PIMASERTIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H15FIN3O3
Molecular Weight	431.2008
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=VIUAUNHCRHHYNE-JTQLQIEISA-N

InChI=1S/C15H15FIN3O3/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)/t10-/m0/s1

HIDE SMILES / InChI

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20331454
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

Targets

Primary Target	Pharmacology	Condition	Potency
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 4 Target ID: CHEMBL2111289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20331454	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Metastasis malignant cutaneous melanoma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT01693068	Primary	Approved 8429	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT01936363	Primary	Phase II 1132	Unknown Approved Use Unknown
Pancreatic adenocarcinoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT01016483	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy.	2011 Jan 15	21118963

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

AS703026 (PIMASERTIB) (10 μM) effectively inhibits the ERK pathway, proliferation, and transformation in human DLD-1 colorectal cancer cells what carry a mutant allele of K-Ras (D-MUT).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 20:15:38 GMT 2023` Edited by `admin` on `Fri Dec 15 20:15:38 GMT 2023`
Record UNII	6ON9RK82AL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIMASERTIB

Official Name

English

pimasertib [INN]

Common Name

English

MSC-1936369A

Code

English

MSC-1936369

Common Name

English

PIMASERTIB [USAN]

Common Name

English

AS 703026

Code

English

EMD-1036239

Code

English

N-[(2S)-2,3-Dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]pyridine-4-carboxamide

Systematic Name

English

Pimasertib [WHO-DD]

Common Name

English

4-PYRIDINECARBOXAMIDE, N-((2S)-2,3-DIHYDROXYPROPYL)-3-((2-FLUORO-4-IODOPHENYL)AMINO)-

Systematic Name

English

EMD 1036239

Code

English

AS-703026

Code

English

AS703026

Code

English

MSC1936369A

Code

English

G-02443714

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C69145