PAMAPIMOD

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20F2N4O4
Molecular Weight	406.3833
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)C(OC2=CC=C(F)C=C2F)=CC3=CN=C(NC(CCO)CCO)N=C13

InChI

InChIKey=JYYLVUFNAHSSFE-UHFFFAOYSA-N

InChI=1S/C19H20F2N4O4/c1-25-17-11(10-22-19(24-17)23-13(4-6-26)5-7-27)8-16(18(25)28)29-15-3-2-12(20)9-14(15)21/h2-3,8-10,13,26-27H,4-7H2,1H3,(H,22,23,24)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18776065 | https://www.ncbi.nlm.nih.gov/pubmed/20666701

Pamapimod (R-1503, Ro4402257) is a potent and selective inhibitor of p38 mitogen-activated protein kinase alpha. The preclinical data support the conclusion that pamapimod has the ability to inhibit the signs and symptoms of rheumatoid arthritis and other autoimmune diseases. Pamapimod was being developed for use in the treatment of rheumatoid arthritis. There is no clear-cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis but it does cause adverse effects. It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
MAP kinase p38 alpha 35 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18776065	Inhibitor 8297		0.014 µM [IC50]
MAP kinase p38 beta 11 Target ID: CHEMBL3961 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18776065	Inhibitor 8297		0.48 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20100913 https://www.ncbi.nlm.nih.gov/pubmed/19357113	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
6.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20100913	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PAMAPIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
21.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20100913	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PAMAPIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20100913	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PAMAPIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Co-administed with:: methotrexate(orally once a week, commencing at 7.5 mg (three 2.5-mg tablets) on day 1) Sources: https://pubmed.ncbi.nlm.nih.gov/19180516	unhealthy n = 48 Health Status: unhealthy Condition: rheumatoid arthritis Sex: M+F Food Status: UNKNOWN Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/19180516	Disc. AE: rheumatoid arthritis flare, gastrointestinal infection... AEs leading to discontinuation/dose reduction: rheumatoid arthritis flare (1 pt) gastrointestinal infection (1 pt) Gastrointestinal disorder (3 patients) skin disorders (2 patients) Elevated liver enzyme levels (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/19180516

AEs

AE	Significance	Dose	Population
gastrointestinal infection	1 pt Disc. AE	300 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Co-administed with:: methotrexate(orally once a week, commencing at 7.5 mg (three 2.5-mg tablets) on day 1) Sources: https://pubmed.ncbi.nlm.nih.gov/19180516	unhealthy n = 48 Health Status: unhealthy Condition: rheumatoid arthritis Sex: M+F Food Status: UNKNOWN Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/19180516
rheumatoid arthritis flare	1 pt Disc. AE	300 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Co-administed with:: methotrexate(orally once a week, commencing at 7.5 mg (three 2.5-mg tablets) on day 1) Sources: https://pubmed.ncbi.nlm.nih.gov/19180516	unhealthy n = 48 Health Status: unhealthy Condition: rheumatoid arthritis Sex: M+F Food Status: UNKNOWN Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/19180516
skin disorders	2 patients Disc. AE	300 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Co-administed with:: methotrexate(orally once a week, commencing at 7.5 mg (three 2.5-mg tablets) on day 1) Sources: https://pubmed.ncbi.nlm.nih.gov/19180516	unhealthy n = 48 Health Status: unhealthy Condition: rheumatoid arthritis Sex: M+F Food Status: UNKNOWN Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/19180516
Elevated liver enzyme levels	3 patients Disc. AE	300 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Co-administed with:: methotrexate(orally once a week, commencing at 7.5 mg (three 2.5-mg tablets) on day 1) Sources: https://pubmed.ncbi.nlm.nih.gov/19180516	unhealthy n = 48 Health Status: unhealthy Condition: rheumatoid arthritis Sex: M+F Food Status: UNKNOWN Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/19180516
Gastrointestinal disorder	3 patients Disc. AE	300 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Co-administed with:: methotrexate(orally once a week, commencing at 7.5 mg (three 2.5-mg tablets) on day 1) Sources: https://pubmed.ncbi.nlm.nih.gov/19180516	unhealthy n = 48 Health Status: unhealthy Condition: rheumatoid arthritis Sex: M+F Food Status: UNKNOWN Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/19180516

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00DBO0	https://www.1pchem.com/search?query=1P00DBO0
ApexBio Technology	B6188	https://www.apexbt.com/catalogsearch/result/?q=B6188
AstaTech	40690	http://astatechinc.com/CPSResult.php?CRNO=40690
BOC Sciences	449811-01-2	http://www.bocsci.com/description.asp?cas=449811-01-2
Cayman Chemical	20971	http://www.caymanchem.com/app/template/Product.vm/catalog/20971
Chem Scene	CS-5965	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5965
ChemShuttle	158509	https://www.chemshuttle.com/catalogsearch/result/?q=158509
Excenen	EX-A1084	http://www.excenen.com/searchresultlist.php?id=EX-A1084
KeyOrganics	AS-56094	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56094
MedChem Express	HY-10405	https://www.medchemexpress.com/search.html?q=HY-10405&ft=&fa=&fp=
MolPort	MolPort-044-560-378	https://www.molport.com/shop/molecule-link/MolPort-044-560-378
Molnova	M14535	https://www.molnova.com/en/serch-list.html?keywords=M14535
MuseChem	I003588	https://www.musechem.com/product/I003588.html
Selleck Chemicals	S8125	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8125
ShangHai Biochempartner	BCP17491	http://www.biochempartner.com/search_BCP17491
TargetMol	T6927	https://www.targetmol.com/search?keyword=T6927
Toronto Research Chemicals	P167500	https://www.trc-canada.com/product-detail/?CatNum=P167500
eMolecules	31593195	https://orderbb.emolecules.com/search/#?query=31593195
mcule	MCULE-2298759294	https://mcule.com/MCULE-2298759294/

PubMed

Title	Date	PubMed
Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity.	2008 Dec	18776065
Clinically relevant advances in rheumatoid arthritis therapy.	2009 Sep 14	20948712
Differential effects of p38MAP kinase inhibitors on the expression of inflammation-associated genes in primary, interleukin-1beta-stimulated human chondrocytes.	2010 Jul	20590617
Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders.	2010 Mar 25	19950901
Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?	2010 Oct	20666701

Patents

Sample Use Guides

In Vivo Use Guide

Rheumatoid arthritis patients receiving stable doses of methotrexate were randomised to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily) or matching placebo.

Route of Administration: Oral

In Vitro Use Guide

After LPS stimulation of the human myelomonocytic cell line (THP-1), secretion of TNF was inhibited by pamapimod, with an EC50 of 0.025 uM. Pamapimod suppressed TNF- and IL-1 production in whole blood, with EC50 values of 0.40 and 0.10 uM, respectively.

Name

Type

Language

PAMAPIMOD

Official Name

English

R1503

Code

English

6-(2,4-Difluorophenoxy)-2-{[3-hydroxy-1-(2-hydroxyethyl)propyl]amino}-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one

Systematic Name

English

Pamapimod [WHO-DD]

Common Name

English

pamapimod [INN]

Common Name

English

R-1503

Code

English

PAMAPIMOD [USAN]

Common Name

English

RO-4402257

Code

English

RO 4402257

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C2149