10mM in DMSO for sensitive chromatographic and analytical workflows requiring minimal baseline interference.
Store at -80°C Ships Dry ice packs + Cold packs Check lot-specific COA for exact specifications.
SDS, COA, datasheet, and spec sheet available for download. Lot-specific COA accessible via lot number lookup.
Cited in 0 peer-reviewed publications across chromatography, organic synthesis, and cross-coupling reactions.
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 KRASG12C 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 KRASG12C 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 KRASG12C 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 KRASG12V. KRASG12C 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-KRASG12C cells at concentrations up to 10-fold higher than its KRASG12C 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 KRASG12C but not in those expressing KRASG12C/A59G. ARS853 traps KRASG12C 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
| Canonical Smiles | CC1(CC1)C2=CC(=C(C=C2Cl)O)NCC(=O)N3CCN(CC3)C4CN(C4)C(=O)C=C |
|---|---|
| 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 |
| InChIKey | IPFOCHMOYUMURK-UHFFFAOYSA-N |
| 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 |
| 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= |
Comprehensive hazard, handling, storage, and regulatory compliance document.
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View spec sheet →Taxonomy Tree
| 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 |
| 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 Ų |
| 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 |
