Drug Information

Drug (ID: DG01568) and It's Reported Resistant Information

Name	TAK-441
Synonyms	TAK-441; 1186231-83-3; UNII-CY3QT94KWP; CY3QT94KWP; CHEMBL2205230; 6-ethyl-N-[1-(2-hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-phenacyl-3-(2,2,2-trifluoroethoxy)pyrrolo[3,2-c]pyridine-2-carboxamide; TAK 441; GTPL8200; SCHEMBL1061476; BCP20946; BDBM50401323; NSC771858; ZINC43207688; NSC-771858; SB18887; LM2094; TAK441; TAK 441; Q27088929; 6-ethyl-N-(1-(2-hydroxyacetyl)piperidin-4-yl)-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide Click to Show/Hide
Indication	In total 1 Indication(s) Colorectal cancer [ICD-11: 2B91] Phase 1 [1]
Structure
Target	MAPK/ERK kinase kinase (MAP3K)	NOUNIPROTAC	[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula	9
IsoSMILES	CCC1=CC2=C(C(=C(N2C)C(=O)NC3CCN(CC3)C(=O)CO)OCC(F)(F)F)C(=O)N1CC(=O)C4=CC=CC=C4
InChI	InChI=1S/C28H31F3N4O6/c1-3-19-13-20-23(27(40)35(19)14-21(37)17-7-5-4-6-8-17)25(41-16-28(29,30)31)24(33(20)2)26(39)32-18-9-11-34(12-10-18)22(38)15-36/h4-8,13,18,36H,3,9-12,14-16H2,1-2H3,(H,32,39)
InChIKey	ZADWXQMNNVICKB-UHFFFAOYSA-N
PubChem CID	44187367
TTD Drug ID	D03CHM

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Smoothened homolog (SMO)				[1]
Sensitive Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]			Disease Info
Molecule Alteration	Missense mutation		p.D473H (c.1417G>C)	Molecule Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	NIH3T3 cells	Embryo	Homo sapiens (Human)	CVCL_0594
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	[3H]-TAK-441 radioligand membrane binding assay; Affinity selection-MS binding assay

References

Ref 1	Inhibition mechanism exploration of investigational drug TAK-441 as inhibitor against Vismodegib-resistant Smoothened mutantEur J Pharmacol. 2014 Jan 15;723:305-13. doi: 10.1016/j.ejphar.2013.11.014. Epub 2013 Nov 28.