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
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 May	20331454
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
MEK inhibitors as a chemotherapeutic intervention in multiple myeloma.	2013 Mar 22	23524590

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 UTC 2023` Edited by `admin` on `Fri Dec 15 20:15:38 UTC 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