17%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Rash grade 3, 5%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hemorrhage grade 1, 17.4%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hemorrhage grade 2, 1.8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hemorrhage grade 3, 1.4%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hemorrhage grade 5, 0.8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Abdominal pain 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Asthenia 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Mucositis 1.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Palmar-plantar erythrodysaesth. 18.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Fatigue 2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Rash 2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hypertension 3.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Diarrhea 3.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Proteinuria 1.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
ALT increased 1.4%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Thrombocytopenia 1.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
AST increased 1.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Vomiting 1.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Palmar-plantar erythrodysaesth. 18.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Dyspnea 2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Stomatitis 2.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Abdominal pain 2.4%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hypertension 2.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Asthenia 2.8%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Decreased appetite 3%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hyperbilirubinemia 3.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Rash 3.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Fatigue 4%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Pyrexia 4.6%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Diarrhea 6.2%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Decreased appetite 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Palmar-plantar erythrodysaesth. 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Pneumonia 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Rash 1%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
General physical health deterioration 4%
Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Asthenia grade 3, 15%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Fever grade 3, 2%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hemorrhage grade 3, 2%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Pain grade 3, 3%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Mucositis grade 3, 4%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Decreased appetite grade 3, 5%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Rash grade 3, 6%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Diarrhea grade 3, 8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Hypertension grade 3, 8%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Infection grade 3, 9%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Headache grade 3, <1%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Weight loss grade 3, <1%
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 22 to 82 years
Health Status: unhealthy
Age Group: 22 to 82 years
Sex: M+F
Sources:
Decreased appetite
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Dry mouth
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Dysphonia
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Alopecia 25%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Rash 25%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Anorexia 42%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Hypertension 42%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Diarrhea 58%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Fatigue 58%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Hand and foot skin reaction 58%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Mucositis 67%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Voice alteration 75%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Hypertension grade 3, 25%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Hand and foot skin reaction grade 3, 42%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Diarrhea grade 3, 8%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Fatigue grade 3, 8%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Rash grade 3, 8%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Voice alteration grade 3, 8%
220 mg 1 times / day multiple, oral
Highest studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Fatigue 17%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Mucositis 25%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Alopecia 33%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Voice alteration 42%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Anorexia 50%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Diarrhea 50%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Hypertension 50%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Rash 50%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Hand and foot skin reaction 67%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Diarrhea grade 3, 17%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Hypertension grade 3, 17%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Hand and foot skin reaction grade 3, 25%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Anorexia grade 3, 8%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Mucositis grade 3, 8%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Rash grade 3, 8%
160 mg 1 times / day multiple, oral
MTD|Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Hand and foot skin reaction 13%
DLT
120 mg 1 times / day multiple, oral
Studied dose
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Infection 25%
DLT
120 mg 1 times / day multiple, oral
Studied dose
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Allergic reaction 8%
DLT
160 mg 1 times / day multiple, oral
Studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Vomiting 8%
DLT
160 mg 1 times / day multiple, oral
Studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Health Status: unhealthy
Age Group: median age 60 years
Sex: M+F
Sources:
Hand and foot skin reaction 17%
DLT
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Abdominal pain 8%
DLT
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Asthma bronchial 8%
DLT
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
Pruritic rash 8%
DLT
220 mg 1 times / day multiple, oral
Studied dose
Dose: 220 mg, 1 times / day
Route: oral
Route: multiple
Dose: 220 mg, 1 times / day
Sources:
unhealthy, median age 60 years
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
yes [IC50 44.7 uM]
yes [Ki 0.6 uM]
yes [Ki 11.1 uM]
yes [Ki 16.4 uM]
yes [Ki 2.1 uM]
yes [Ki 3 uM]
yes [Ki 4.7 uM]
yes [Ki 7.8 uM]
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
major
yes (co-administration study)
Comment: The administration of ketoconazole 400 mg daily for 18 days with a single 160 mg dose of regorafenib increased the mean AUC of regorafenib by 33% and decreased the mean AUC of M2 and M5 each by 93%. The administration of rifampin 600 mg daily for 9 days with a single 160 mg dose of regorafenib decreased the mean AUC of regorafenib by 50% and increased the mean AUC of M5 by 264%; the mean AUC of M2 was similar with and without rifampin.
Page: -
no
no
no
no
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity.
2011 Jul 1
Small molecule inhibitors of BRAF in clinical trials.
2012 Jan 15
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

160 mg Stivarga orally, once daily for the first 21 days of each 28-day cycle. Take with a low-fat meal.
Route of Administration: Oral
For the migration inhibition assay, human lymphatic endothelial cells (LECs) were grown overnight on a gelatin-coated six-well plate, serum starved for 6 hr in EBM-2 media containing 0.1% BSA and treated with 100 nmol/L regorafenib for 1 hr. Regorafenib inhibited the proliferation of 19 cell lines derived from human colon cancers, with IC50 values ranging from 2.6 to 10 umol/L.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:08:07 UTC 2021
Edited
by admin
on Fri Jun 25 21:08:07 UTC 2021
Record UNII
MGN125FS9D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
REGORAFENIB MONOHYDRATE
Common Name English
REGORAFENIB MONOHYDRATE [EP MONOGRAPH]
Common Name English
BAY-73-4506 MONOHYDRATE
Code English
2-PYRIDINECARBOXAMIDE, 4-(4-((((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)AMINO)CARBONYL)AMINO)-3-FLUOROPHENOXY)-N-METHYL-, HYDRATE (1:1)
Systematic Name English
REGORAFENIB HYDRATE [JAN]
Common Name English
BAY-734506 MONOHYDRATE
Code English
REGORAFENIB HYDRATE
JAN  
Common Name English
Code System Code Type Description
PUBCHEM
24768591
Created by admin on Fri Jun 25 21:08:07 UTC 2021 , Edited by admin on Fri Jun 25 21:08:07 UTC 2021
PRIMARY
RXCUI
1371319
Created by admin on Fri Jun 25 21:08:07 UTC 2021 , Edited by admin on Fri Jun 25 21:08:07 UTC 2021
PRIMARY RxNorm
CAS
1019206-88-2
Created by admin on Fri Jun 25 21:08:07 UTC 2021 , Edited by admin on Fri Jun 25 21:08:07 UTC 2021
PRIMARY
EPA CompTox
1019206-88-2
Created by admin on Fri Jun 25 21:08:07 UTC 2021 , Edited by admin on Fri Jun 25 21:08:07 UTC 2021
PRIMARY
FDA UNII
MGN125FS9D
Created by admin on Fri Jun 25 21:08:07 UTC 2021 , Edited by admin on Fri Jun 25 21:08:07 UTC 2021
PRIMARY
DRUG BANK
DBSALT001750
Created by admin on Fri Jun 25 21:08:07 UTC 2021 , Edited by admin on Fri Jun 25 21:08:07 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY