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
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
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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/18952427https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=456780Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18952427https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=456780
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
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2964 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18952427 |
1.0 nM [Ki] | ||
Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18952427 |
1.0 nM [Ki] | ||
Target ID: CHEMBL3587 Sources: http://pubs.acs.org/doi/suppl/10.1021/ml300049d |
0.6 nM [IC50] | ||
Target ID: CHEMBL2964 |
1.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
462 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1784 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20215549/ |
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
Dose | Population | Adverse 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) Sources: 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) |
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) Sources: Dizziness (grade 3, 1 pt) |
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... |
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) Other AEs:fatigue (1 pt) Hallucinations (1 pt) Confusional state (grade 3, 8%) Sources: 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%) |
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) Sources: Left ventricular ejection fraction decreased (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: |
Other AEs: Optic neuropathy, rash... Other AEs: Optic neuropathy (1 pt) Sources: rash (grade 3, 1 pt) unsteady gait (grade 3, 1 pt) |
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) Sources: diarrhea (grade 3, 1 pt) syncope (grade 3, 1 pt) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
Title | Date | PubMed |
---|---|---|
A phase II study of PD-0325901, an oral MEK inhibitor, in previously treated patients with advanced non-small cell lung cancer. | 2010 Apr 15 |
|
The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition. | 2012 Apr 10 |
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PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. | 2014 Oct 9 |
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Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells. | 2015 Aug 18 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02022982
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18651802
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
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