RO-4987655

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H19F3IN3O5
Molecular Weight	565.2816
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OCCONC(=O)C1=CC(CN2OCCCC2=O)=C(F)C(F)=C1NC3=CC=C(I)C=C3F

InChI

InChIKey=FIMYFEGKMOCQKT-UHFFFAOYSA-N

InChI=1S/C20H19F3IN3O5/c21-14-9-12(24)3-4-15(14)25-19-13(20(30)26-31-7-5-28)8-11(17(22)18(19)23)10-27-16(29)2-1-6-32-27/h3-4,8-9,25,28H,1-2,5-7,10H2,(H,26,30)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21316218
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19934286 | https://clinicaltrials.gov/ct2/show/NCT00817518

RO4987655 is a highly selective non-competitive small molecule inhibitor of MEK. RO4987655 has a strong anti-proliferation efficacy in various tumor cells including COLO205, HT29, QG56, MIA and C32 with IC50 values of 0.86nM, 1.7nM, 9.5nM, 3.3nM and 8.4nM, respectively. In addition, RO4987655 is found to have antitumor activity in a wide range of human cancer xenograft models. In the HT-29 human colon cancer xenograft, RO4987655 shows a strong inhibition of pERK formation as well as tumor regression. RO4987655 shows clinical activity in both patients with BRAF wild-type melanoma and BRAF V600-mutated melanoma. It is also efficacious in patients with KRAS-mutated non-small cell lung cancer but not KRAS-mutated colorectal cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dual specificity mitogen-activated protein kinase kinase 1 20 Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21316218	Inhibitor 8297		0.24 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced solid cancer 28 Sources: https://clinicaltrials.gov/ct2/show/NCT00817518	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
425 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	8.5 mg 2 times / day multiple, oral dose: 8.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
601 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	10.5 mg 2 times / day multiple, oral dose: 10.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
530 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	8.5 mg 2 times / day steady-state, oral dose: 8.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
399 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	10.5 mg 2 times / day steady-state, oral dose: 10.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
1660 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	8.5 mg 2 times / day multiple, oral dose: 8.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2282 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	10.5 mg 2 times / day multiple, oral dose: 10.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2577 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	8.5 mg 2 times / day steady-state, oral dose: 8.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2638 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	10.5 mg 2 times / day steady-state, oral dose: 10.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
3.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	8.5 mg 2 times / day multiple, oral dose: 8.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	10.5 mg 2 times / day multiple, oral dose: 10.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	8.5 mg 2 times / day steady-state, oral dose: 8.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
8.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22767668	10.5 mg 2 times / day steady-state, oral dose: 10.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RO-4987655 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00GUMS	https://www.1pchem.com/search?query=1P00GUMS
AK Scientific	4014AH	https://aksci.com/item_detail.php?cat=4014AH
AK Scientific	SYN1188	https://aksci.com/item_detail.php?cat=SYN1188
Angene	AGN-PC-0VDA4K	http://www.angenechemical.com/productshow/AGN-PC-0VDA4K.html
ApexBio Technology	B3261	https://www.apexbt.com/catalogsearch/result/?q=B3261
BLD Pharm	BD338926	http://www.bldpharm.com/search/Search.html?keyword=BD338926
Cayman Chemical	19488	http://www.caymanchem.com/app/template/Product.vm/catalog/19488
Chem Scene	CS-2715	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2715
ChemShuttle	157290	https://www.chemshuttle.com/catalogsearch/result/?q=157290
Excenen	EX-A2312	http://www.excenen.com/searchresultlist.php?id=EX-A2312
KeyOrganics	AS-16322	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16322
MedChem Express	HY-14719	https://www.medchemexpress.com/search.html?q=HY-14719&ft=&fa=&fp=
MolPort	MolPort-029-944-725	https://www.molport.com/shop/molecule-link/MolPort-029-944-725
Molnova	M16357	https://www.molnova.com/en/serch-list.html?keywords=M16357
MuseChem	I005266	https://www.musechem.com/product/I005266.html
ShangHai Biochempartner	BCP12182	http://www.biochempartner.com/search_BCP12182
Synthonix	SL100176	http://www.synthon-lab.com/search.php?cas_or_id=SL100176&cas_id_field=1
TargetMol	T5412	https://www.targetmol.com/search?keyword=T5412
W&J PharmaChem	50C1664660	http://wjpharmachem.com/new/searcht.php?keyword=50C1664660
eMolecules	46019658	https://orderbb.emolecules.com/search/#?query=46019658
mcule	MCULE-2757606055	https://mcule.com/MCULE-2757606055/

PubMed

Title	Date	PubMed
Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent.	2011 Mar 15	21316218

Patents

Sample Use Guides

In Vivo Use Guide

Administered po daily for 28 days, at escalating doses , with a starting dose of 1mg

Route of Administration: Oral

In Vitro Use Guide

The growth inhibitory activities against cancer cells were measured using Cell Counting Kit-8 (Dojindo Laboratories). Human colon cancer cell line HT-29 obtained from American Type Culture Collection (Virginia, USA) and human non-small cell lung carcinoma cell line QG56 obtained from Immuno-Biological Laboratories Co., Ltd. were plated onto 96-well culture plates at a density of 2000 cells/well, a designated concentration of MEK inhibitor 24 (RO4987655) was added, and the cells were incubated for 4 days. On the 4th day of culture, a solution of Cell Counting Kit-8 was added, and absorbance (measurement wavelength: 450 nm; reference wavelength: 630 nm) was measured according to the protocol attached to the kit, and 50% inhibitory concentration (IC50) was calculated.

Name

Type

Language

RO-4987655

Common Name

English

RO 4987655 [WHO-DD]

Common Name

English

RO4987655

Code

English

CH-4987655

Code

English

Code System Code Type Description

SMS_ID

100000178250