Drug Information

Drug (ID: DG00642) and It's Reported Resistant Information
Name
PLX51107
Synonyms
PLX51107; 1627929-55-8; (S)-4-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid; PLX-51107; PLX 51107; UNII-W758F1L9ND; BRD4 inhibitor PLX51107; W758F1L9ND; 4-{6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1S)-1-(pyridin-2-yl)ethyl]-1H-pyrrolo[3,2-b]pyridin-3-yl}benzoic acid; 4-(6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-((1S)-1-pyridin-2-ylethyl)pyrrolo(3,2-b)pyridin-3-yl)benzoic acid; 4-[6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1S)-1-pyridin-2-ylethyl]pyrrolo[3,2-b]pyridin-3-yl]benzoic acid; CHEMBL4521078; SCHEMBL16085681; BDBM425592; CQC92955; EX-A1824; PLX 51107 [WHO-DD]; PXL51107; MFCD31657388; NSC806595; s8739; AKOS037648775; NSC-806595; US10519177, Compound P-0511; AC-32941; BS-15563; HY-111422; CS-0040568; D80522; A930121; 4-[6-(3,5-dimethylisoxazol-4-yl)-1- [(1S)-1-(2-pyridyl)ethyl]pyrrolo[3,2- b]pyridin-3-yl]benzoic acid; 4-[6-(3,5-dimethylisoxazol-4-yl)-1-[(1S)-1-(2-pyridyl)ethyl]pyrrolo[3,2-b]pyridin-3-yl]benzoic acid; 6JF; Benzoic acid, 4-(6-(3,5-dimethyl-4-isoxazolyl)-1-((1S)-1-(2-pyridinyl)ethyl)-1H-pyrrolo(3,2-b)pyridin-3-yl)-
    Click to Show/Hide
Indication
In total 2 Indication(s)
Melanoma [ICD-11: 2C30]
Investigative
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Investigative
[1]
Structure
Target Serine/threonine-protein kinase B-raf (BRAF) BRAF_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C26H22N4O3
IsoSMILES
CC1=C(C(=NO1)C)C2=CC3=C(C(=CN3[C@@H](C)C4=CC=CC=N4)C5=CC=C(C=C5)C(=O)O)N=C2
InChI
1S/C26H22N4O3/c1-15-24(17(3)33-29-15)20-12-23-25(28-13-20)21(18-7-9-19(10-8-18)26(31)32)14-30(23)16(2)22-6-4-5-11-27-22/h4-14,16H,1-3H3,(H,31,32)/t16-/m0/s1
InChIKey
AMSUHYUVOVCWTP-INIZCTEOSA-N
PubChem CID
90448953
TTD Drug ID
D05HTS
DrugBank ID
DB16038
Type(s) of Resistant Mechanism of This Drug
  DISM: Drug Inactivation by Structure Modification
  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
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Superoxide dismutase Mn (SODM) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model Omm1.3 cells Skin Homo sapiens (Human) N.A.
92.1 cells Peripheral blood Homo sapiens (Human) N.A.
UM004 cells Skin Homo sapiens (Human) N.A.
Omm1 cells Kidney Homo sapiens (Human) CVCL_6939
In Vivo Model Athymic nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Western blotting assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Both assays showed higher expression of these genes(REL, RELB, CEBPD, SOD2) at the mRNA and protein level in the resistant cells compared with their parental counterpart. Furthermore, NF-kappa-B activity was increased in the resistant cells compared with parental, and it could be inhibited by PTL.Inhibition of NF-kappa-B-dependent signaling enhances sensitivity and overcomes resistance to BET inhibition in uveal melanoma.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: RELB proto-oncogene, NF-kB subunit (RELB) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model Omm1.3 cells Skin Homo sapiens (Human) N.A.
92.1 cells Peripheral blood Homo sapiens (Human) N.A.
UM004 cells Skin Homo sapiens (Human) N.A.
Omm1 cells Kidney Homo sapiens (Human) CVCL_6939
In Vivo Model Athymic nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Western blotting assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Both assays showed higher expression of these genes(REL, RELB, CEBPD, SOD2) at the mRNA and protein level in the resistant cells compared with their parental counterpart. Furthermore, NF-kappa-B activity was increased in the resistant cells compared with parental, and it could be inhibited by PTL.Inhibition of NF-kappa-B-dependent signaling enhances sensitivity and overcomes resistance to BET inhibition in uveal melanoma.
Key Molecule: REL proto-oncogene, NF-kB subunit (REL) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model Omm1.3 cells Skin Homo sapiens (Human) N.A.
92.1 cells Peripheral blood Homo sapiens (Human) N.A.
UM004 cells Skin Homo sapiens (Human) N.A.
Omm1 cells Kidney Homo sapiens (Human) CVCL_6939
In Vivo Model Athymic nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Western blotting assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Both assays showed higher expression of these genes(REL, RELB, CEBPD, SOD2) at the mRNA and protein level in the resistant cells compared with their parental counterpart. Furthermore, NF-kappa-B activity was increased in the resistant cells compared with parental, and it could be inhibited by PTL.Inhibition of NF-kappa-B-dependent signaling enhances sensitivity and overcomes resistance to BET inhibition in uveal melanoma.
Key Molecule: CCAAT enhancer binding protein delta (CEBPD) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model Omm1.3 cells Skin Homo sapiens (Human) N.A.
92.1 cells Peripheral blood Homo sapiens (Human) N.A.
UM004 cells Skin Homo sapiens (Human) N.A.
Omm1 cells Kidney Homo sapiens (Human) CVCL_6939
In Vivo Model Athymic nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Western blotting assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Both assays showed higher expression of these genes(REL, RELB, CEBPD, SOD2) at the mRNA and protein level in the resistant cells compared with their parental counterpart. Furthermore, NF-kappa-B activity was increased in the resistant cells compared with parental, and it could be inhibited by PTL.Inhibition of NF-kappa-B-dependent signaling enhances sensitivity and overcomes resistance to BET inhibition in uveal melanoma.
References
Ref 1 Inhibition of NF-kB-Dependent Signaling Enhances Sensitivity and Overcomes Resistance to BET Inhibition in Uveal Melanoma .Cancer Res. 2019 May 1;79(9):2415-2425. doi: 10.1158/0008-5472.CAN-18-3177. Epub 2019 Mar 18. 10.1158/0008-5472.CAN-18-3177

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Zhang.