Drug Information

Drug (ID: DG01518) and It's Reported Resistant Information

Name	RO4927350
Synonyms	876755-27-0; RO4927350; Ro 4927350; (2S,3S)-2-((R)-4-(4-(2-hydroxyethoxy)phenyl)-2,5-dioxoimidazolidin-1-yl)-3-phenyl-N-(4-propionylthiazol-2-yl)butanamide.; SCHEMBL1204725; CHEMBL2396994; CHEBI:132984; ZINC43203214; RO-4927350; (2S,3S)-2-[(4R)-4-[4-(2-hydroxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]-3-phenyl-N-(4-propanoyl-1,3-thiazol-2-yl)butanamide; (2S,3S)-2-{(4R)-4-[4-(2-hydroxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propionyl-1,3-thiazol-2-yl)butanamide; (2s,3s)-2-{(r)-4-[4-(2-hydroxy-ethoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-n-(4-propionyl-thiazol-2-yl)-butyramide Click to Show/Hide
Structure
Target	.	NOUNIPROTAC	[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula	11
IsoSMILES	CCC(=O)C1=CSC(=N1)NC(=O)[C@H]([C@@H](C)C2=CC=CC=C2)N3C(=O)[C@H](NC3=O)C4=CC=C(C=C4)OCCO
InChI	InChI=1S/C27H28N4O6S/c1-3-21(33)20-15-38-26(28-20)30-24(34)23(16(2)17-7-5-4-6-8-17)31-25(35)22(29-27(31)36)18-9-11-19(12-10-18)37-14-13-32/h4-12,15-16,22-23,32H,3,13-14H2,1-2H3,(H,29,36)(H,28,30,34)/t16-,22+,23-/m0/s1
InChIKey	RKKBPPTYPGTSEA-FNVCAUGXSA-N
PubChem CID	11526671

Type(s) of Resistant Mechanism of This Drug

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Click to Show/Hide the Resistance Disease of This Class

Colorectal cancer [ICD-11: 2B91]

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: MAPK/ERK kinase 1 (MEK1)				[1]
Molecule Alteration	Missense mutation		p.F129L (c.385T>C)	Molecule Info
Sensitive Disease	Colorectal cancer [ICD-11: 2B91.1]			Disease Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	HT-29 cells	Colon	Homo sapiens (Human)	CVCL_0320
In Vivo Model	Mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the sensitivity of RO4927350 by unusual activation of pro-survival pathway

References

Ref 1	Identification of the MEK1(F129L) activating mutation as a potential mechanism of acquired resistance to MEK inhibition in human cancers carrying the B-RafV600E mutationCancer Res. 2011 Aug 15;71(16):5535-45. doi: 10.1158/0008-5472.CAN-10-4351. Epub 2011 Jun 24.