Drug Information

Drug (ID: DG01478) and It's Reported Resistant Information
Name
Enzastaurin
Synonyms
Enzastaurin; 170364-57-5; Enzastaurin (LY317615); LY317615; 3-(1-Methyl-1H-indol-3-yl)-4-(1-(1-(pyridin-2-ylmethyl)piperidin-4-yl)-1H-indol-3-yl)-1H-pyrrole-2,5-dione; LY-317615; UNII-UC96G28EQF; 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione; UC96G28EQF; LY 317615; CHEMBL300138; DB102; DSSTox_CID_24029; DSSTox_RID_80101; DSSTox_GSID_44029; 3-(1-Methyl-1H-indol-3-yl)-4-(1-(1-(pyridin-2-ylmethyl)-piperidin-4-yl)-1H-indol-3-yl)-1H-pyrrole-2,5-dione; C32H29N5O2; 3-(1-Methyl-1H-indol-3-yl)-4-(1-(1-(2-pyridinylmethyl)-4-piperidinyl)-1H-indol-3-yl)-1H-pyrrole-2,5-dione; 3-(1-methyl-1H-indol-3-yl)-4-{1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1H-indol-3-yl}-1H-pyrrole-2,5-dione; CAS-170364-57-5; 3-(1-Methyl-1H-indol-3-yl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione; LE-0014; Enzastaurin [USAN:INN]; Enzastaurin,LY317615; Enzastaurin; LY317615; LY317615 - Enzastaurin; SCHEMBL678748; GTPL5693; DTXSID5044029; CHEBI:91368; AMY7827; BCPP000241; HMS3265M05; HMS3265M06; HMS3265N05; HMS3265N06; HMS3654A13; HMS3748E03; BCP02703; EX-A1055; WHO 8426; ZINC1494900; Tox21_113367; BDBM50128285; DB-102; MFCD11040980; NSC767124; NSC800096; s1055; AKOS015994764; Tox21_113367_1; AC-5900; BCP9000648; CCG-264797; CS-0132; DB06486; NSC-767124; NSC-800096; SB16481; NCGC00238452-01; NCGC00238452-02; NCGC00238452-03; NCGC00238452-11; HY-10342; DB-064781; FT-0667873; SW219797-1; W3715; EC-000.2315; 364E575; J-510442; Q5381479; BRD-K79404599-001-01-0; 1H-Pyrrole-2,5-dione, 3-(1-methyl-1H-indol-3-yl)-4-(1-(1-(2-pyridinylmethyl)-4-piperidinyl)-1H-indol-3-yl)-; 3-(1-Methyl-1H-indol-3-yl)-4-(1-(1-(2-pyridinylmethyl)-4-piperidinyl)-1H-indol-3-yl)-1H-pyrrole-2,5-; 3-(1-Methyl-1H-indol-3-yl)-4-[1-(1-pyridin-2-ylmethyl-piperidin-4-yl)-1H-indol-3-yl]-pyrrole-2,5-dione; 3-(1-methyl-1H-indol-3-yl)-4-{1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1H-indol-3-yl}-2,5-dihydro-1H-pyrrole-2,5-dione
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Indication
In total 1 Indication(s)
Convulsion [ICD-11: 8A61-8A6Z]
Phase 3
[1]
Structure
Target Fungal 1,3-beta-glucan synthase (Fung GSC2) FKS2_YEAST [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
5
IsoSMILES
CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=CN(C5=CC=CC=C54)C6CCN(CC6)CC7=CC=CC=N7
InChI
InChI=1S/C32H29N5O2/c1-35-19-25(23-9-2-4-11-27(23)35)29-30(32(39)34-31(29)38)26-20-37(28-12-5-3-10-24(26)28)22-13-16-36(17-14-22)18-21-8-6-7-15-33-21/h2-12,15,19-20,22H,13-14,16-18H2,1H3,(H,34,38,39)
InChIKey
AXRCEOKUDYDWLF-UHFFFAOYSA-N
PubChem CID
176167
ChEBI ID
CHEBI:91368
TTD Drug ID
D0F9BY
VARIDT ID
DR1898
DrugBank ID
DB06486
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
Uveal melanoma [ICD-11: 2D0Y]
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: Guanine nucleotide-binding protein alpha-q (GNAQ) [1]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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10
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30
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80
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90
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110
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120
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130
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D
D
A
A
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P
140
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G
G
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C
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150
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E
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Y
Y
160
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L
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D
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A
A
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170
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A
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L
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180
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F
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E
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V
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F
L
L
230
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A
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240
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250
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260
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N
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270
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I
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F
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L
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280
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300
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310
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L
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350
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L
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N
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L
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E
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N
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L
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V
V
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ocm3 cells Skin Homo sapiens (Human) CVCL_6937
Ocm1 cells Hypodermis Homo sapiens (Human) CVCL_6934
Mum2C cells Hypodermis Homo sapiens (Human) CVCL_3448
Mum2B cells Uveal melanoma Homo sapiens (Human) CVCL_3447
M619 cells Skin Homo sapiens (Human) CVCL_8472
C918 cells Skin Homo sapiens (Human) CVCL_8471
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.Q209L (c.626A>T) in gene GNAQ cause the sensitivity of Enzastaurin by unusual activation of pro-survival pathway
Key Molecule: Guanine nucleotide-binding protein alpha-q (GNAQ) [1]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209P (c.626A>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ocm3 cells Skin Homo sapiens (Human) CVCL_6937
Ocm1 cells Hypodermis Homo sapiens (Human) CVCL_6934
Mum2C cells Hypodermis Homo sapiens (Human) CVCL_3448
Mum2B cells Uveal melanoma Homo sapiens (Human) CVCL_3447
M619 cells Skin Homo sapiens (Human) CVCL_8472
C918 cells Skin Homo sapiens (Human) CVCL_8471
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.Q209P (c.626A>C) in gene GNAQ cause the sensitivity of Enzastaurin by unusual activation of pro-survival pathway
References
Ref 1 The protein kinase C inhibitor enzastaurin exhibits antitumor activity against uveal melanomaPLoS One. 2012;7(1):e29622. doi: 10.1371/journal.pone.0029622. Epub 2012 Jan 12.

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