Basic Description

Synonyms	2-Propen-1-one,1-[3-[4-[2-[[4-chloro-2-hydroxy-5-(1-methylcyclopropyl)phenyl]amino]acetyl]-1-piperazinyl]-1-azetidinyl]-
Specifications & Purity	≥95%
Biochemical and Physiological Mechanisms	ARS-853 is a selective, covalent KRAS(G12C) inhibitor that inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation. ARS-853 also induces apoptosis.
Storage Temp	Store at -20°C
Shipped In	Ice chest + Ice pads This product requires cold chain shipping. Ground and other economy services are not available.
Product Description	Information ARS-853 (ARS853) ARS-853 is a selective, covalent KRAS(G12C) inhibitor that inhibits mutant KRAS-driven signaling by binding to the GDP-bound oncoprotein and preventing activation. ARS-853 also induces apoptosis . Targets K-Ras(G12C) (in H358 cells) 2.5 μM In vitro ARS-853 treatment of KRAS^G12C cells led to a dose-dependent and nearly complete inhibition of CRAF-RBD (RBD)-mediated pulldown of KRAS from lysates, with an IC50 of approximately 1 μmol/L. Treatment of H358 cells by ARS-853 resulted in a significant loss of KRAS–CRAF interactions. Consistent with an inactive state of KRAS^G12C once bound to ARS-853, downstream signaling through both MAPK (including pMEK, pERK, and pRSK) and PI3K signaling (pAKT) pathways was inhibited by ARS-853 in H358 and other KRAS^G12C cell lines. The inhibition of RAF-RBD pulldown and KRAS downstream signaling was sustained over a period of 72 hours, accompanied by G1 cell-cycle arrest, loss of Cyclin D1 and Rb expression, and an increase in the cell-cycle inhibitor p27 KIP1. In addition, hallmarks of apoptosis, including cleaved PARP and increases in sub-diploid DNA, were observed in H358 cells following treatment with ARS-853. No effects on RAF-RBD binding or downstream signaling were observed in A549 cells (KRASG12S), and the inhibitory effects of ARS-853 in H358 cells could be rescued by ectopic expression of KRAS^G12V. KRAS^G12C is the most potent covalent target of ARS-853 across more than 2,700 cellular proteins and consistently find that this compound exerts no effects on cellular signaling or growth in non-KRAS^G12C cells at concentrations up to 10-fold higher than its KRAS^G12C potency. ARS-853 reacts only with the inactive (GDP-bound), but the not the active (GTP-bound), state of KRAS. ARS853 reduced KRAS-GTP levels and ERK phosphorylation in human embryonic kidney 293 (HEK293) or H358 cells engineered to express KRAS^G12C but not in those expressing KRAS^G12C/A59G. ARS853 traps KRAS^G12C in a GDP-bound conformation by lowering its affinity for nucleotide exchange factors. Cell Research(from reference) Cell lines：H358 (G12C) cells Concentrations：0.05, 0.1, 0.5, 1, 5, 10, 50 μM Incubation Time：5 h

Taxonomic Classification

Taxonomy Tree

Kingdom Organic compounds
- Superclass Organic acids and derivatives
  - Class Carboxylic acids and derivatives
    - Subclass Amino acids, peptides, and analogues
      - Level5 Amino acids and derivatives
        Level6 Alpha amino acids and derivatives
        Level7 Alpha amino acid amides

Kingdom	Organic compounds
Superclass	Organic acids and derivatives
Class	Carboxylic acids and derivatives
Subclass	Amino acids, peptides, and analogues
Intermediate Tree Nodes	Amino acids and derivatives - Alpha amino acids and derivatives
Direct Parent	Alpha amino acid amides
Alternative Parents	o-Aminophenols Phenylalkylamines Aniline and substituted anilines M-chlorophenols Secondary alkylarylamines 1-hydroxy-2-unsubstituted benzenoids N-alkylpiperazines Chlorobenzenes Aryl chlorides Tertiary carboxylic acid amides Acrylic acids and derivatives Trialkylamines Azetidines Azacyclic compounds Organopnictogen compounds Hydrocarbon derivatives Organic oxides Organochlorides Carbonyl compounds
Molecular Framework	Aromatic heteromonocyclic compounds
Substituents	Alpha-amino acid amide - O-aminophenol - Aminophenol - 3-halophenol - 3-chlorophenol - Aniline or substituted anilines - Phenylalkylamine - 1-hydroxy-2-unsubstituted benzenoid - Chlorobenzene - Halobenzene - Phenol - Secondary aliphatic/aromatic amine - N-alkylpiperazine - Aryl halide - Aryl chloride - Piperazine - Benzenoid - Monocyclic benzene moiety - 1,4-diazinane - Tertiary carboxylic acid amide - Acrylic acid or derivatives - Tertiary aliphatic amine - Tertiary amine - Azetidine - Carboxamide group - Secondary amine - Azacycle - Organoheterocyclic compound - Hydrocarbon derivative - Organic nitrogen compound - Amine - Organic oxygen compound - Carbonyl group - Organopnictogen compound - Organohalogen compound - Organochloride - Organonitrogen compound - Organooxygen compound - Organic oxide - Aromatic heteromonocyclic compound
Description	This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
External Descriptors	Not available
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

Mechanisms of Action

Mechanism of Action	Action Type	target ID	Target Name	Target Type	Target Organism	Binding Site Name	References

Names and Identifiers

Pubchem Sid	504772479
Pubchem Sid Url	https://pubchem.ncbi.nlm.nih.gov/substance/504772479
IUPAC Name	1-[3-[4-[2-[4-chloro-2-hydroxy-5-(1-methylcyclopropyl)anilino]acetyl]piperazin-1-yl]azetidin-1-yl]prop-2-en-1-one
INCHI	InChI=1S/C22H29ClN4O3/c1-3-20(29)27-13-15(14-27)25-6-8-26(9-7-25)21(30)12-24-18-10-16(22(2)4-5-22)17(23)11-19(18)28/h3,10-11,15,24,28H,1,4-9,12-14H2,2H3
InChIKey	IPFOCHMOYUMURK-UHFFFAOYSA-N
Smiles	CC1(CC1)C2=CC(=C(C=C2Cl)O)NCC(=O)N3CCN(CC3)C4CN(C4)C(=O)C=C
Isomeric SMILES	CC1(CC1)C2=CC(=C(C=C2Cl)O)NCC(=O)N3CCN(CC3)C4CN(C4)C(=O)C=C
Molecular Weight	432.94
Reaxy-Rn	27200600
Reaxys-RN_link_address	https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=27200600&ln=

Certificates（CoA,COO,BSE/TSE and Analysis Chart)

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Analytical Chart:

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5 results found

Lot Number	Certificate Type	Date	Item
K2219141	Certificate of Analysis	Sep 13, 2022	A413921
K2219092	Certificate of Analysis	Sep 13, 2022	A413921
K2219093	Certificate of Analysis	Sep 13, 2022	A413921
K2219136	Certificate of Analysis	Sep 13, 2022	A413921
K2219091	Certificate of Analysis	Sep 13, 2022	A413921

Chemical and Physical Properties

Solubility	Solubility (25°C) In vitro DMSO: 86 mg/mL warmed with 50ºC Water: bath (198.64 mM); Ethanol: 7 mg/mL warmed with 50ºC Water: bath (16.16 mM); Water: Insoluble;
Molecular Weight	432.900 g/mol
XLogP3	2.900
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Exact Mass	432.193 Da
Monoisotopic Mass	432.193 Da
Topological Polar Surface Area	76.100 Å²
Heavy Atom Count	30
Formal Charge	0
Complexity	671.000
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

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SKU	Size	Availability	Price
A413921-1mg	1mg	3	$184.90
A413921-5mg	5mg	2	$478.90
A413921-10mg	10mg	2	$695.90
A413921-25mg	25mg	2	$1,392.90
A413921-50mg	50mg	2	$2,340.90

ARS-853 (ARS853) - 95% , high purity , CAS No.1629268-00-3