RAVOXERTINIB BESYLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H18ClFN6O2.C6H6O3S
Molecular Weight	599.033
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(=O)(=O)C1=CC=CC=C1.CN2N=CC=C2NC3=NC(=CC=N3)C4=CC(=O)N(C=C4)[C@H](CO)C5=CC=C(Cl)C(F)=C5

InChI

InChIKey=TWSFAQBOAWKKIH-GMUIIQOCSA-N

InChI=1S/C21H18ClFN6O2.C6H6O3S/c1-28-19(5-8-25-28)27-21-24-7-4-17(26-21)13-6-9-29(20(31)11-13)18(12-30)14-2-3-15(22)16(23)10-14;7-10(8,9)6-4-2-1-3-5-6/h2-11,18,30H,12H2,1H3,(H,24,26,27);1-5H,(H,7,8,9)/t18-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C21H18ClFN6O2
Molecular Weight	440.858
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C6H6O3S
Molecular Weight	158.175
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.arraybiopharma.com/product-pipeline/other-compounds/gdc-0994/
Curator's Comment: description was created based on several sources, including: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3404&sKey=1eb84585-6831-405d-88b2-cef74aaf004e&cKey=22cc177f-4718-4f12-bdf6-a275db718f29&mKey=6ffe1446-a164-476a-92e7-c26446874d93 | https://www.ncbi.nlm.nih.gov/pubmed/27227380

GDC-0994 (RG7842) is a selective inhibitor of ERK1/2, also known as extracellular-signal-regulated kinases. Daily, oral dosing of GDC-0994 results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice. GDC-0994 neither increases nor decreases phospho-ERK, suggesting that different ERK inhibitors have alternative mechanisms of action with respect to feedback signaling. GDC-0994 is currently advancing in a Phase 1 trial in patients with solid tumors.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
MAP kinase ERK1 5 Target ID: CHEMBL3385 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27227380	Inhibitor 8297		6.1 nM [IC50]
MAP kinase ERK2 7 Target ID: CHEMBL4040 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27227380	Inhibitor 8297		3.1 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: http://www.arraybiopharma.com/product-pipeline/other-compounds/gdc-0994/ http://adisinsight.springer.com/drugs/800038284	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
10.7 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	800 mg 1 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.66 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.68 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.17 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.57 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.88 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
179 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	800 mg 1 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
26.8 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
62 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
88.9 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
129 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
27.7 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31848189/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAVOXERTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00AC0V	https://www.1pchem.com/search?query=1P00AC0V
1PlusChem LLC	1P01EONZ	https://www.1pchem.com/search?query=1P01EONZ
AChemBlock	10339	http://www.achemblock.com/catalogsearch/result/?q=10339
AChemBlock	K12413	http://www.achemblock.com/catalogsearch/result/?q=K12413
AK Scientific	2428AH	https://aksci.com/item_detail.php?cat=2428AH
AOBIOUS INC	AOB87103	http://aobious.com/aobious/search?search_query=AOB87103
ApexBio Technology	B5817	https://www.apexbt.com/catalogsearch/result/?q=B5817
AstaTech	42237	http://astatechinc.com/CPSResult.php?CRNO=42237
BLD Pharm	BD330001	http://www.bldpharm.com/search/Search.html?keyword=BD330001
Cayman Chemical	21107	http://www.caymanchem.com/app/template/Product.vm/catalog/21107
Chem Scene	CS-3704	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3704
Chem Scene	CS-5092	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5092
ChemShuttle	140501	https://www.chemshuttle.com/catalogsearch/result/?q=140501
Combi-Blocks	QJ-7929	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-7929
Debye Scientific	DA-33607	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-33607
KeyOrganics	AS-55994	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-55994
MedChem Express	HY-15947	https://www.medchemexpress.com/search.html?q=HY-15947A&ft=&fa=&fp=
MedChem Express	HY-15947A	https://www.medchemexpress.com/search.html?q=HY-15947A&ft=&fa=&fp=
MolPort	MolPort-035-789-688	https://www.molport.com/shop/molecule-link/MolPort-035-789-688
MolPort	MolPort-046-418-261	https://www.molport.com/shop/molecule-link/MolPort-046-418-261
Molnova	M11952	https://www.molnova.com/en/serch-list.html?keywords=M11952
MuseChem	I001753	https://www.musechem.com/product/I001753.html
ShangHai Biochempartner	BCP001166	http://www.biochempartner.com/search_BCP001166
ShangHai Biochempartner	BCP09668	http://www.biochempartner.com/search_BCP09668
ShangHai Biochempartner	BCP20235	http://www.biochempartner.com/search_BCP20235
TargetMol	T6511	https://www.targetmol.com/search?keyword=T6511
eMolecules	195078444	https://orderbb.emolecules.com/search/#?query=195078444
eMolecules	195316723	https://orderbb.emolecules.com/search/#?query=195316723
eMolecules	301155295	https://orderbb.emolecules.com/search/#?query=301155295
eMolecules	50241530	https://orderbb.emolecules.com/search/#?query=50241530
eMolecules	72973236	https://orderbb.emolecules.com/search/#?query=72973236
mcule	MCULE-3184544600	https://mcule.com/MCULE-3184544600/
mcule	MCULE-5091849098	https://mcule.com/MCULE-5091849098/
mcule	MCULE-7378954480	https://mcule.com/MCULE-7378954480/
mcule	MCULE-8345183636	https://mcule.com/MCULE-8345183636/
mcule	MCULE-9201399591	https://mcule.com/MCULE-9201399591/

PubMed

Title	Date	PubMed
Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development.	2016 Jun 23	27227380

Patents

Sample Use Guides

In Vivo Use Guide

Once daily on a 21-day on/7 day off schedule. Dose from 50 to 200 mg

Route of Administration: Oral

In Vitro Use Guide

GDC-0994 inhibits the ERK-dependent p90RSK Serine 380 phosphorylation in PMA-stimulated HepG2 cells (IC50=12nM).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:24:09 UTC 2023` Edited by `admin` on `Sat Dec 16 09:24:09 UTC 2023`
Record UNII	TMG3621R53
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

RAVOXERTINIB BESYLATE

Common Name

English

BENZENESULFONIC ACID, COMPD. WITH 1-((1S)-1-(4-CHLORO-3-FLUOROPHENYL)-2-HYDROXYETHYL)-4-(2-((1-METHYL-1H-PYRAZOL-5-YL)AMINO)-4-PYRIMIDINYL)-2(1H)-PYRIDINONE (1:1)

Systematic Name

English

Code System Code Type Description

PUBCHEM

91971355

Created by admin on Sat Dec 16 09:24:09 UTC 2023 , Edited by admin on Sat Dec 16 09:24:09 UTC 2023

PRIMARY

CAS

1817728-45-2

Created by admin on Sat Dec 16 09:24:09 UTC 2023 , Edited by admin on Sat Dec 16 09:24:09 UTC 2023

PRIMARY

FDA UNII

TMG3621R53

Created by admin on Sat Dec 16 09:24:09 UTC 2023 , Edited by admin on Sat Dec 16 09:24:09 UTC 2023

PRIMARY

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					R6AXV96CRH

RAVOXERTINIB

PARENT -> SALT/SOLVATE

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					R6AXV96CRH

RAVOXERTINIB

ACTIVE MOIETY

Details

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

Sourcing

PubMed

Patents

Sample Use Guides

C_max