Drug Information

Drug (ID: DG01248) and It's Reported Resistant Information
Name
Entrectinib
Synonyms
Entrectinib; 1108743-60-7; NMS-E628; RXDX-101; Rozlytrek; UNII-L5ORF0AN1I; Entrectinib (RXDX-101); Entrectinib(rxdx-101); L5ORF0AN1I; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide; N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide; N-{5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl}-4-(4-methylpiperazin-1-yl)-2-[(oxan-4-yl)amino]benzamide; Benzamide, N-(5-((3,5-difluorophenyl)methyl)-1H-indazol-3-yl)-4-(4-methyl-1-piperazinyl)-2-((tetrahydro-2H-pyran-4-yl)amino)-; Benzamide, N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methyl-1-piperazinyl)-2-[(tetrahydro-2H-pyran-4-yl)amino]-; Entrectinib [USAN:INN]; Rozlytrek (TN); YMX; Entrectinib, 95%; Kinome_2659; Entrectinib; NMS-E628; Entrectinib (JAN/USAN/INN); GTPL8290; SCHEMBL3512601; CHEMBL1983268; NMS-E-628; NMS-E628;RXDX-101; HMS3886H21; BCP16174; EX-A2261; MFCD28129099; NSC774769; NSC800095; s7998; ZINC43204146; CCG-270048; DB11986; NSC-774769; NSC-800095; SB17194; NCGC00484067-01; NCGC00484067-02; NCGC00484067-03; AC-31286; AS-75092; DA-47850; HY-12678; N-(5-(3,5-Difluorobenzyl)-1H-indazol-3-yl)-4-(4-methylpiperazin-1yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; B5859; FT-0736318; D10926; A856078; Q25323953; S900006830; RXDX101; RXDX 101; RXDX-101; NMS E628; NMS-E628;NMS E628; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-methyl-1-piperazinyl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-Difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide; N-{5-[(3,5-difluorophenyl)methyl]-3H-indazol-3-ylidene}-4-(4-methylpiperazin-1-yl)-2-[(oxan-4-yl)amino]benzamide
    Click to Show/Hide
Indication
In total 7 Indication(s)
Colorectal cancer [ICD-11: 2B91]
Approved
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Patented
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1
[1]
Colorectal cancer [ICD-11: 2B91]
Investigative
[1]
Mammary analogue secretory carcinoma [ICD-11: 2C60-2C6Y]
Investigative
[1]
Neuroblastoma [ICD-11: 2A00]
Investigative
[1]
Non-small cell lung cancer [ICD-11: 2C25]
Investigative
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Brain cancer [ICD-11: 2A00]
[2]
Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
Breast cancer [ICD-11: 2C60]
[1]
Breast lactating adenoma [ICD-11: 2F30]
[1]
Colorectal cancer [ICD-11: 2B91]
[3]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C31H34F2N6O2
IsoSMILES
CN1CCN(CC1)C2=CC(=C(C=C2)C(=O)NC3=NNC4=C3C=C(C=C4)CC5=CC(=CC(=C5)F)F)NC6CCOCC6
InChI
1S/C31H34F2N6O2/c1-38-8-10-39(11-9-38)25-3-4-26(29(19-25)34-24-6-12-41-13-7-24)31(40)35-30-27-17-20(2-5-28(27)36-37-30)14-21-15-22(32)18-23(33)16-21/h2-5,15-19,24,34H,6-14H2,1H3,(H2,35,36,37,40)
InChIKey
HAYYBYPASCDWEQ-UHFFFAOYSA-N
PubChem CID
25141092
TTD Drug ID
D0H6JK
INTEDE ID
DR0582
DrugBank ID
DB11986
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
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 Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tropomyosin-related kinase A (TrkA) [3]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G595R (c.1783G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5H3Q
Mutant Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 8J5X
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.34
TM score: 0.93325
Amino acid change:
G595R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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510
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520
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530
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540
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550
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560
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570
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580
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590
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600
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610
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620
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630
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640
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650
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660
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670
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680
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690
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W
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700
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710
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720
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730
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740
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750
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760
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770
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780
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790
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model KM-12 cells Colon Homo sapiens (Human) CVCL_1331
In Vivo Model NOD-SCID mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 ddPCR; Kinase domain alignment assay
References
Ref 1 What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC) .Ann Oncol. 2016 May;27(5):920-6. doi: 10.1093/annonc/mdw042. Epub 2016 Feb 15. 10.1093/annonc/mdw042
Ref 2 ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models. Cell Rep. 2024 Oct 22;43(10):114829.
Ref 3 Acquired Resistance to the TRK Inhibitor Entrectinib in Colorectal CancerCancer Discov. 2016 Jan;6(1):36-44. doi: 10.1158/2159-8290.CD-15-0940. Epub 2015 Nov 6.

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