Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C15H15FIN3O3.ClH |
| Molecular Weight | 467.662 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.OC[C@@H](O)CNC(=O)C1=C(NC2=C(F)C=C(I)C=C2)C=NC=C1
InChI
InChIKey=HIEXZUXKTABHCP-PPHPATTJSA-N
InChI=1S/C15H15FIN3O3.ClH/c16-12-5-9(17)1-2-13(12)20-14-7-18-4-3-11(14)15(23)19-6-10(22)8-21;/h1-5,7,10,20-22H,6,8H2,(H,19,23);1H/t10-;/m0./s1
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C15H15FIN3O3 |
| Molecular Weight | 431.2008 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: description was created based on several sources, including
http://ar2014.merckgroup.com/management-report/fundamental-information-about-the-group/research-and-development-at-merck
Curator's Comment: description was created based on several sources, including
http://ar2014.merckgroup.com/management-report/fundamental-information-about-the-group/research-and-development-at-merck
Pimasertib) (N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]isonicotinamide hydrochloride; AS703026), a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2. It binds to MEK1/2 in an allosteric site that is distinct from, yet in close proximity to, the ATP binding site. Binding to this allosteric site prevents the activation of MEK1/2. Pimasertib continues to be investigated in patients with NRAS mutant malignant melanoma in a Phase II trial. This drug was discontinued in a combination with SAR245409 for Phase II study in low-grade serous ovarian cancer. This decision was based on the results of a futility analysis, conducted by the IDMC, which indicated that the trial was no longer expected to achieve its objective of showing a meaningful difference between the efficacies of the combination compared with pimasertib alone. The further development of pimasertib in pancreatic cancer was also discontinued, as a Phase II study in this indication did not reach its primary endpoint of prolongation of progression-free survival
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
283.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26657199/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
261.83 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26657199/ |
60 mg 2 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
12.7 pg × eq/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
2 μg single, intravenous dose: 2 μg route of administration: Intravenous experiment type: SINGLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
265 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
774 ng × eq/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1160.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26657199/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
952.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26657199/ |
60 mg 2 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.036 ng × eq × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
2 μg single, intravenous dose: 2 μg route of administration: Intravenous experiment type: SINGLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
937 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
5318 ng × eq × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3.019 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26657199/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.53 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26657199/ |
60 mg 2 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
2 μg single, intravenous dose: 2 μg route of administration: Intravenous experiment type: SINGLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
6.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
6.7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27483391/ |
PIMASERTIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
45 mg 2 times / day multiple, oral MTD Dose: 45 mg, 2 times / day Route: oral Route: multiple Dose: 45 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
|
45 mg 2 times / day multiple, oral Studied dose Dose: 45 mg, 2 times / day Route: oral Route: multiple Dose: 45 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: |
DLT: Diarrhea... |
60 mg 2 times / day multiple, oral Studied dose Dose: 60 mg, 2 times / day Route: oral Route: multiple Dose: 60 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Hypokalemia, Stomatitis... Dose limiting toxicities: Hypokalemia (grade 3, 33.3%) Sources: Stomatitis (33.3%) Muscle weakness (33.3%) |
30 mg 2 times / day multiple, oral Studied dose Dose: 30 mg, 2 times / day Route: oral Route: multiple Dose: 30 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Retinal detachment... Dose limiting toxicities: Retinal detachment (grade 1, 33.3%) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Diarrhea | grade 2, 100% DLT, Disc. AE |
45 mg 2 times / day multiple, oral Studied dose Dose: 45 mg, 2 times / day Route: oral Route: multiple Dose: 45 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: |
| Muscle weakness | 33.3% DLT, Disc. AE |
60 mg 2 times / day multiple, oral Studied dose Dose: 60 mg, 2 times / day Route: oral Route: multiple Dose: 60 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Stomatitis | 33.3% DLT, Disc. AE |
60 mg 2 times / day multiple, oral Studied dose Dose: 60 mg, 2 times / day Route: oral Route: multiple Dose: 60 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Hypokalemia | grade 3, 33.3% DLT, Disc. AE |
60 mg 2 times / day multiple, oral Studied dose Dose: 60 mg, 2 times / day Route: oral Route: multiple Dose: 60 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Retinal detachment | grade 1, 33.3% DLT, Disc. AE |
30 mg 2 times / day multiple, oral Studied dose Dose: 30 mg, 2 times / day Route: oral Route: multiple Dose: 30 mg, 2 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| MEK inhibitors as a chemotherapeutic intervention in multiple myeloma. | 2013-03-22 |
|
| MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy. | 2011-01-15 |
|
| Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo. | 2010-05 |
Patents
Sample Use Guides
Pimasertib will be administered as oral capsule at a dose of 60 mg twice daily continuously. Treatment will consist of repeated 21-day cycles which will be continued until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever comes first.
Route of Administration:
Oral
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 21:08:43 GMT 2025
by
admin
on
Mon Mar 31 21:08:43 GMT 2025
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| Record UNII |
6GS1ULF5HV
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| Record Status |
Validated (UNII)
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| Record Version |
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-
Download
| Name | Type | Language | ||
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Official Name | English | ||
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Preferred Name | English | ||
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Systematic Name | English | ||
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Code | English | ||
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Common Name | English | ||
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Code | English | ||
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Code | English |
| Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
297909
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FDA ORPHAN DRUG |
328110
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EU-Orphan Drug |
EU/3/10/824
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| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
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52918382
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PRIMARY | |||
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EU/3/09/685(POSITIVE)
Created by
admin on Mon Mar 31 21:08:43 GMT 2025 , Edited by admin on Mon Mar 31 21:08:43 GMT 2025
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PRIMARY | Treatment of pancreatic cancer 8/10/2009 Positive | ||
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EU/3/10/824 (POSITIVE)
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admin on Mon Mar 31 21:08:43 GMT 2025 , Edited by admin on Mon Mar 31 21:08:43 GMT 2025
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PRIMARY | Treatment of acute myeloid leukaemia 17/12/2010 Positive | ||
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DTXSID60154058
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PRIMARY | |||
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ZZ-117
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1236361-78-6
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100000155425
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SUB129490
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C166935
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6GS1ULF5HV
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PRIMARY |
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