PIMASERTIB HYDROCHLORIDE

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

Structure Search

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

HIDE SMILES / InChI

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
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).

Name

Type

Language

PIMASERTIB HYDROCHLORIDE

Official Name

English

4-PYRIDINECARBOXAMIDE, N-((2S)-2,3-DIHYDROXYPROPYL)-3-((2-FLUORO-4-IODOPHENYL)AMINO)-, HYDROCHLORIDE (1:1)

Systematic Name

English

MSC1936369B

Code

English

PIMASERTIB HYDROCHLORIDE [USAN]

Common Name

English

EMD-1036950

Code

English

MSC-1936369B

Code

English

EMD 1036950

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

297909