CC-90003 - ≥98% , CAS No.1621999-82-3

CAS: 1621999-82-3 Cat. No.: C414190 Molecular Weight: 458.44

GRADE & PURITY ≥98%

Synonyms

2-​Propenamide,N-​[2-​[[2-​[(2-​methoxy-​5-​methyl-​4-​pyridinyl)​amino]​-​5-​(trifluoromethyl)​-​4-​pyrimidinyl]​amino]​-​5-​methylphenyl]​-

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

CC-90003 CC-90003 is an irreversible inhibitor of ERK1/2 with IC50s in the 10-20 nM range and shows good kinase selectivity in a 258-kinase biochemical assay.

Targets

ERK1 ; ERK2

In vitro

In biochemical, cellular, and mass spectrometry assays of 347 kinases, CC-90003 was found to strongly inhibit kinase activities of ERK1 and ERK2 with IC50s in the 10 to 20 nmol/L range and had good kinase selectivity. In a 258-kinase biochemical assay panel, significant inhibition of 213 kinases (<50% inhibition), moderate inhibition of 28 kinases (50%–80% inhibition), and >80% inhibition of 17 kinases by CC-90003 were found. In an ActivX cellular kinase screening using A375 BRAF V600E-mutant melanoma cell line, only 5 of 194 kinases (ERK1, ERK2, MKK4, MKK6, and FAK) were inhibited by >80% at 1 mmol/L of CC-90003. At the same concentration, no significant inhibition (<14%) was found in a Cerep panel of 40 nonkinase enzymes and receptors. Through our iterative analyses, only 3 kinases, in addition to ERK1/2, were inhibited in cells at biologically relevant concentrations: KDR, FLT3, and PDGFRa. Tumors with BRAF mutations were particularly sensitive to CC-90003. In many, but not all cases, CC-90003 had cytotoxic effects in KRAS-mutant PDAC, lung cancer, and colorectal cancer cell lines. CC-90003 does not significantly inhibit proliferation of normal lung fibroblasts or bronchial epithelial cells.

In vivo

In in vivo studies of an HCT-116 xenograft model, CC-90003 was well tolerated at a range of doses (12.5 mg b.i.d.-100 mg qd), although doses of 50 mpk b.i.d. and 75 mpk b.i.d. group caused mortality by days 6 to 18 of study. Both dosing schedules (qd and b.i.d.) leads to tumor growth inhibition. CC-90003 inhibits tumor growth in vivo of three KRAS-mutant PDX models.

Cell Research(from reference)

Cell lines：KRAS-mutant cell lines 

Incubation Time：72 h 

Specifications

Synonyms

2-​Propenamide, N-​[2-​[[2-​[(2-​methoxy-​5-​methyl-​4-​pyridinyl)​amino]​-​5-​(trifluoromethyl)​-​4-​pyrimidinyl]​amino]​-​5-​methylphenyl]​-

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

CC-90003 is an irreversible inhibitor of ERK1/2 with IC50s in the 10-20 nM range and shows good kinase selectivity in a 258-kinase biochemical assay.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Purity

≥98%

Product Properties

• ALogP: 5.316
• hba_count: 5
• HBD Count: 3
• Rotatable Bond: 8

Names and Identifiers

• Pubchem Sid: 504772575
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504772575
• Canonical Smiles: CC1=CC(=C(C=C1)NC2=NC(=NC=C2C(F)(F)F)NC3=CC(=NC=C3C)OC)NC(=O)C=C
• IUPAC Name: N-[2-[[2-[(2-methoxy-5-methylpyridin-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]-5-methylphenyl]prop-2-enamide
• InChIKey: ILUKRINUNLAVMH-UHFFFAOYSA-N
• INCHI: 1S/C22H21F3N6O2/c1-5-18(32)28-17-8-12(2)6-7-15(17)29-20-14(22(23,24)25)11-27-21(31-20)30-16-9-19(33-4)26-10-13(16)3/h5-11H,1H2,2-4H3,(H,28,32)(H2,26,27,29,30,31)
• Isomeric SMILES: CC1=CC(=C(C=C1)NC2=NC(=NC=C2C(F)(F)F)NC3=CC(=NC=C3C)OC)NC(=O)C=C
• Molecular Weight: 458.44
• Reaxy-Rn: 27064513
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=27064513&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Anilides

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Anilides
• Intermediate Tree Nodes: Not available
• Direct Parent: Anilides
• Alternative Parents: Diaminotoluenes Aniline and substituted anilines N-arylamides Alkyl aryl ethers Aminopyridines and derivatives Aminopyrimidines and derivatives Methylpyridines Imidolactams Heteroaromatic compounds Acrylic acids and derivatives Secondary carboxylic acid amides Azacyclic compounds Organofluorides Carbonyl compounds Alkyl fluorides Hydrocarbon derivatives Amines Organic oxides
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Diaminotoluene - Anilide - N-arylamide - Aniline or substituted anilines - Alkyl aryl ether - Aminopyridine - Aminopyrimidine - Toluene - Methylpyridine - Pyridine - Pyrimidine - Imidolactam - Heteroaromatic compound - Acrylic acid or derivatives - Carboxamide group - Secondary carboxylic acid amide - Azacycle - Organoheterocyclic compound - Carboxylic acid derivative - Ether - Organofluoride - Organohalogen compound - Amine - Alkyl halide - Organic oxide - Carbonyl group - Hydrocarbon derivative - Organic oxygen compound - Organonitrogen compound - Organooxygen compound - Organic nitrogen compound - Alkyl fluoride - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

MAPK3 Tchem MAP kinase ERK1 (4725 Activities)

Discover Target: MAPK3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

Mapk1 MAP kinase ERK2 (650 Activities)

Discover Target: Mapk1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mechanisms of Action

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 92 mg/mL (200.68 mM); Water: Insoluble; Ethanol: Insoluble
• DMSO(mg / mL) Max Solubility: 92
• DMSO(mM) Max Solubility: 200.680568885787
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 458.400 g/mol
• XLogP3: 4.600
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 7
• Exact Mass: 458.168 Da
• Monoisotopic Mass: 458.168 Da
• Topological Polar Surface Area: 101.000 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 667.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1