U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C16H14F3IN2O4
Molecular Weight 482.193
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MIRDAMETINIB

SMILES

OC[C@@H](O)CONC(=O)C1=C(NC2=C(F)C=C(I)C=C2)C(F)=C(F)C=C1

InChI

InChIKey=SUDAHWBOROXANE-SECBINFHSA-N
InChI=1S/C16H14F3IN2O4/c17-11-3-2-10(16(25)22-26-7-9(24)6-23)15(14(11)19)21-13-4-1-8(20)5-12(13)18/h1-5,9,21,23-24H,6-7H2,(H,22,25)/t9-/m1/s1

HIDE SMILES / InChI

Molecular Formula C16H14F3IN2O4
Molecular Weight 482.193
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20332327 | https://www.ncbi.nlm.nih.gov/pubmed/18952427

PD 0325901 is an orally bioavailable, synthetic organic molecule targeting mitogen-activated protein kinase kinase (MAPK/ERK kinase or MEK) with potential antineoplastic activity. MEK inhibitor PD325901, a derivative of MEK inhibitor CI-1040, selectively binds to and inhibits MEK, which may result in the inhibition of the phosphorylation and activation of MAPK/ERK and the inhibition of tumor cell proliferation. Clinical trials of monotherapy PD0325901 agains non-small cell lung cancer and colorectal cancer did not reach efficacy end point. For subsequent studies KRAS-positive patients with non-small cell lung cancer and colorectal cancer were selected, and PD0325901 was evaluated in combination with pablociclib and dacomtinib. PD0325901 is evaluated in phase II clinical trials against neurofibromatosis.

Originator

Curator's Comment: # Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
462 μg/mL
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
706 ng/mL
15 mg 2 times / day multiple, oral
dose: 15 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
839 ng/mL
15 mg 2 times / day multiple, oral
dose: 15 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
972 ng/mL
20 mg 2 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
766 ng/mL
20 mg 2 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1640 ng/mL
30 mg 2 times / day multiple, oral
dose: 30 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
198 ng/mL
4 mg 2 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1784 ng × h/mL
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2840 ng × h/mL
15 mg 2 times / day multiple, oral
dose: 15 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3062 ng × h/mL
15 mg 2 times / day multiple, oral
dose: 15 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3235 ng × h/mL
20 mg 2 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3497 ng × h/mL
20 mg 2 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6215 ng × h/mL
30 mg 2 times / day multiple, oral
dose: 30 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
691 ng × h/mL
4 mg 2 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.28 h
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8.7 h
15 mg 2 times / day multiple, oral
dose: 15 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.2 h
15 mg 2 times / day multiple, oral
dose: 15 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.6 h
20 mg 2 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7.7 h
20 mg 2 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.7 h
30 mg 2 times / day multiple, oral
dose: 30 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.5 h
4 mg 2 times / day multiple, oral
dose: 4 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PD-0325901 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
Other AEs: Diarrhea, Blurred vision...
Other AEs:
Diarrhea (all grades, 3 patients)
Blurred vision (all grades, 1 pt)
ataxia (all grades, 1 pt)
dizziness (all grades, 1 pt)
Rash (all grades, 2 patients)
Fatigue (all grades, 2 patients)
Nausea (all grades, 1 pt)
Gait disturbance (all grades, 1 pt)
Visual disturbance (all grades, 2 patients)
Sources:
10 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FED
Population Size: 13
Sources:
DLT: confusion...
Dose limiting toxicities:
confusion (grade 3, 1 pt)
Sources:
10 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
n = 7
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
DLT: Confusion, Dizziness...
Dose limiting toxicities:
Confusion (grade 3, 1 pt)
Dizziness (grade 3, 1 pt)
Sources:
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
DLT: rash...
Dose limiting toxicities:
rash (grade 3, 1 pt)
Sources:
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Disc. AE: Blurred vision, fatigue...
Other AEs: Confusional state, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Blurred vision (1 pt)
fatigue (1 pt)
Hallucinations (1 pt)
Other AEs:
Confusional state (grade 3, 8%)
Diarrhea (grade 3, 8%)
Peripheral edema (grade 1-2, 15%)
Epistaxis (grade 1-2, 15%)
Dyspnea (grade 3, 8%)
Nausea (grade 1-2, 38%)
Rash (grade 3, 8%)
Asthenia (grade 1-2, 8%)
Dermatitis acneiform (grade 1-2, 8%)
Myalgia (grade 1-2, 8%)
Vomiting (grade 1-2, 38%)
Dry mouth (grade 1-2, 15%)
Dyspepsia (grade 1-2, 15%)
Facial edema (grade 1-2, 15%)
headache (grade 1-2, 8%)
Weight gain (grade 1-2, 8%)
Sources:
20 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
DLT: rash, Left ventricular ejection fraction decreased...
Dose limiting toxicities:
rash (grade 3, 1 pt)
Left ventricular ejection fraction decreased (grade 3, 1 pt)
Sources:
20 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
n = 5
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
Other AEs: Optic neuropathy, rash...
Other AEs:
Optic neuropathy (1 pt)
rash (grade 3, 1 pt)
unsteady gait (grade 3, 1 pt)
Sources:
30 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 30 mg, 2 times / day
Route: oral
Route: multiple
Dose: 30 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
DLT: rash, diarrhea...
Dose limiting toxicities:
rash (grade 3, 1 pt)
diarrhea (grade 3, 1 pt)
syncope (grade 3, 1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
Blurred vision all grades, 1 pt
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
Gait disturbance all grades, 1 pt
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
Nausea all grades, 1 pt
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
ataxia all grades, 1 pt
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
dizziness all grades, 1 pt
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
Fatigue all grades, 2 patients
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
Rash all grades, 2 patients
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
Visual disturbance all grades, 2 patients
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
Diarrhea all grades, 3 patients
15 mg 2 times / day multiple, oral
MTD
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 4
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FASTED
Population Size: 4
Sources:
confusion grade 3, 1 pt
DLT
10 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: FED
Population Size: 13
Sources:
Confusion grade 3, 1 pt
DLT
10 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
n = 7
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
Dizziness grade 3, 1 pt
DLT
10 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: multiple
Dose: 10 mg, 2 times / day
Sources:
unhealthy
n = 7
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
rash grade 3, 1 pt
DLT
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
Blurred vision 1 pt
Disc. AE
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Hallucinations 1 pt
Disc. AE
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
fatigue 1 pt
Disc. AE
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Dry mouth grade 1-2, 15%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Dyspepsia grade 1-2, 15%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Epistaxis grade 1-2, 15%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Facial edema grade 1-2, 15%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Peripheral edema grade 1-2, 15%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Nausea grade 1-2, 38%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Vomiting grade 1-2, 38%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Asthenia grade 1-2, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Dermatitis acneiform grade 1-2, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Myalgia grade 1-2, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Weight gain grade 1-2, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
headache grade 1-2, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Confusional state grade 3, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Diarrhea grade 3, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Dyspnea grade 3, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Rash grade 3, 8%
15 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 15 mg, 2 times / day
Route: oral
Route: multiple
Dose: 15 mg, 2 times / day
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: NSCLC
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Left ventricular ejection fraction decreased grade 3, 1 pt
DLT
20 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
rash grade 3, 1 pt
DLT
20 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
Optic neuropathy 1 pt
20 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
n = 5
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
rash grade 3, 1 pt
20 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
n = 5
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
unsteady gait grade 3, 1 pt
20 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources:
unhealthy
n = 5
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources:
diarrhea grade 3, 1 pt
DLT
30 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 30 mg, 2 times / day
Route: oral
Route: multiple
Dose: 30 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
rash grade 3, 1 pt
DLT
30 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 30 mg, 2 times / day
Route: oral
Route: multiple
Dose: 30 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
syncope grade 3, 1 pt
DLT
30 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 30 mg, 2 times / day
Route: oral
Route: multiple
Dose: 30 mg, 2 times / day
Sources:
unhealthy
n = 6
Health Status: unhealthy
Condition: Advanced Cancers
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources:
PubMed

PubMed

TitleDatePubMed
Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance.
2012 May 10
Pan-FGFR inhibition leads to blockade of FGF23 signaling, soft tissue mineralization, and cardiovascular dysfunction.
2013 Oct
U0126, a mitogen-activated protein kinase kinase 1 and 2 (MEK1 and 2) inhibitor, selectively up-regulates main isoforms of CYP3A subfamily via a pregnane X receptor (PXR) in HepG2 cells.
2014 Dec
PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies.
2014 Oct 9
Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells.
2015 Aug 18
Patents

Sample Use Guides

In clinical trials against KRAS-mutant NSCLC PD-0325901 was administered orally twice daily, 3 weeks out of every 4 in each cycle. The initial dose for phase 1 of the study was be 2 mg twice daily.
Route of Administration: Oral
MTT assay was used to evaluate effect of PD-0325901 on tumor cell proliferation. Briefly, cells (800/well) were seeded into a 96-well plate, and after 5 days of treatment with the indicated concentrations of PD0325901, 10 μL of 5 mg/mL MTT (Sigma) was added to cell culture, followed by addition of 100 μL of 10% sodium dodecyl sulfate (SDS) solution 4 hours later. After incubation for another 12 hours, the plates were read on a microplate reader at a test wavelength of 570 nm and a reference wavelength of 670 nm. PD-0325901 demonstrated potent inhibition of cells harboring BRAF or RAS mutations (KAK1, KAT5, KAT7, KAT10, NPA, DRO, and C643) with IC50 ranging from 0.059 to 0.783 uM.
Substance Class Chemical
Created
by admin
on Sat Dec 16 04:18:35 UTC 2023
Edited
by admin
on Sat Dec 16 04:18:35 UTC 2023
Record UNII
86K0J5AK6M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PD-0325901
Preferred Name English
MIRDAMETINIB
USAN   INN  
Official Name English
Mirdametinib [WHO-DD]
Common Name English
BENZAMIDE, N-((2R)-2,3-DIHYDROXYPROPOXY)-3,4-DIFLUORO-2-((2-FLUORO-4-IODOPHENYL)AMINO)-
Systematic Name English
N-((2R)-2,3-DIHYDROXYPROPOXY)-3,4-DIFLUORO-2-((2-FLUORO-4-IODOPHENYL)AMINO)-BENZAMIDE
Systematic Name English
N-(((R)-2,3-DIHYDROXYPROPYL)OXY)-3,4-DIFLUORO-2-((2-FLUORO-4-IODOPHENYL)AMINO)BENZAMIDE N-((2R)-2,3-DIHYDROXYPROPOXY)-3,4-DIFLUORO-2-(2-FLUORO-4-IODOANILINO)BENZAMIDE
Systematic Name English
N-(((R)-2,3-DIHYDROXYPROPYL)OXY)-3,4-DIFLUORO-2-((2-FLUORO-4-IODOPHENYL)AMINO)BENZAMIDE
Systematic Name English
mirdametinib [INN]
Common Name English
PD 0325901
Common Name English
PD 901
Common Name English
(-)-N-(((R)-2,3-DIHYDROXYPROPYL)OXY)-3,4-DIFLUORO-2-((2-FLUORO-4-IODOPHENYL)AMINO)BENZAMIDE
Systematic Name English
PD 03525901
Common Name English
MIRDAMETINIB [USAN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 655618
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
Code System Code Type Description
USAN
GH-09
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
EVMPD
SUB197066
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
FDA UNII
86K0J5AK6M
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
CAS
391210-10-9
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
ChEMBL
CHEMBL507361
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
SMS_ID
100000182743
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
PUBCHEM
9826528
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
CHEBI
88249
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
EPA CompTox
DTXSID0044024
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
MESH
C506614
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
NCI_THESAURUS
C52195
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
INN
11299
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
DRUG BANK
DB07101
Created by admin on Sat Dec 16 04:18:35 UTC 2023 , Edited by admin on Sat Dec 16 04:18:35 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY